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Novel drugs from marine microorganisms

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 Critical Reviews in Microbiology, 2011; 37(3): 245–249
© 2011 Informa Healthcare USA, Inc.
ISSN 1040-841X print/ISSN 1549-7828 online
DOI: 10.3109/1040841X.2011.576234

Review Article

Novel drugs from marine microorganisms

Faraza Javed1, M. Imran Qadir1, Khalid Hussain Janbaz2, and Muhammad Ali3
Critical Reviews in Microbiology Downloaded from informahealthcare.com by IBI Circulation - Ashley Publications Ltd on 07/12/11

College of Pharmacy, Government College University, Faisalabad, Pakistan, 2Department of Pharmacy, Bahauddin
1

Zakariya University, Multan, Pakistan, and 3Institute of Biotechnology, Bahauddin Zakariya University, Multan, Pakistan

Abstract
Marine microorganisms have expected mounting consideration on the basis of bioactive metabolites and propose an
exclusive prospect to both enhance the amount of aquatic natural foodstuffs in clinical trials as well as speed up their
progress. This review focuses particularly on those molecules, originated from marine microorganisms, presently in
the medical pipeline that have been recognized or highly expected to be identified based on growing incidental
evidence. Particularly karlotoxin class compounds, isolated from dinoflagellate Karlodinium veneficum, offer chances
to create new molecules for control of cancer and high serum cholesterol levels.
Keywords:  Marine microorganisms, Bioactives, Aquatic foodstuff, Biofilms
For personal use only.

Introduction
Drug development is a very important component of
microbiology (Qadir and Malik, 2010; Qadir and Malik,
2011). While oceans cover more than 70% of Earth’s
surface, aquatic derived microbial natural foodstuffs
have been chiefly unexplored. The aquatic environment
is a home for various exclusive microorganisms, which
generate biologically active complexes called bioactives.
Plants and their extracts have been utilized for the man-
agement of various human diseases for millennia, and
their use has also been recorded in most ancient archae-
ological resource (Penseyan et al., 2010; Newman et al.,
2000). In contrast, the discovery of microbes as manufac-
turer of therapeutically agents began in the 20th century.
However, despite this short history, almost 10% of all
presently known biologically active natural foodstuffs/
products are of microbial origin. These include majority
of antibiotics, visibly indicating the potential of microbes
as a rising and promising source for the creation of bio-
logically active products (Newman et al., 2003).
Definitely, by the 20th century, microbial resultant
bioactives had become the basis of recent pharmaceuti-
cals. Over the past decade, marine microbes have been
acknowledged as a significant and untapped source for
novel bioactive complexes and compounds (Hentschel
et  al., 2007). However, it is significant to carry out a vital
research on marine environment in order to authorize the
persistent identification of distinctive microorganisms. An
emerging source of the new bioactive may result from many
modern studies of microbial diversity in marine environ-
ment, chiefly those microbes which couple with marine
animals and plants. Several researches have confirmed that
“living surfaces” symbolize an environment which is rich
in the epibiotic microorganisms that synthesize bioactive.
Nevertheless, the enormous biotechnological prospective
of the marine epibiotic microorganisms has remained
unexplored. There is still limited knowledge of the physi-
ological requirements of most marine microorganisms.
Nevertheless a greater understanding of their conditions
for growth will offer new insights into the complex world
of marine microbiology (Guo et al., 2002). Consequently, a
greater investment in the development of marine biotech-
nology will produce novel compounds that may contrib-
ute significantly toward drug development over the next
decade. We have discussed the importance of exploring
new sources potentially rich in bioactives, and highlight the
significance of considering the chemical ecology of marine
microorganism-host associations for the targeted isola-
tion of bioactive producing microorganisms. Inspection
of medical proposition by the source has confirmed that

Address for Correspondence:  M. Imran Qadir, College of Pharmacy, Government College University, Faisalabad, Pakistan.
E-mail: mrimranqadir@hotmail.com

(Received 05 March 2011; revised 25 March 2011; accepted 25 March 2011)

245
 246  Faraza Javed et al.
natural foodstuffs and correlated drugs are used to treat
87% of all sorts of human diseases, including as anticancer,
antibacterial, anti-parasitic, anticoagulant, and immuno-
suppressant agents, and so on. Up to 2000, there was no
entry of any innate or natural foodstuffs or related drugs
for 7 drug categories: antihistamine, antianginal, anesthet-
ics, chelator, anxiolytic and diuretic, antidote, and hyp-
notics (Oftedal et al., 2010; Cabrita et al., 2010). In case of
antibacterial agents, natural products and other foodstuff
have made major contributions as either direct treatment
or model for synthetic modifications. More than 79% of the
drugs that became commercially available in the United
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States or were officially approved worldwide from 1982 to
2002 can be traced from a natural product origin based on
species studied. Most of new compounds reported from the
marine microorganisms have been found from those spe-
cies that might be isolated from both sea and land. Although
all these facultative species of marine are undoubtedly a
good source of new metabolites, their degree of adaptation
and ecological roles to the marine environment is mostly
unknown (Jayakumar et al., 2010; Kobayashi et al., 1997).
Drug Discovery From Marine Microorganisms
1. Marine bacteria
Majorly marine bacteria are discussed according to the
sea water requirement or specifically sodium for their
For personal use only.
growth. When marine bacteria which are separated from
the surface of invertebrates and marine algae, undergoes
the process of screening, we recognized that grand pro-
portion of bacteria generates antimicrobial metabolites.
In 1996, the 1st antibiotic was produced by the marine
bacteria (Cuevas and Francesch, 2009; Ocio et al., 2009).
Furthermore, bacteria which are found in biofilms (which
is formed on the surface of the marine microorganisms)
hold a greater percentage of bacteria that produce antibi-
otics than any other marine environment. Some marine
epiphytic bacteria, joined with nutrient rich surfaces of
invertebrates and marine algae have exposed the fact that
they produce antibacterial secondary metabolites that
actually slow down the resolution of potential competi-
tors. Recent researches have revealed that a large number
of surfaces associated-bacteria produce different anti-
biotics. Now days, novel cyclic decapeptide antibiotic,
loloatin B, which inhibits the growth of VRE (vancomycin
resistant Enterococcus), and MRSA (methicillin resistant
Staphylococcus aureus) is obtained from Bacillus spe-
cies isolated from marine worm in Papua New Guinea.
Another new antibiotic thiomarinol is produced by a
marine bacterium Alteromonas rava. Many antibiotics
have been reported from Bