Technical Data Report

for

GRAVIOLA
Annona muricata

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Graviola
Preprinted from Herbal Secrets of the Rainforest, 2nd edition, by Leslie Taylor Published and copyrighted by Sage Press, Inc. © 2002

Fam ily: Annonaceae Genus: Annona Species: muricata Synonyms: Annona macrocarpa, A. bonplandiana, A. cearensis, Guanabanus muricatus Common Names: Graviola, soursop, guanábana, guanábano, guanavana, guanaba, corossol épineux, huanaba, toge-banreisi, durian benggala, nangka blanda, cachiman épineux Parts Used: Leaves, fruit, seeds, bark, roots

Graviola is a sm all, upright evergreen tree, 5–6 m high, with large, glossy, dark green leaves. It produces a large, heart-shaped, edible fruit that is 15–23 cm in diam eter, is yellow-green in color, and has white flesh inside. G raviola is indigenous to most of the warmest tropical areas in South and North America, including the Amazon. The fruit is sold in local markets in the tropics, where it is called guanábana in Spanish-speaking countries and graviola in Brazil. The fruit pulp is excellent for making drinks and sherbets and, though slightly sour-acid, can be eaten out of hand. All parts of the graviola tree are use d in natural medicine in the tropics, including the bark, leaves, roots, fruit, and fruit seeds. Different properties and uses are attributed to the different parts of the tree. Generally, the fruit and fruit juice are taken for worms and parasites, to cool fevers, as a lactagogue (to increase mother's m ilk after childbirth), and as an astringent for diarrhea and dysentery. The crushed seeds are used as a verm ifuge and anthelm intic against internal and external parasites, head lice, and worms. The bark, leaves, and roots are considered sedative, antispasmodic, hypotensive, and nervine, and a tea is made for various disorders toward those effects. Graviola has a long, rich history of use in herbal medicine as well as lengthy recorded indigenous use. In the Peruvian Andes, a leaf tea is used for catarrh (inflammation of mucous mem branes) and the crushed seed is used to kill parasites. In the Peruvian Amazon the bark, roots, and leaves are used for diabetes and as a sedative and antispasmodic. Indigenous tribes in Guyana use a leaf and/or bark tea as a sedative and heart tonic. In the Brazilian Amazon a leaf tea is used for liver problems, and the oil of the leaves and unripe fruit is mixed with olive oil and used externally for neuralgia, rheumatism, and arthritis pain. In Jamaica, Haiti, and the W est Indies, the fruit and/or fruit juice is used for fevers, parasites and diarrhea, and as a lactagogue; the bark or leaf is used as an antispasmodic, sedative, and nervine for heart conditions, coughs, grippe, difficult childbirth, asthma, asthenia, hypertension, and parasites. Many bioactive compounds and phytochemicals have been found in graviola, as scientists have been studying its properties since the 1940s. Its many uses in natural medicine have been validated by scientific research. Several studies by different researchers demonstrated that the bark as well as the leaves had hypotensive, antispasm odic, anticonvulsant, vasodilator, smoothmuscle relaxant, and cardiodepressant activities in animals.1,2 Researchers verified graviola leaf's hypotensive properties in rats again in 1991.3 Several studies over the years have demonstrated that leaf, bark, root, stem, and seed extracts of graviola are antibacterial in vitro against numerous pathogens,4–6 and that the bark has antifungal properties.6,7 Graviola seeds dem onstrated active antiparasitic properties in a 1991 study,8 and a leaf extract showed to be active against malaria in two other studies (in 1990 and 1993). 9,10 The leaves, root, and seeds of graviola demonstrated insecticidal properties, with the seeds demonstrating strong insecticidal activity in an early 1940

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not only are effective in killing tumors that have proven resistant to anti-cancer agents. the head pharmacologist in Purdue's research explained how this worked. specific acetogenins in graviola have been reported to be selectively toxic to these types of tumor cells: lung carcinoma cell lines. titled “Recent Advances in Annonaceous Acetogenins.22. . and antiviral properties. pesticidal. graviola leaves and stem showed active cytotoxicity against cancer cells and researchers have been following up on these findings since. In one of their reviews. 22 pancreatic carcinoma cell lines. and fruit seeds. On average. They are potent inhibitors of NA DH : ubiquinone oxidoreductase.11 In a 1997 clinical study. drugs.28 and multi-drug resistant human breast adenocarcinoma. various Annonaceous acetogenins in the plant fam ily have been docum ented with antitumorous.16–19 human breast solid tumor lines." 32 In 1997. novel alkaloids found in graviola fruit exhibited antidepressive effects in animals.13 Much of the cancer research on graviola focus es on a novel set of phytochemicals called Annonaceous acetogenins. They also inhibit the ubiquinone-linked NAD H oxidase that is peculiar to the plasma membranes of cancerous cells.12 In an 1976 plant screening program by the National Cancer Institute.14–21 Many of the acetogenins have demonstrated selective toxicity to tumor cells at very low dosages—as little as 1 part per million. much of which has been funded by The National Cancer Institute and/or the National Institute of Health (NIH). We now understand the primary modes o f action for the acetogenins. even unrelated.31 Mode of action studies in three separate laboratories have recently determined that these acetogenins are superb inhibitors of enzyme processes that are only found in the membranes of cancerous tumor cells.30 Annonaceous acetogenins are only found in the Annonaceae family (to which graviola belongs).g. Purdue U niversity published information with promising news that several of the Annonaceous acetogenins " . has conducted a great deal of the research on the ace togenins .study. Thus far. only about two percent of the cancer cells in any given person might develop this pump— but they are the two percent that can eventually grow and expand to create multi-drug2 . “Recently. Graviola produces these natural compounds in its leaf and stem. . cancer cells that survive chemotherapy can develop resistance to the agent originally used as well as to other. in W est Lafayette. against prostate cancer (PC-3).14."33 In several interviews after this information was publicized.14. we have noticed that. Three separate research groups have isolated these acetogenin com pounds in graviola which have dem onstrated significant antitumorous and anticancerous properties.. and antimicrobial activities.15. A recent report showed that they act directly at the ubiquinone-catalytic site(s) within complex I and in microbial glucose dehydrogenase. although most of acetogenins have high potencies among several solid human tumor cell lines. antiprotozoal. bark.27. Purdue University. and/or international patents on their work around the antitumorous and insecticidal properties and uses of these acetogenins.22–25 Thus far. These types of pumps are capable of pushing anticancer agents out of the cell before they can kill it. e. anthelmintic. As he explains it. As more acetogenins have been isolated and additional cytotoxicity assays have been conducted. One of the ways that cancer cells develop resistance to chemotherapy drugs is by creating an intercellular efflux pump called a P-glycoprotein mediated pump.26. This phenomenon is called multi-drug resistance (MDR).25 liver cancer cell lines.29 human lymphoma cell lines. but also seem to have a special affinity for such resistant cells. which is in an essential enzyme in complex I leading to oxidative phosphorylation in mitochondria. antifeedant. we reported that the Annonaceous acetogenins can selectively inhibit the grow th of cancerous cells and also inhibit the grow th of adriamycin resistant tumor cells. Indiana. Purdue U niversity and/or its staff have filed at least nine U.” they state.25 colon adenocarcinoma cell lines. some of the derivatives w ithin the different structural types and some positional isomers showed remarkable selectivities among certain cell lines. antiparasitic. Four studies were published in 1998 which further specify phytochemicals and acetogenins which are demonstrating the strongest anticancerous. In general. antitumorous. and selective toxicity against various types of cancer cells (without harming healthy cells) publishing eight clinical studies on their findings. 17 prostate adenocarcinoma.S.14.

Purdue researchers reported that 14 different acetogenins tested thus far demonstrate potent AT P blocking properties (including several found only in graviola). patent. annonacin (at a dosage of 10 mg/kg). They inoculated mice with Lewis lung carcinoma cancer cells.34 A tumor cell needs energy to grow and reproduce.9%—slightly better than adriamycin— and without toxicity. and attem pt to synthesize these chemicals into new chemotherapeutic drugs. sedative. annonacin might be used as a lead to develop a potential anticancer agent.6% reduction of tumor mass over the control group—but 50% of the animals had died from toxicity (three of six). antifungal. W hen acetogenins block ATP to the tumor cell over time. several acetogenins found in graviola and other Annona plants have been submitted to the NIH anti-AIDS screening program by Purdue University. As this is a familiar property of Annonaceous acetogenins. With the demise of the world’s tropical rain forests. research w ork is continuing in this area as well. “This suggested that annonacin was less toxic in mice. one third received the chemo-therapy drug adriamycin. is lost. are significantly bioactive and are worthy of fractionation. antiviral. this class of compounds can be expected to continue to grow at an exponential rate in the future. hypotensive. and the tumors were inhibited by 57. vermifuge 3 . pectoral. antitumorous. and one third received the m ain graviola acetogenin. vasodilator. vincristine. anticonvulsant. piscicide. cytotoxic. anticancerous. such work is compelling before the great chemical diversity. At the end of tw o weeks. test.resistant tumors. antidepressant. antispasmodic. In addition. antimicrobial. however. are not adversely affected by ATP inhibitors. and vinblastine) they used as controls. One researcher summarized his work eloquently: “At the time of preparation (August 1998) of this current review. stomachic. On considering the antitumor activity and toxicity. Normal cells seldom develop such a pum p. 34 They also reported that 13 of these 14 acetogenins tested were m ore potent against MDR breast cancer cells than all three of the standard drugs (adriamycin. An interesting in vivo study was published in March of 2002 by researchers in Japan. astringent. insecticide. the cell no longer has enough energy to operate sustaining processes—and it dies. cardiodepressant. Cancer research is ongoing on these important plants and plant chemicals. antineoplastic. The adriamycin group showed a 54. thus. contained within these endangered species. febrifuge. The mice receiving annonacin were all still alive. as several pharmaceutical companies and universities continue to research. they don't require large am ounts of energy to run a pump and.” 34 Perhaps—if enough people believe that the possible cure for cancer or AIDS truly is locked away in a rainforest plant—we will take the steps needed to protect our remaining rainforests from destruction. Documented Properties and Actions: Antibacterial. generally. researchers have reported that NADH dehydrogenase inhibitors can suppress HIV infection. Purdue researchers reported that the acetogenins preferentially killed multi-drug-resistant cancer cells by blocking the transfer of ATP—the chief source of cellular energy—into them. who w ere studying various acetogenins found in several species of plants. over 350 Annonaceous acetogenins have been isolated from 37 species. This led the researchers to summarize. anthelm intic. and a great deal more to run its pump and expel attacking agents. that annonacin only inhibited the normal growth of the lung tumors during this two-week period. antiparasitic. it can no longer run its pump. thereby killing MDR tumors. provided that financial support for such research efforts can be found. By inhibiting energy to the cell . Some of the latest research on acetogenins reported that they were capable of shutting down these intercellular pum ps. One third received nothing. of over 80 Annonaceous species screened. nervine. it did not eradicate the tumors nor stop their growth altogether.” 35 Its important to note. therefore. O ur preliminary efforts show that about 50%. five of the s ix in the untreated control group were still alive and lung tumor sizes were then measured.

It may potentiate antidepressant drugs and interfere with MAOinhibitor drugs. one.). montecristin. gigantetrocinone. cough. liver problems. gallbladder. tranquilizer Brazil Caribbean Curaçao 4 . murihexol. flu. uvariamicin I & IV. however. anthelmintic. annonacin. Graviola has demonstrated emetic properties in one animal study with pigs. vasodilator. corossolone. sedative. gigantetrocin. calmative. muri-catenol. cohibin A thru D. annonacinone. WORLDWIDE ETHNOBOTANICAL USES Country Uses Abscess. annomuricin A thru E. javoricin. muricatetrocin A & B muricatin D. Graviola has demonstrated hypotensive. rolliniastatin 1 & 2. muricatalicin. corepoxylone. annom ontacin.Main Phytochemicals: Annonaceous acetogenins: annocatalin. etc. cis-corossolone. murisolin. rash. intestinal colic. Contraindications: Graviola has demonstrated uterine stim ulant activity in an animal study (rats) and should therefore not be used during pregnancy. murihexocin 3. Supplementing the diet with probiotics and digestive enzym es is advisable if this plant is used for longer than 30 days. chill. nervousness. palpitation. parturition. at a dosage of 300 mg/kg. and cardiodepressant activities in animal studies and is contraindicated for people with low blood pressure. annomutacin. tea. and monomine oxidase activity. norepinephrine. coronin. muracin A thru G. graviola may potentiate antihypertensive and cardiac depressant drugs. solamin. m uricapentocin. fever. donhexocin. epomuricenin A & B. fever. edema. the use of this plant is probably contraindicated in combination with MAO inhibitors and some prescription antidepressants.37 If sedation or sleepiness occurs. dysentery. isoannonacin. sedative. annohexocin. muricin I. however. diabetes. annomuricatin A & B. a reduction in explorative behavior and mild abdominal constrictions was observed. gigantetronenin. Drug Interactions: None have been reported. (multiple iso. nervousness. See contraindications above. annomonicin. Graviola has demonstrated significant in vitro antimicrobial properties. astringent. corossolin. neuralgia. reduce the amount used. rheumatism Antispasmodic. muricatalin. Large single dosages may cause nausea or vomiting. diarrhea. emetic. muricoreacin. cis-annonacin. muricatocin A thru C muricin H. murihexocin A thru C. chest problems.36 As such. bronchitis. analgesic. antispasmodic. skin disease Childbirth. as well as a inhibition of serotonin release in stress-induced rats. montanacin. parasites. goniothalamicin. cis. People taking antihypertensive drugs should check with their doctors before taking graviola and m onitor their blood pressure accordingly (as medications m ay need adjusting). Reduce the usage accordingly if this occurs. xylomaticin Traditional Remed y: The therapeutic dosage is reported to be 5–7 grams daily in capsules or tablets (in 3–4 divided dosages). One study with rats given a stem-bark extract intragastrically (at 10 0 m g/kg) reported an increase in dopamine. Alcohol extracts of graviola leaf showed no toxicity or side effects in mice at 100 mg/kg. annopentocin A thru C. gigantetrocin A & B. Check with your doctor first if you are taking prescription antidepressants or MAO inhibitor drugs prior to taking graviola. saba-delin. indigestion. long-term use of this plant may lead to die-off of friendly bacteria in the digestive tract due to its antimicrobial properties. Chronic. A standard infusion (one c up 2–3 tim es daily) or a 4:1 standard tincture (2–4 ml three times daily) can be substituted if desired. robustocin.

stomachic Antispasmodic. asthma. 1962. A. A. pellagra. et al. 14: 556–61.. et al. fever. hypertension. pectoral. C. “Contribution to the bio logical evaluation of Cuban plants. dys entery. et al. insecticide. et al. 4.” Int. pediculicide. Pharmacog. arthritis. Trop. diuretic. diarrhea. scurvy Anthelmintic. fever. M. E thnopharmacol. lactagogue. ringworm. et al. diarrhea. “Preliminary screening of antibacterial and antitumor activities of Papua New Guinean native medicinal plants. ulcer (stomach). lactagogue. insomnia. childbirth. palpitation. tranquilizer Haiti Jamaica Malaysia Mexico Panama Peru Trinidad West Indies Elsew here References 1. heart. cough.” Rev. vermifuge Antiparas itic.” J.. sedative. 5. Indie. indigestion. 8(6): 64. 10. lactagogue. Pharmacol.” Ann. Pharm. 31(1): 29–35. heart conditions. 1993. et al. antiphlogistic. scurvy. bilious. F. tumors (skin). sedative. hypertension. Cubana Med.” Int. E thnopharmacol.. hypertension. hypertension. “Isoq uin olin e derivatives isolated from the fruit of Annona muricata as 5HT ergic 5-HT1A receptor agonists in rats: unexploited antidepressive (lead) products. spasm. 9. liver. soporific. T. Cubana Med.. dyspepsia.. Bories. kidney. Abraham A. 11. diarrhea. 33(1/2): 21–4. ringworms Asthma. febrifuge. Lopez. Feng. emetic. Pharmacog. et al.Country Uses Asthenia. 31(1): 3–6. K. sedative. 31(4): 255–58. 1997. parasites. diarrhea. et al. 1991. 1993. 1941. liver disorders. pediculicide. et al. boil. Res. J. astringent. fevers. 2. Hasrat. P. antispasm odic. M. D. kidney.” J. grippe. sedative. “In vitro an tim alarial activity of six medicinal plants. insecticide.” Rev.. flu. dermatosis. et al. rheumatism. parasites. fainting. ulcers (internal) Depurative. M. ringworm. heart conditions. "Screening of the flora of Puerto Rico for potential antimalarial bioactives. sore.. 49(11): 1145–49. C. 1979. diabetes. piscicide. M. J. asthenia. 27: 262–73. Trop. “Pharmacological screening of some West Indian medicinal plants. Sundarrao. diarrhea. 1991. 7. catarrh. “Antiparasitic activity of Annona muricata and Annona cherimolia seeds . 1990. diarrhea. Antoun. hypertension.. 12. lactagogue. Carbajal. B iol. 36(1): 81–5. asthma. Appl. nervine. “Parasitological and microbiological evaluation of Mixe Indian medicinal plants (M exico). lice. M. Gbeassor. 3. Misas.” J.. parasites. cicatrizant. pectoral.” Phytother. “Pharmacological screening of plant decoctions c ommonly used in Cuban folk medicine.. cyanogenetic. galactagogue. 6.” Planta Med. I. childbirth. Ned. liqueur. J. J. worms Analgesic. cataplasm. “P lant extracts w ith cytostatic properties growing in Cuba. 5 . dysentery. Tattersfield. styptic Astringent. C. Meyer. malaria. nervine. 8. dysentery. vermifuge Astringent. “The insecticidal properties of certain species of Annona and an Indian strain of Mundulea sericea (Supli). diarrhea. high blood press ure. Pharm. “The alkaloids of Annona muricata. 4(3): 115–17. IV . 31(2): 97–104.” Ing. D. stomach. Heinrich. 57(5): 434–36. Pharmacol.” J. cough. 1992. fever. piscicide. 1940. 1979.

Prod. Nat. “Muricatacin: a simple biologically active acetogenin derivative from the seeds of Annona muricata (Annonac eae)” Tetrahedron Lett.” J. “Effect of Annona muricata and Polyalthia cerasoides on brain neurotransmitters and enzyme monoamine oxidase following cold immobilization stress. Prod. Zeng. mono-tetrahydrofuran acetogenins. P. or prevent any disease. 1995. 29. J. 18. from the leaves of Annona muricata. Nat. “Antibody-catalyzed organic and organometallic transformations and chemical libraries of Annonaceous acetogenins. Rieser.” Bioorg.html Feras. Nat. 1(2): 144–46. et al. Med. 61(5): 576–9. Nat. “Muricoreacin and murihexocin C. et al. 1995. The plant described herein is not intended to diagnose.. from the leaves of Annona muricata. et al. W u. Purdue News September 1997. S. W u. et al. E. Q. M.4-trans and cis)-10Rannonacin-A-ones. 1996. 94(4): 531-35. Oswaldo Cruz 1999. 22. Unpublished data. http://www. C. 25. 2001. W u. 33. W u. 2002. Kim. 1995. et al.. from the leaves of Annona muricata. mitigate. “Structure-activity relationships of diverse Annonaceous acetogenins against multidrug resistant human mamm ary adenocarcinoma (MCF-7/Adr) cells. annomuricin C and muricatocin C.” Planta Med. 1998. “Rec ent advances in Annonaceous acetogenins. et al. Rieser. Prod. et al. 36. M. Nat..” The Skaggs Institute for Chemical Biology S cientific Report 1997–1998. Nat. 19.. J. West Lafayette. F..” J. Prod. 1996. N’gouemo... Ethnopharmacol. E. P. et al. et al.. et al... F. Nat.13. Gleye. 61(4): 432–36. et al. S. et al. et al. 65(4): 470–75. “New bioactive monotetrahydrofuran A nnonaceous acetogenins.” Phytother. Inst. “Effect of the extract of Annona muricata and Petunia nyctaginiflora on Herpes simplex virus.” Mem. 32.. Med. 2002. et al. 15. J. Prod. 31. Betancur-Galvis.” J. “Additional bioactive acetogenins. 61(1): 81–3. “Five new monotetrahydrofuran ring acetogenins from the leaves of Annona muricata. F. 21. Res. C. J.” J. G. Q. E. 37.. J.” J. et al. Padm a. 28. 58(6): 830–36.. “Two new c ytotoxic monotetrahydrofuran Annonaceous acetogenins. L. 59(1): 91–2. 35. 6 . 30. treat. Nicolas...” J. annomuricin E and muricapentoc in. 59(2): 100–8. “Five novel mono-tetrahydrofuran ring acetogenins from the s eeds of Annona muricata. E. 62(3): 504540. Prod. L. 1997.. Anon. 1995. Prod. Zeng. Nat. E.” Nat. 11(3): 243–45. 58(6): 902–8. National Cancer Institute. researc h.purdue. et al.. Prod. Chang. annomuricins A and B. Chem. 58(6): 909–15. 23. Anon. From NAPRA LERT Files. L. 58(9): 1430–37. Keinan. R. Prod Rep. P.” J. 13(4): 275–306. 49(2): 565–71. Phytochem istry 1998. “Annonac eous acetogenins from the leaves of Annona montana.. Jaramillo. “Effects of ethanol extract of Annona muricata on pentylenetetrazol-induced convulsive seizures in mice..” J. M. W ang. et al. “Muricatocins A and B. Nat. et al. C. 34.” J. 1991. “Annonaceous acetogenins: Rec ent progress .” J. “Novel cytotoxic annonaceous acetogenins from Annona m uricata. 16. 20. 1993. Natural Remedies 2001. 27. This information is not intended to be used to diagnose. prescribe or replace proper medical care. Prod..” Fitoterapia 2000. Chem. 26.edu/UNS/newsandphotos. 1997.. Rieser.. et al. 32(9): 1137–40. “Cytotoxicity and antileishmanial activity of Annona mu ricata pericarp. “New cytotoxic monotetrahydrofuran Annonaceous acetogenins from Annona muricata. IN. two new bioactive monotetrahydrofuran Annonaceous acetogenins from the leaves of Annona muricata. L.. 59(11): 1035–42. cure. from the leaves of Annona muricata. 14. et al. Nat Cancer Inst Central Files (1976). “Two new mono-tetrahydrofuran ring acetogenins. annomutacin and (2. “Antitumor and antiviral activity of Colombian medicinal plant extracts. F. 71(2): 183–6. Kim. M. H.” J. 10(3): 561-65. et al. Prod. Nat. 1998. et al. Nat. The information contained herein is intended for education. and informational purposes only. 1996. Prod. 1998. from the leaves of Annona muricata. 24. et al. University of Illinois. F. Padma. 1999. G. “Bioactive single-ring acetogenins from seed extracts of Annona muricata. Liaw.” J.. Purdue University. 1995. “Cis-monotetrahydrofuran acetogenins from the roots of Annona muricata 1. The statements contained herein have not been evaluated by the Food and Drug Administration. 40(13): 2102–6. 64(7): 925–31. 17. C..

Used for the spleen and for fever. Used for ringworm. Tea used by asthma sufferers. Tea used as a sedative and heart tonic. Human A dult Human A dult Human A dult Leaf Curacao A05332 Leaf Dominica Leaf Guatemala Leaf Guam Leaf Guyana Leaf Haiti Hot H2O Ext / Oral Hot H2O Ext / Oral Hot H2O Ext / Oral Hot H2O Ext / Oral Not stated Decoction / Oral Hot H2O Ext / Oral Hot H2O Ext / Oral Human (pregnant) Human A dult Human A dult Human A dult Human A dult Human A dult Human A dult Human Female A01962 M27151 W 01267 ZZ1033 AA1008 T13846 W 01316 Leaf Jamaica 7 . and chest problems. Used for nervousness. diarrhea. Used as an antispasmodic. Used Used Used Used Used Used for liver problems. and asthenia. Decoction drunk for gallbladder trouble. Tea is drunk by women in labor (parturition). and bronchitis. Type Extract Hot H2O Ext / Oral Leaves / External Hot H2O Ext / Oral Infusion /Oral Maceration / External Hot H2O Ext / Oral Maceration / External Decoction / Oral Decoction / External Decoction / Oral Hot H2O Ext / Oral Method Human Adult Human Adult Human Human Human Human Human Human A dult Adult A dult A dult A dult A dult Ref # T05032 K27823 ZZ1024 L15585 ZZ1002 ZZ1072 ZZ1072 ZZ1099 K20471 Leaf Cook Islands Used to treat skin rashes.Documented Ethnomedical Information for Graviola (Annona muricata) Part Used / Where Leaf Barbados Leaf Borneo Leaf Brazil Documented Use Used as a sedative. and nervine. externally for neuralgia. for dysentery. and skin infections. rheumatism. sedative. Used for grippe. intestinal colic. Beverage prepared as a lactagogue. edema. as an anthelmintic and antirheumatic. coughs. rheumatism and arthritis pain. cough. Infusion used as an antispasmodic. cough. for spasms. Used to treat indigestion. for abscesses. skin diseases.

coughs. internal ulcers. Considered emetic and astringent. hypertension and parasites. and parasites. coughs. Claimed to be a tranquillizer. and parasites. Used for malaria. fevers. grippe. hypertension. Used for high blood pressure and diarrhea. asthma. Tea used as a sedative and heart tonic. Used for hypertension. Crushed seeds and seed oil used as an insecticide. hypertension. grippe. coughs. asthma. hypertension. Used for indigestion and catarrh. Decoction used to ease delivery. diarrhea. asthenia. Used to kill parasites. difficult childbirth. diabetes. asthma. dysentery. sedative. liver disorders. Used to treat heart palpitations. liver maladies and malaria. Used as an astringent and a styptic. Used as a sedative and antispasmodic. and grippe. for skin parasites and lice. sores. Used to treat catarrh. sedative. Used to lower high blood pressure and as a galactagogue.Part Used / Where Leaf Jamaica Documented Use Used as an antispasmodic. and nervine for heart conditions. Type Extract Not Stated Method Human A dult Ref # ZZ1020 Leaf Madagascar Leaf Malaysia Infusion / Oral Decoction / Oral Leaves / External Decoction / Oral Decoction / Oral Decoction / Oral Cataplasm / External Human A dult Human A dult Human A dult Human A dult Human A dult Human A dult Human A dult L15693 K26834 J13478 L04137 ZZ1045 ZZ1093 ZZ1093 Leaf Peru Leaf Surinam Leaf Togo Leaf Trinidad Leaf West Indies Infusion / Oral Decoction / Oral Hot H2O Ext / Oral Hot H2O Ext / Oral Hot H2O Ext / Oral Hot H2O Ext / Oral Not stated Decoction / Oral Maceration/ External Hot H2O Ext / Oral Decoction / Oral Human A dult Human A dult Human A dult Human (pregnant) Human A dult Human Adult Human A dult Human A dult Human A dult Human A dult Human A dult J14527 M23556 T05032 T00701 T00701 ZZ1021 ZZ1099 ZZ1027 ZZ1093 ZZ1033 AA1008 Seed B razil Seed Peru Bark Guyana Bark Haiti Bark Jamaica Used as an antispasmodic. and nervine for heart conditions. Fresh leaves crushed with salt are used in a cataplasm to “ripen” malignant tumors. asthenia. Used for heart conditions. Used for difficult childbirth. Hot H2O Ext / Oral Human A dult ZZ1020 8 . difficult childbirth. worms and diarrhea.

Used to treat diabetes. and antidiabetic. Used for hypertension and parasites. Type Extract Decoction / Oral Hot H2O Ext / Oral Fruit / Oral Fruit / Oral Method Human A dult Human A dult Human A dult Human A dult Ref # ZZ1045 ZZ1021 AA1008 ZZ1020 Fruit Wes t Indies Rootbark B razil Root Peru Used for fevers. Considered calmative. Used as a sedative and antispasmodic. Used as a sedative and antispasmodic. Used for fevers. parasites. Used for fevers. diarrhea and as a lactogogue. antispasmodic. parasites. parasites. Fruit / Oral Decoction / Oral Hot H2O Ext / Oral Human A dult Human A dult Human A dult ZZ1021 ZZ1099 ZZ1045 9 . diarrhea and as a lactogogue.Part Used / Where Bark Peru Bark West Indies Fruit Haiti Fruit Jamaica Documented Use Used to treat diabetes. diarrhea and as a lactogogue.

033 ml/liter 100.0 mg/kg Active Active Active Active Active Active Active Active A03360 A03360 Heart BP fell by more than 30%.05 Level.0 ml/animal 0. Minimum toxic dose 1. Reduction in explorative behavior and abdominal constrictions observed. Hind Quarter (isolated) vs. strychnine-induced convulsions. Uterus (unspec. Ref # K29500 K29500 Leaf + Stem Jamaica Leaf Not stated Toxicity Assessment (quantitative) Cytotoxic / Antiproliferative Activity H2O Ext Fraction: Annonacin IP Mouse IP Mouse Various 10 mg/kg A03360 AA1032 Leaf + Stem Jamaica Leaf + Stem Jamaica Bark Not stated Leaf Cuba Leaf + Stem Jamaica Leaf Gabon Uterine Stimulant Effect Hypertensive Activity Cardiac Depressant Activity Hypotensive Activity Vasodilator Activity Anticonvulsant Activity ETOH(95%) Ext H2O Ext ETOH(95%) Ext H2O Ext H2O Ext H2O Ext ETOH(95%) Ext ETOH(95%) Ext Oral Rat Oral Rat IV Dog IV Dog Rabbit IV Rat IP Rat IP Mouse 0.1 ml/kg 0.033 ml/liter 0.cond). metrazole-induced convulsions and vs.1 ml/kg Not stated 1.0 mg/kg 300.Documented Biological Activities for Extracts of Graviola (Annona muricata) IN VIVO RESEARCH Plant Part / Origin Leaf Gabon Leaf Gabon Activity Tested For Toxic Effect (general) Toxic Effect (general) Type Extract ETOH(95%) Ext ETOH(95%) Ext Test Model IP Mouse IP Mouse Dosage 100. vs.0 ml/animal.0 mg/kg Results Inactive Active Notes / Organism Tested No toxicity noted. vs.cond).9% without toxicity Uterus (unspec.0 gm/kg Inactive M18488 10 . pentylenetetrazolinduced seizures. writhing test. Results significant at P < 0. A04104 M29843 A03360 K29500 Leaf Nigeria Anticonvulsant Activity ETOH(70%) Ext IP Mouse Dose Variable Inactive T06510 Leaf Brazil Analgesic Activity ETOH-H2O (1:1) Ext Intragastric Mouse 1. Active Inhibited the growth of Lewis lung carcinoma tumors by 57.033 ml/liter 0.

0 gm/kg 3.0 mg/kg Active vs. cold stress-induced ulcers.033 ml/liter 0.Plant Part / Origin Leaf Brazil Leaf + Stem Jamaica Leaf + Stem Jamaica Leaf Cuba Activity Tested For Analgesic Activity Smooth Muscle Relaxant Activity Spasmogenic Activity Inotropic Effect Positive Type Extract ETOH-H2O (1:1) Ext ETOH(95%) Ext H2O Ext ETOH(95%) Ext H2O Ext Hot H2O Ext Test Model Intragastric Mouse Rabbit Rabbit Guinea Pig Guinea Pig Guinea Pig Dosage 1.0 mg/kg 100.0 mg/kg 100.3 ml/liter 2.0 mcg/ml J10986 Seed Surinam MEOH Ext J10986 Stembark India Stembark India Stembark India Stembark India ETOH(100%)Ext ETOH(100%)Ext ETOH(100%)Ext ETOH(100%)Ext 100. Inhibited the binding of 3h-rauwolscine to serotonin receptors.0 mg/kg Active Weak Activity L19052 J19242 Leaf Surinam Serotonin (5-ht) Receptor Binding Activity Serotonin (5-HT) Receptor Binding Activity Serotonin (5-HT) Receptor Binding Activity Dopamine Increase Norepinephrine Level Increase Monoamine Oxidase Activity Increase Serotonin (5-ht) Release Inhibition CHCL3 Ext Calf Hippocampus Calf Calf Calf Hippocampus Rat Intragastric Rat Intragastric Rat Intragastric Rat Intragastric 100. Inhibited the binding of 3hrauwolscine to serotonin receptors.0 mg/kg 100.032 ml/liter Results Inactive Active Active Active Active Inactive Notes / Organism Tested vs.0 mg/kg 100.033 ml/liter 0.0 mcg/ml Weak Activity Active Active Active J10986 Fruit Surinam Juice CHCL3 Ext 100.2 ml/liter 0. cold immobilization stress-induced increase in lipid peroxidation.0 mcg/ml 100. Duodenum Ileum Atrium Ref # M18488 A03360 A03360 M29843 Stembark India Antioxidant Activity ETOH(95%)Ext Rat Intragastric 100.0 mg/kg Active Active Active Active L19052 L19052 L19052 L19052 11 . Inhibited the binding of 3h-rauwolscine to serotonin receptors. Brain Brain Brain Brain J10426 Stembark India Stembark India 5-hydroxyindole-3-acetic Acid Inhibition Antiulcer Activity ETOH(100%)Ext ETOH(100%)Ext Rat Intragastric Rat Gastric Intubation 100. Brain Statistical data in report indicating significant results vs.0 mcg/ml 100. tail flick test.

9 mcg/ml IC50=0. Murine leukemia L1210.67 mcg/ml ED50<20.Documented Biological Activities for Extracts of Graviola (Annona muricata) IN VITRO RESEARCH Plant Part / Origin Leaf Malaysia Activity Tested For Epstein-barr Virus Early Antigen Induction Cytotoxic Activity Cytotoxic Activity Cytotoxic Activity Cytotoxic Activity Cytotoxic Activity Cytotoxic Activity Cytotoxic Activity Cytotoxic Activity Cytotoxic Activity Cytotoxic Activity Type Extract Ether Ext Test Model Cell Culture Dosage 1.) Cancer: CA-9KB. human breast carcinoma MCF-7.0 mcg/ml ED50=1.0 mcg/ml Not stated Not stated Not stated Active Active Active Active Active Active Active Active Active Active K27823 X00001 X00001 L12082 H24563 H19306 X00001 AA1009 AA1017 AA1020 Seed France Cytotoxic Activity Fractions: Acetogenins Not stated Not stated Active AA1031 12 .15 Six human tumor cell lines including prostate adenocarcinoma (PC-3) and pancreatic carcinoma (PACA-2) cell lines.0 mcg/ml ED50<20 mcg/ml ED50<20 mcg/ml IC50=2.Epstein-barr (Assay designed to test for tumor promoting activity.0 mcg/ml Results Inactive Notes / Organism Tested Virus .15 Human hepatoma Hep G(2) and 2. Ref # J13478 Leaf Borneo Leaf Costa Rica Leaf USA-FL Leaf Colombia Leaf Indonesia Leaf Indonesia Stem Costa Rica Leaf Taiwan Seed China Seed Korea ETOH(95%) Ext ETOH(95%) Ext ETOH(95%) Ext ETOH(100%) Ext ETOH(95%)Ext Not stated ETOH(95%)Ext ETOH(95%)Ext Fractions: Acetogenins Fractions: Acetogenins Cell Culture Cell Culture Cell Culture Cell Culture Cell Culture Cell Culture Cell Culture Cell Culture Cell Culture BST 20.05 level) Cancer: CA-9KB Cancer: CA-9KB Cells-MDBK Cancer: CA-Mammary-MCF-7 Cancer: CA-A498 Cancer: CA-9KB Human hepatoma Hep G 2. (Results significant at p < 0. human breast adenocarcinoma MDA-MB231.2.2.

human H8. Human solid tumor cell lines.) Neurospora crassa AA1030 AA1021 Acetogenins France Cytotoxic Activity Fractions: Acetogenin analogs H2O Ext ETOH Ext Ketonic Ext Fractions: Acetogenins Cell Culture Not stated Active AA1015 Leaf Cuba Cytostatic Activity Agar plate Not stated Active AA1013 Acetogenins USA Cytostatic Activity Not stated Not stated Active Adriamycin resistant human mammary adenocarcinoma (MCF-7/Adr) cells. P03. adriamycin resistant tumor cells.5 mcg/ml Not stated Active Active Human hepatoma 2 Murine P388 leukemia. Cancer: U-937 Ref # H22688 Stembark USA Cytotoxic Activity Fractions: Acetogenins Cell Culture Not stated Active AA1025 Bark USA Leaf + Twig USA Bark Venezuela Pericarp Colombia Cytotoxic Activity Cytotoxic Activity Cytotoxic Activity Cytotoxic Activity Fraction: Gigantetronenin Not Stated Fraction: Xylomaticin Hexane Ext Ethyl acetate Ext MEOH Ext MTT Fractions: Acetogenins Cell Culture Cell Culture Cell Culture Cell Culture Not stated Not stated Not stated Not stated Active Active Active Active AA1026 AA1023 AA1024 AA1029 Leaf Colombia Acetogenins USA Cytotoxic Activity Cytotoxic Activity Cell Culture Cell Culture CC50=49.H125 cancer cell lines. L1210 leukemia cells (Predicts antitumor activity. HT-29 (colon adenocarcinoma) Human tumor cell lines. Human tumor cell lines A549 (lung carcinoma). Human tumor cell lines. MCF7 (breast carcinoma). AA1015 13 .Plant Part / Origin Leaf USA Activity Tested For Cytotoxic Activity Type Extract Fractions: Muricoreacin Murihexocin C Test Model Cell Culture Dosage Not stated Results Active Notes / Organism Tested Six human tumor cell lines including prostate adenocarcinoma (PC-3) and pancreatic carcinoma (PACA-2) cell lines. M17/adr cancer cell lines. nonadriamycin resistant tumor cells.

Herpes simplex 1 Neurospora crassa Ref # AA1011 AA1021 H16272 Stem Puerto Rico Cytotoxic / Anti-HIV Activity H2O Soluble Fraction IC50<2.17 mcg/ml Results Active Inactive Active Notes / Organism Tested Demonstrated antitumor activity. Virus .0 mcg/ml Active L09586 Stem Puerto Rico Colombia Stembark India Leaf Cuba Antiviral Activity Antiviral Activity Antiviral Activity Antifungal Activity H2O Soluble Fraction MTT ETOH(95%) Ext Acetone Ext ETOH(95%) Ext H2O Ext Hot H2O Ext Agar Plate Cell Culture Cell Culture Agar Plate Not stated CC50 & EC50 = 0.0 mg/ml 50% Inactive Active Active Inactive L09586 AA1030 J19169 T08589 Leaf Guatemala Antifungal Activity Broth Culture 1. Assay system is intended to predict for antitumor activity. Non-cancerous GI epithelial cell line (I18). vs.HIV Virus .Plant Part / Origin Seed China Acetogenins USA Leaf Indonesia Activity Tested For Antitumor Activity Antiproliferative Activity Anticrustacean Activity Type Extract CHC13 Ext Fractions: Acetogenins ETOH(95%) Ext Test Model Cell Culture Cell Culture Artemia salina larvae Cell Culture Dosage Not stated Not stated LC50=0.HSV-2 Virus.50 mcg/ml 1.0 mg/plate Weak Activity Hepatocytes (Measured by leakage of LDH and ASAT.0 ml Inactive Epidermophyton floccosum Microsporum canis Microsporum gypseum Trichophyton mentagrophytes Trichophyton rubrum Neurospora crassa M27151 Stem Cuba Antifungal Activity Acetone Ext ETOH(95%) Ext H2O Ext Decoction Agar Plate 50% Inactive T08589 Leaf Dominican Republic Antihepatotoxic Activity Cell Culture 1. Results indicate it has an antiproliferative effect rather than a cytotoxic effect on HIV-infected cells. Reduced the leakage of ASAT) K23019 14 . CEM-SS Cells.

dessetae A. histolytica N.0 mg/plate Results Inactive Notes / Organism Tested Hepatocytes (Monitored by production of malonaldehyde. salina Plasmodium falciparum W-2 Plasmodium falciparum D-6 Plasmodium falciparum Plasmodium falciparum D-6 & W-2. promastigotes E.Plant Part / Origin Leaf Dominican Republic Leaf Dominican Republic Stembark France Pericarp Colombia Activity Tested For Antioxidant Effect Type Extract H2O Ext Test Model Cell Culture Dosage 1.0 mcg/ml Weak Activity Inactive Active Active K16971 K16971 M23556 K27823 Leaf Cuba Antibacterial Activity H2O Ext Agar Plate Not stated Active K09159 Stembark Papua-New Guinea Stem Cuba Antibacterial Activity Antibacterial Activity MEOH Ext Acetone Ext Agar Plate Agar Plate 1 mg/disc Not stated Active Active L03211 K09159 15 . Leishmania trypansoma Leishmania braziliensis L.0 mcg/ml IC50 > 63 mcg/ml IC50=39.0 mg/liter Inactive K23019 Antiparasitic Activity Antiparasitic Activity MEOH Ext Hexane Ext Ethyl Acetate Ext MEOH Ext MEOH Ext In vitro In vitro Not stated Not stated Active Active AA1032 AA1029 Seed France Antiparasitic Activity In vitro Not stated Active M28527 Leaf Puerto Rico Leaf Puerto Rico Leaf Togo Leaf Borneo Antimalarial Activity Antimalarial Activity Antimalarial Activity Antimalarial Activity ETOH(95%) Ext ETOH(95%) Ext ETOH(95%) Ext ETOH(95%) Ext RBC RBC RBC RBC IC50=20. (Results significant at P < 0.01 Level) Escherichia coli Pseudomonas aeruginosa Shigella flexneri Staphylococcus aureus Escherichia coli Escherichia coli Salmonella B Salmonella newport Salmonella typhosa Shigella flexneri Shigella flexneri 3A Ref # K23019 Radical Scavenging Effect H2O Ext Not stated 250. panamensis L.) Measured by decoloration of diphenylpicryl hydroxyl radical solution.9 mcg/ml 20. brasiliensis M.

0 mg/disc Not stated L03211 L03211 K09159 L03211 K09159 16 .0 mg/disc 1.Plant Part / Origin Leaf Cuba Activity Tested For Antibacterial Activity Type Extract Acetone Ext Test Model Agar Plate Dosage Not stated Results Active Notes / Organism Tested Escherichia coli Pseudomonas aeruginosa Salmonella B Salmonella newport Salmonella typhosa Serratia marcescens Shigella flexneri Shigella flexneri 3a Staphylococcus albus Staphylococcus aureus Escherichia coli Pseudomonas aeruginosa Salmonella newport Salmonella typhosa Salmonella B Shigella flexneri Bacillus subtilis Staphylococcus albus Klebsiella pneumoniae Pseudomonas aeruginosa Staphylococcus aureus Escherichia coli Staphylococcus aureus Sarcina lutea Escherichia coli Escherichia coli Pseudomonas aeruginosa Salmonella B Salmonella newport Salmonella typhosa Sarcina lutea Serratia marcescens Shigella flexneri Shigella flexneri 3a Staphylococcus albus Staphylococcus aureus Ref # K09159 Stem Cuba Antibacterial Activity H2O Ext Agar Plate Not stated Active K09159 Stembark Papua-New Guinea Antibacterial Activity ETOH(95%) Ext Agar Plate 2-3 mcg/plate Active Active Inactive Inactive Weak Activity Weak Activity Inactive Inactive Inactive K15021 Leaf Papua-New Guinea Stembark Papua-New Guinea Leaf Cuba Leaf Papua-New Guinea Leaf Cuba Antibacterial Activity Antibacterial Activity Antibacterial Activity Antibacterial Activity Antibacterial Activity ETOAC Ext MEOH Ext ETOAC Ext Acetone Ext ETOAC Ext ETOH(95%) Ext Agar Plate Agar Plate Agar Plate Agar Plate Agar Plate 1.0 mg/disc Not stated 1.

Plant Part / Origin Leaf Trinidad Activity Tested For Antibacterial Activity Type Extract ETOAC Ext Test Model Agar Plate Dosage 1000 mcg/ml Results Inactive Notes / Organism Tested Escherichia coli Pseudomonas aeruginosa Salmonella typhimurium Staphylococcus aureus Staphylococcus epidermidis Streptococcus faecalis Pseudomonas aeruginosa Sarcina lutea Serratia marcescens Staphylococcus albus Staphylococcus aureus Salmonella B Salmonella newport Salmonella typhosa Sarcina lutea Serratia marcescens Shigella flexneri 3a Staphylococcus albus Staphylococcus aureus Staphylococcus aureus Streptococcus faecalis Escherichia coli Salmonella typhimurium Staphylococcus epidermidis Sarcina lutea Serratia marcescens Shigella flexneri 3A Staphylococcus albus Staphylococcus aureus Ref # L13922 Stem Cuba Antibacterial Activity Acetone Ext Agar Plate Not stated Inactive K09159 Leaf Cuba Antibacterial Activity H2O Ext Agar Plate Not stated Inactive K09159 Leaf Trinidad Antibacterial Activity Pet Ether Ext Agar Plate 1000 mcg/ml Equiv. Equiv. Inactive Inactive Inactive Inactive L13922 Stem Cuba Antibacterial Activity H2O Ext Agar Plate Not stated K09159 17 .

59 ppm LD50 = 20.03 gm/ml 5.0 ppm LD50 = 1.62 ppm 0.0 ppm LD50 = 0. L12432 L15585 L15585 L15585 AA1028 AA1012 M19731 W00220 AA1018 AA1019 AA1018 AA1010 18 .0% Not stated Not stated Not stated 18 mcg/ml Inactive Inactive Active Active Active Active Inactive Weak Activity Active Active Active Equiv. decemlineata M.26 ppm LD90 < 20 ppm LD90 < 20 ppm LD50 = 11. persicae Blattella germanica (L.97 ppm LD50 = 1. decemlineata Dopaminergic nerve cells and GABAergic nerve cells.86 ppm LD50 = 49. Ref # K09159 Leaf Puerto Rico Stem Brazil Dried Stembark Brazil Leaf Brazil Leaf Brazil Brazil Leaf + Stem India Leaf Not Stated Spain USA Spain Root bark Taiwan Antimycobacterial Activity Molluscicidal Activity Molluscicidal Activity Molluscicidal Activity Molluscicidal Activity Molluscicidal Activity Larvicidal Activity Insecticide Activity Insecticide Activity Insecticide Activity Antifeedant Activity Dopaminergic modulation ETOH(95%) Ext ETOH(100%) Ext ETOH(100%) Ext ETOH(100%) Ext Not stated Not stated H2O Ext ETOH(95%) Ext Fraction: Squamocin Fraction: Acetogenins Fraction: Annonacin Alkaloid Ext Agar Plate Not stated Adult snail Egg masses Adult Snail Egg Masses Adult Snail Egg Masses Adult Snail Egg Masses Not stated Not stated Agar plate In vitro Agar plate Cell culture Not stated 100.) L.Plant Part / Origin Stem Cuba Activity Tested For Antibacterial Activity Type Extract ETOH(95%) Ext Test Model Agar Plate Dosage Not stated Results Inactive Notes / Organism Tested Escherichia coli Pseudomonas aeruginosa Salmonella B Salmonella newport Salmonella typhosa Sarcina lutea Serratia marcescens Shigella flexneri Staphylococcus albus Staphylococcus aureus Mycobacterium tuberculosis Biomphalaria glabrata Biomphalaria glabrata Biomphalaria glabrata Biomphalaria glabrata Biomphalaria glabrata Biomphalaria glabrata Culex quinquefasciatus Macrosiphoniella sanborni L.

0003% 00.0032% 01.0021% Not stated 00.00035% 00.00035% 00.0004% 00.00521% Ref # AA1009 H17799 H07609 H07609 AA1009 H21843 H16272 L07801 H16272 H16273 H24563 H19306 H19306 H17568 L07801 K20560 K10338 H07236 H19768 H16272 L07801 H16274 H22999 H22999 Annomuricin B Annomuricin C Annomuricin E Annomuricin-D-one. cis: Annomuricin-D-one.00566% 00.0021% 00.Presence of Compounds in Graviola (Annona muricata) Compound Annocatalin Annohexocin Annomonicin Annomontacin Annomontacin.0003% 00.00142% 00.02674% Not stated 00.00906% 00.06818% 00.00603% Not stated 00.0% 00.05411% 00.0004% 00.000235 00. trans Annomutacin Annonacin Annonacin A Misc Lactone 19 . cis Annomuricatin B Annomuricin A Chemical Type Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Plant Part Leaf Leaf Seed Seed Seed Seed Leaf Pericarp Leaf Leaf Leaf Leaf Leaf Leaf Pericarp Seed Seed Seed Root Leaf Pericarp Leaf Seed Seed Plant Origin Taiwan Not stated Guyana Guyana Taiwan China Indonesia Colombia Indonesia Indonesia Indonesia Indonesia Indonesia Indonesia Colombia Brazil USA Guyana Guinea Indonesia Colombia Indonesia China China Quantity Not stated Not stated 00.

2% 01. iso: Annonacin-10-one.00017% 00. iso: 2-4-cis: Annonacin.Compound Annonacin B M esitoate Annonacin. iso: 2-4-trans: Chemical Type Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Plant Part Not stated Seed Seed Leaf Leaf Seed Seed Seed Seed Seed Seed Leaf Leaf Seed Seed Seed Seed Fruit Leaf Leaf Leaf Root Bark Leaf Plant Origin China Dominican Republic USA Indonesia Indonesia China China USA Dominican Republic USA China Indonesia Indonesia Guyana Guyana Brazil Guyana Surinam Indones ia (cult) Indones ia (cult) Indones ia (cult) Guyana Guyana Guyana Quantity Not stated 00.0005% 00.00035% Not stated Not stated Not stated Ref # H20484 H18307 K10338 H16274 H16274 AA1011 AA1011 K10338 H18307 K10338 H15501 H17568 H17568 H07609 H07609 K20560 H07236 J14527 H19306 H19306 H19306 T02076 T04073 T04073 Annonacin.00017% 00.00277% Not stated Not stated Not stated Not stated 00. cis: Annonacin.000909% 00. iso: Annonacin. cis-2-4: 10(r): Annonacin-A-one.00136% 00. cis: Annonacin-10-one. trans-2-4: 10(r): Annonacinone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Annonaine Annopentocin A Annopentocin B Annopentocin C Anomuricine Isoquinoline A lkaloid Misc Lactone Misc Lactone Misc Lactone Isoquinoline A lkaloid 20 .00109% 00. 2. iso: 10-one.07% 00.00113% Not stated 00.00697% Not stated 00.01811% 00. iso: neo: Annonacin-A-one.0004% 00.4-trans Annonacin-10-one Annonacin-10-one.

0003% 00.00062% Not stated Not stated Not stated 00.01% Not stated Ref # T02076 T04073 T04073 J10986 A04099 W 02289 J10986 A04095 T02076 T04073 T02076 T04073 T04073 H26434 H19768 H26434 H19768 H26434 H26434 H12235 T02076 T04073 T04073 H28460 H07236 K20560 H28040 Anonaine Anonol Isoquinoline A lkaloid Alkanol C5 or More Asimilobine Atherospermine Atherosperminine Isoquinoline A lkaloid Isoquinoline A lkaloid Isoquinoline A lkaloid Coclaurine.Compound Anomurine Chemical Type Isoquinoline A lkaloid Plant Part Root Bark Leaf Fruit Leaf Leaf Fruit Stembark Root Bark Root Bark Leaf Seed Root Seed Root Seed Seed Seed Root Bark Leaf Root Seed Seed Seed Plant Origin Guyana Guyana Guyana Surinam Dominican Republic W est Indies Surinam Philippines Bark Bark Guyana Guyana Guyana Brazil Guinea Brazil Guinea Brazil Brazil Brazil Guyana Guyana Guyana Guinea Guyana Brazil Taiwan Quantity Not stated Not stated Not stated Not stated Not stated Not stated Not stated Not stated Not stated Not stated Not stated Not stated Not stated Not stated 00.00116% Not stated Not stated Not stated Not stated 00. (+): Coreximine. (-): Misc Lactone Misc Lactone Misc Lactone Isoquinoline A lkaloid Isoquinoline A lkaloid Coronin Coross olin Misc Lactone Misc Lactone 21 .00290% 01.(+): Isoquinoline A lkaloid Cohibin A Misc Lactone Cohibin B Misc Lactone Cohibin C Cohibin D Corepoxylone Coreximine.

00221% 00.00278% Not stated 00.0005% Ref # H07236 K20560 H14312 H28040 AA1009 H22999 Coross olone.4-trans Gigantetronenin Goniothalamicin Benzenoid Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Goniothalamicin.00042% Not stated Not stated 00.00072% Not stated Not stated H14312 H19768 H14312 H19768 A06190 K10338 H12985 H12985 AA1011 AA1011 H16273 H07609 K10338 H16272 H18307 K20560 H18307 H18307 W 02289 A04099 Epomuricenin B Misc Lactone Gentisic A cid Gigantetrocin Gigantetrocin A Gigantetrocin B Gigantetrocinone.00278% Not stated Not stated 00.Compound Corossolone Chemical Type Misc Lactone Plant Part Seed Seed Seed Seed Leaf Seed Plant Origin Guyana Brazil Brazil Taiwan Taiwan China Quantity 00.00059% Not stated 00. 2.00136% Not stated Not stated Not stated 00. cis: Javoricin KCL Misc Lactone Misc Lactone Inorganic .00127% 00.00568% Not stated 00. cis Donhexocin Misc Lactone Misc Lactone Epomuricenin A Misc Lactone Seed Root Seed Root Leaf Seed Seed Seed Seed Seed Leaf Seed Seed Leaf Seed Seed Seed Seed Leaf Leaf 22 Brazil Guinea Brazil Guinea Trinidad USA Dominican Republic Dominican Republic China China Indonesia Guyana USA Indonesia Dominican Republic Brazil Dominican Republic Dominican Republic W est Indies Dominican Republic 00.00181% 00.02% 00.4-cis Gigantetrocinone. 2.00232% 01.01660% 00.

00233% Not stated Not stated Not stated Not stated Not stated Not stated Not stated 00.Compound Lignoceric Acid Linoleic A cid Chemical Type Lipid Lipid Plant Part Leaf Leaf Leaf Seed Seed Root Seed Seed Seed Seed Seed Seed Seed Leaf Leaf Leaf Seed Seed Leaf Seed Seed Leaf Seed Seed Leaf 23 Plant Origin Dominican Republic W est Indies Dominican Republic China Guyana Guinea Taiwan Taiwan Taiwan Taiwan Taiwan Taiwan Taiwan Indonesia China China China Dominican Republic Indonesia Taiwan Dominican Republic Indonesia Taiwan China Indonesia Quantity Not stated Not stated Not stated Not stated 00.02490% 00.00028% Not stated Not stated Not stated 00.00045% Not stated Not stated 00.00045% Not stated Not stated 00.00085% 00.00045% Ref # A04099 W 02289 A04099 AA1017 H07609 H19211 H28040 H28040 H28040 H28040 H28040 H28040 H28040 H24563 AA1027 AA1027 AA1011 H12985 H16272 H28040 H12985 H16272 H28040 H21114 H16274 Longifolicin Montanacin Montecristin Muracin A Muracin B Muracin C Muracin D Muracin E Muracin F Muracin G Muricapentocin Muricatalicin Muricatalin Muricatenol Muricatetrocin A Not stated Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Muricatetrocin B Misc Lactone Muricatin D Muricatocin A Misc Lactone Misc Lactone .

00035% Not stated 00.0093% Not stated Not stated Not stated Not stated 00. cis Reticulatacin.00311% 00.00060% 00.Compound Muricatocin B Muricatocin C Muricin H Muricin I Muricine Chemical Type Misc Lactone Misc Lactone Misc Lactone Misc Lactone Alkaloid-misc Plant Part Leaf Leaf Seed Seed Bark Plant Origin Indonesia Indonesia Taiwan Taiwan Not stated Quantity 00.00216% 00.00015% 00. cis: Reticuline Not stated Misc Lactone Misc Lactone Isoquinoline A lkaloid 24 .00083% Not stated N-fatty acyl tryptamines Oleic Acid Lipid Lipid Otivarin Panatellin.00930% 00. epoxy: Murisolin Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Leaf Leaf Leaf Leaf Seed Stembark Seed Seed Seed Seed Seed Leaf Leaf Not stated Root Root Stembark Indonesia USA USA Indonesia China India French Guiana China Brazil Guyana China Dominican Republic W est Indies Italy Guinea Guinea Philippines 00.00038% Not stated Not stated 00.0004% Not stated Not stated Not stated Not stated Ref # H16274 H16273 AA1009 AA1009 A04104 A05062 A04104 A05062 H22688 H17719 H17719 H22688 H22999 H12242 H06211 H21114 H14312 H07236 AA1011 A04099 W 02289 AA1022 H21880 H21880 A04095 Muricinine Alkaloid-misc Bark Not stated Not stated Muricoreacin Murihexocin 3 Murihexocin A Murihexocin C Murihexol Murin A.

n-para-coumaroyl: Uvariamicin I.00043% 00.0005% Not stated H14312 H12242 K20560 K20560 H07234 H21880 H17568 H21880 H21880 AA1009 Solamin.00116% 00.Compound Reticuline. cis Xylomaticin Misc Lactone Isoquinoline A lkaloid Misc Lactone Misc Lactone Misc Lactone OTHER PHYTOCHEMICAL SCREENING: Alkaloids Absent Alkaloids Present Leaf + Stem Bark + Leaf + Seed Leaf Entire Plant Entire Plant Entire Plant Entire Plant Entire Plant T05306 L16047 A04099 T06830 T06830 T06830 T06830 T06830 25 Hydrocyanic Acid Absent Leucoanthocyanins Present Quinones Absent Saponins Absent . cis: Tyramine.00036% Not stated Not stated 00. cis: Uv ariamicin IV.00083% 00.00285% Not stated Not stated 00.00116% Ref # T02076 T04073 T04073 H26304 H21114 K20560 K20560 H25221 Robustocin Rolin B.00216% Not stated 00.00005% 00. epoxy: Rolliniastatin 1 Rolliniastatin 2 Sabadelin Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Solamin Misc Lactone Seed Stembark Seed Root Seed Root Leaf Root Root Seed Brazil India Brazil Guinea French Guiana Guinea Indonesia Guinea Guinea Taiwan 00. (+) Chemical Type Isoquinoline A lkaloid Plant Part Root Bark Leaf Seed Seed Seed Seed Seed Plant Origin Guyana Guyana Guyana Brazil China Brazil Brazil Guinea Quantity Not stated Not stated Not stated 00.

Graviola (Annona muricata) Please purchase the Graviola Technical Data Report to obtain these cited references.Literature Cited . (Pages 26-38) AA1008 AA1009 AA1010 AA1011 AA1012 AA1013 AA1014 AA1015 AA1017 AA1018 AA1019 AA1020 AA1021 26 .

Fitoterapia 2000 Apr. gigantetrocin-B (7). Its fractionation led to the isolation of three acetogenins--annonacin.. Liaw. The acetogenins of Annonaceae are known by their potent cytotoxic activity. et al.15 cell line. and corossolone. R. and corossolone (12). 2.4-trans-form for the first time (no cis-form). panamensis promastigotes.4-cis-Gigantetrocinone (2) and 2. annonacinone. et al. eth yl acetate and methanol extracts of Annona muricata pericarp were tested in vitro against Leishmania braziliensis and L..2.4-trans-gigantetrocinone (3) have been isolated as their acetates by preparative TLC. C. 39 . Hexane. annomontacin. J Nat Prod 2001 Jul. we have prepared a series of bis-tetrahydrofuranic acetogenins with different functional groups along the alkyl chain. specific inh ibitors of mitochondrial comp lex I. they are promising cand idates as a new future generation of antitumoral drugs to fight against the current chemio-therapic resistant tumors. The main target enzyme of these compounds is complex I (NADH :ubiquinone oxidoreductase) of the mitochondrial respiratory chain. Jaramillo..71(2):183-6 Cytotoxicity and antileishmanial activity of Annona muricata pericarp. and xyloma tic in. The CHCl3 fraction of the seeds showed strong antitumor activities. murisolin. longifolicin (10). Compound 5 showed a high selectivity toward the Hep 2. annomontacin (8).2. These acetogenins showed significantly selective in vitro cytotoxicities toward the human hepatoma cell lines Hep G(2) and 2. together with four known ones. annonacin. muricin H (1). The structures of all new isolates were elucidated and characterized by spectral and chemical methods.4-trans-Isoannonacin-10-one (4) and 2. Li. C. annonacin A and annomuricin A. D.. F. Gallardo. annonacin. Seven new annonaceous acetogenins. Y. and cis-annomontacin (3).65(4):470-5 New cytotoxic monotetrahydrofuran annonaceous acetogenins from Annona muricata.15. Hep G(2) and 2. M. In an attempt to characterize the relevant structural factor of the acetogenins that determines the inhibitory potency against this enzyme.. cis-corossolone (4) and annocatalin (5). solamin. a mixture of muricatetrocin A (8) and muricatetrocin B (9). along with five known acetogenins.43(25):4793-800 Sem isynthesis of antitumoral acetogenin s: SAR of functionalized alkyl-chain bis-tetrahydrofuranic acetogenins. and against cell line U-937. J Asian Nat Prod Res 2001.15.4-trans-isoannonacin (5) have been isolated as only 2.3(4):267-76 Ann onaceo us acetogen ins of the seeds from Ann ona mu ricata. gigantetrocin-A (6). gigantetronenin (9) and a mixture of N-fatty a cyl tryptamines have been isolated (10). Muricatenol (1) is a new C37 non-THF ring acetogenin with four hydroxyls and one isolated double bond in the long aliphatic chain. The structures of all isolates were elucidated and characterized by spectral and chemical methods.64(7):925-31 Novel cytotoxic annonaceous acetogenins from Annona muricata.Clinical Abstrasts J Nat Prod 2002 Apr. These new acetogenins exhibited significant activity in in vitro cytotoxic assays against two human hepatoma cell lines. T. as well as five known compounds. J Med Chem 2000 Dec 14. Also four known acetogenins. 2. muricins A-G (1-7). muricin I (2). Their structures have been established on the basis of spectral analyses. C. Additionally. Three new monotetrahydrofuran annonaceous acetogenins. a key enzymatic complex of energy metabolism. were isolated from the leaves of this species. annonacinone. et al. In fact. The ethyl acetate extract was more active than the other extracts and even of Glucantime used as reference substance. were isolated from the seeds of Annona muricata. Chang. et al. were isolated from the seeds of Annona muricata. corossolin (11). two new monotetrahydrofuran annonaceous acetogenins.2. et al.

et al. Kim. Betancur-Galvis.122(3):171-83 Specific interactions of monotetrahydrofuranic Annonaceous acetogenins as inhibitors of mitochondrial comp lex I... On recent studies.000 times the potency of adriamycin. K orea. H. mono-tetrahydrofuran aceto-genins.000 times cytotoxic as adriamycin in the pancreatic cell line (PaCa-2). known for their cytotoxicity were used as pos-itive controls. A. ACG are currently being tested on standard antitumor trials although little is known about the structure ac tivity relationship at the molecular level. Chem Biol Interact 1999 Nov 1. Annonaceous acetogenins (ACG) are a wide group of cytotoxic compounds isolated from plants of the Annonaceae family. et al Extracts of nine species of plants traditionally used in Colombia for the treatment of a variety of diseases were tested in vitro for their potential antitumor (cytotoxicity) and antiherpetic activity. The mixture of 2 and 3 is ov er 10.(Annonaceae) resulted in the isolation of two new Annonaceous acetogenins. cherimolia and Rollinia membranacea. These species are good candidates for further activity-monitored fractionation to identify active principles. et al. 40 . T he 50% cytotoxic c oncentration (CC 50) and the 50% inhibitory concentration of the viral effect (EC50) for each extract were calculated by linear re-gression analysis. on Hep-2 cells presented a CC50 value at 72 hr of 49.49(2):565-71 Muricoreacin and murihexocin C.4)-cis-and trans-isoannonacins: cytotoxic monotetrahydrofuran annonaceous acetogenins from the seeds of Annona cherimolia. from the leaves of Annona muricata. cis -Annonacin (1) and the mixture of (2.22(5):524-8 cis-Annonacin and (2. main gate of the energy production in the cell.4)-cis-and trans-isoannonacins (2 and 3). W oo. Tormo. Neither of the other extracts examined showed a significant cytotoxicity. Phytochemistry 1998 Sep.Me Arch Pharm Res 1999 Oct. Catholic University of Taegu-Hyosung. Likewise. Compounds 1 and 2 showed significant cytotoxicities among six human tumor cell lines with selectivities to the prostate adenocarinoma (PC-3) and pancreatic carcinoma (PACA-2) cell lines. muricoreacin (1) and murihexocin C (2). R. Extracts from Annona muricata. Their structures were elucidated based on spectrosc opic and chemical methods . three known mono-tetrahydrofuran annonaceous acetogenins. MTT (Tetrazolium blue) and Neutral Red colorimetric assays were used to evaluate the re-duction of viability of cell cultures in presence and absence of the extracts. G. Inst Oswaldo Cruz 1999 Jul-Aug.. 1 showed potent cytotoxicities in the brine shrimp lethality test (BST) and among six human solid tumor cell lines with notable selectivity for the pancreatic cell line (PaCa-2) at about 1.94(4):531-5 Antitumor and antiviral activity of Colombian medicinal plant extracts. MTT was also used to evaluate the effects of the extracts on the lytic activity of herpes simplex virus type 2 (HSV-2). showed some antiherpetic activity with acceptable therapeutic indexes (the ratio of CC50 to EC50). Some of them are promising candidates to be a future new generation of antitumor drugs due to the ability to inhibit the NAD H:ubiquinone oxidoreductase of the res piratory chain (mitochondrial complex I). L. The aqueous extract from Bet a vu lgaris. S. K yongsan. All of the compounds are about 10 to 100 times as cytotoxic as adriamycin in the prostate cell line (PC-3). have been isolated from the seeds of Annona cherimolia by the use of the brine shrimp lethality test (BST) for bioactivity directed fractionation. Bioactivity-directed fractionation of the leaves of Annona muricata L. the ethanol extract from Callisia grasilis and the methanol extract Annona sp. Methanolic extract from Annona sp. the relevance of several parts of the molecule for the inhibitory potency has been evaluated. College of Pharmacy.6x10(3)mg/ml. J. et al.. acyclovir and heparin were used as positive controls of antiherpetic activity. Department of Pharmacy. M.

Oberlies. Compounds 1 and 2 are monotetrahydrofuran ring acetogenins bearing tw o flanking hydroxyl groups. especially with regard to MDR tumors. thus.. with selectivities to the pancreatic carcinoma (P ACA-2) and colon adenoc arcinoma (HT-29) cell lines. and development of these compounds since December 1995. they exhibit their potent bioactivities through depletion of ATP levels via inhibiting complex I of mitochondria and inhibiting the NADH oxidase of plasma membranes of tumor cells. and single-THF ring(s). Biologically. Fourteen structurally diverse Annonaceous acetogenins. Both 1 and 2 showed significant cytotoxicities against six types of human tumors. Bioassays of the pure compounds. and in a panel of human solid tum or cell lines for cytotoxicity. arianacin (4). Chemically. Ethnopharmacol 1998 May. biology. et al.61(4):432-6 Two new m ono-tetrahydrofuran ring acetogenins. A spacing of 13 carbons between the flanking hydroxyl of the THF ring system and the gamma-unsaturated lactone seem s to be optimum with a spacing of 11 and 9 carbons being significantly less active. Q.5. and javoricin (5). vincristine. Thus. and 2 has a 1.62(3):504-40 Annonaceous acetogenins: recent progress. Three of these (1-3) are among the first cis mono-tetrahydrofuran ring acetogenins to be reported. Padma. The min imum inhibitory concentration of ethanolic extract of A.9-triol moiety. G. The Annonaceous acetogenins are promising new antitumor and pesticidal agents that are found only in the plant family Annonaceae. cis-annonac in-10-one (2). Alali. cis -gon iothalamic in (3).2-diol.. representing the three main classes of bis-adjacent. et al. Several single-THF ring compounds were also quite potent with gigantetrocin A (11) being the most potent com pound tes ted. Bioactivity-directed fractionation of the seeds of Annona muricata L. We have looked at the ability of extract(s) to inhibit the cytopathic effect of HSV-1 on vero cells as indicative of anti-HSV-1 potential. bis-nonadjacent. J Nat Prod 1998 Apr. were tested for their ability to inhibit the growth of adriamycin resistant human mamm ary adenocarcinoma (MCF-7/Adr) cells. for the inhibition of crown gall tumors.. Bioactivity-directed fractionation of the leaf extract of An nona muricata L. and vinblastine and is. M . J. Among a series of bis-adjacent THF ring acetogenins. J Nat Prod 1996 Feb. et al. (Annonaceae) resulted in the isolation of five new compounds : cis-annonac in (1).S. N. NMR analyses of published model synthetic compounds. Compound 1 has an erythro 1. annomuricin E and muricapentocin. The acetogenins may. Kim. from the leaves of Annona mu ricata.61(1):81-3 Effect of the extract of Annona muricata and Petunia nyctaginiflora on Herpes simplex virus. et al. muricata and aqueous extract of P. 41 .40(13):2102-6 Structure-activity relationships of diverse Annonaceous acetogenins against multidrug resistant human mammary adenocarcinoma (MCF-7/Adr) cells. (Annonaceae) has resulted in the isolation of two new Annonaceous acetogenins. multidrug resistant (MDR). This review presents the progress made in the chemistry. J Med Chem 1997 Jun 20.59(2):100-8 Five novel mono-tetrahydrofuran ring acetogenins from the seeds of Annona muricata.H. Annona muricata (Annonac eae) and Petunia nyctaginiflora (Solana-ceae) were screened for their activity against Herpes simplex virus-1 (HSV-1) and clinical isolate (obtained from the human keratitis lesion). and prepared Mosher ester derivatives permitted the determinations of absolute stereochemistries. prepared cyclized formal acetals. however.. they thwart ATP-driven resistance mechanisms. have chem otherapeutic potential. in the brine shrimp test. Rieser.J Nat Prod 1999 Mar. This cell line is resistant to treatment with adriamycin. each has three additional hydroxyl groups. those with the stereochemistry of threo-trans-threo-trans-erythro (from C-15 to C-24) were the most potent with as much as 250 times the potency of adriamyc in.. thus. et al. F. annomuricine (1) and muricapentoc in (2). they are derivatives of long-chain fatty acids. P. nyctaginiflora was found to be 1 mg/ml.

The C-10/C-11 and C-10/C-12 acetonides (1c. and pancreatic (PACA-2) cell lines with potencies equal to or exceeding those of Adriamycin. annomutacin [1]. 42 . J Nat Prod 1995 Sep. not described previously from this plant. nmr. W u. and 2 and 3 were selectively cytotoxic to lung carcinoma cells (A-549). and C(3). gigantetronenin. colon (HT-29). annomuricin C and muricatocin C.. three novel monotetrahydrofuran Annonac eous acetogenins. Compounds 1-3 are the first acetogenins reported bearing a mono-tetrahydrofuran (THF) ring with one flanking hydroxyl. irrespective of their various structural types. E. and the absolute configurations were determined by Mosher ester methodology. 2c) suggested relative stereochemistry and significantly enhanced the cytotoxicities against the A-549 human lung and the M CF-7 hum an beas t solid tumor cell lines. N-p-c oumaroyl tyramine. H. two hydroxyl groups are at the C-10/C-11 and C-10/C-12 positions in 1 and 2. and single tetrahydrofuran (THF) ring compounds and their respective ketolactone rearrangement products. Zeng. Compound 1 and the mixture of compounds 2 and 3 showed selective cytotoxicities against the human A-549 lung tumor cell line. were determined by Mosher ester methodology. The cell inhibition activities of several Annonaceous acetogenins. W u. The results demonstrate a dose-dependent inhibition of cancerous cell growth. Compound 1 was selectively cytotoxic to pancreatic carcinoma cells (PAC A-2). These results show that the Annon-aceous acetogenins are an extremely potent class of compounds. Bioactivity-directed fractionation of the leav es of Annona m uricata res ulted in the isolation of annopentocins A (1). and uv spectral and chemical methods.and trans-annomuricin-D-ones (4. PO3.evaluated relative potencies. A known bioactive amide. et al.10R-annonacin-A-one [2].. Compounds 1 and 2 each possess five hydroxyl groups. J Nat Prod 1996 Nov.000 times the potency of adriamycin.4-trans and cis)-10R-annonacin-A-ones. that is one carbon away from the THF ring.59(11):1035-42 Five new mon otetrahydrofuran ring acetogenins from the leaves of Annona mu ricata. namely. respectively. et al. All of the acetogenins. (2.58(9):1430-7 Additional bioactive acetogenins. while exhibiting only minimal toxicity to 'normal' non-cancerous cells. the mixture of 4 and 5 was selectively cytotoxic for the lung (A-549). was also found. on the lactone side. from the leaves of Annona mu ricata. Compound 1 was selectively cytotoxic to colon adenocarcinoma cells (HT-29) in which it was 10.96(1):55-62 Tumor cell growth inhibition by several Annonaceous acetogenins in an in vitro disk diffusion assay. One known monotetrahydrofuran acetogenin. were tested in an in vitro disk diffusion as sa y ag ain st three murine (P388. bis-non-adjacent.. on the hydrocarbon side. et al.4-trans). and cis. In a continuation of our research on bioactive components from the leaves of Annona muricata. and their inhibition of cell growth can be selective for canc erous cells and also effective for drug resistant cancer cells. E. and another hydroxyl. annomutacin and (2. from the leaves of Annona mu ricata. annomuricin C [1] and muricatocin C [2]. inhibit the growth of adriamycin resistant tumor cells and non-resistant tumor cells at the same levels of potency. J Nat Prod 1995 Jun. F. while non-cancerous cell growth is not inhibite d by the same dosages.58(6):909-15 New bioactive monotetrahydrofuran Annonaceous acetogenins. covering the three major structural classes of bis-adjacent. 5). Cancer Lett 1995 Sep 4. ir. F.. The leaves of Annona muricata have yielded two additional monotetrahydrofuran Annonaceous acetogenins. L. et al. B (2). was also found. N. and M17/Adr) and two human (H8 and H125) cancerous cell lines as well as a non-cancerous immortalized rat GI epithelia l cell line (I18). Compounds 4 and 5 were obtained in a mixture and are new mono-THF ring acetogenins bearing two flanking hydroxyls and an erythro-diol located between the THF and the ketolactone rings. and (2. Oberlies.4-cis)-10R-annonacin-A-one [3]. have been identified. Their structures were deduced by ms. except for positions C-10 and C-11 or C-12. The absolute configurations of 1 and 2.

4-cis)-isoannonacin. from the in hib ition of oxygen consumption by rat liver mitochondria. muricatocins A [1] and B [2]. Three known monotetra-hydrofuran acetogenins. and human breast carcinoma MCF7 cell lines and compared with adriamycin. antimalarial. annonacin A. The sources.58(6):902-8 Muricatocins A and B.monotetrahydrofuranyl acetogenin from Annona mon tana] Joss ang. (2. Landolt. Strategies for structural elucidation are reviewed. antimicrobial. two new bioactive monotetrahydrofuran Annonaceous acetogenins from the leaves of Annona muricata.derived fatty acid deriva tiv es that possess tetrahydrofuran rings and a methylated gamma-lactone (sometimes rearranged to a methyl ketolactone) with various hydroxyl.54(4):967-71 [Annomonysvin: a new cytotoxic gamma-lactone. The acetogenins had earlier been determined to be pesticidal. The cytotoxicities in vitro of annomontacin [I]. W u. antifeedant.. with two hydroxyl groups at the C -10 and C-12 positions.. et al. cytotoxic. A new group of natural compounds. J Nat Prod 1991 Jul-Aug. J. They exhibit a broad range of potent biological activities (cytotoxicity. at NADH. J. F. several available acetogenins have been tested. J Nat Prod 1990 Mar-Apr. The C-10. and annonacin were measured against murine leukemia L1210. chemistry. Chem Biol Interact 1995 Oct 20. and pesticidal). a novel monotetrayhydrofuran fatty acid gamma-lactone (acetogenin) isolated from the seeds of Amnona montana.L. Data obtained. Each compound posses ses five hydroxyl groups. annonacinone [2]. the A nnonaceous acetogenins. 2c) suggested relative stereochemistry and significantly enhanced cytotoxicity against the A-549 human lung tumor cell line. i. and structural revisions and refinements are suggested for some of the previously published compounds. and/or ketoxyl groups along the hydrocarbon chain.. The absolute configurations of 1 and 2 (exce pt for p ositions C-10 and C-12) were determined by Mosher ester methodology. antimalarial. published to date. at the subcellular level. isolation. acetoxyl. were also found. et. 43 .98(1):1-13 Determination of structure-activity relationships of Annonaceous acetogenins by inhibition of oxygen uptake in rat liver mitochondria. antitumor. was determined by spectral analysis. have recently been determin ed to inhibit ATP production at a similar site of action and higher levels of p ote nc y as rotenone. A. In order to determine structural activity relationships (SARs) among these compounds.e. C-12 acetonides (1c.J Nat Prod 1995 Jun. human breast adenocarcinoma MDA-MB 231. antimicrobial. complex I of the mitochondrial electron-transport chain. Rupprecht.53(2):237-78 Annonaceous acetogenins: a review. and biological actions of these compounds. The leaves of Annona m uricata have yielded the novel monotetra-hydrofuran Annonaceous acetogenins. E. et al. and in vivo active as potentially new antitumor agents. and (2.. are tabulated and discussed. biogenesis. The IC50 value of rotenone was 17 nM/mg protein. demons trated that all of the twenty acetogenins tested are active with IC50 values in the range of 15-800 nM/mg protein. anti-parasitic..4-trans)-isoannonacin. The Annonac eous acetogenins are a s eries of apparently polyketide.ubiquinone oxido-reductase. et al. al. The structure of annomontac in [I]. K. immunosuppressant.

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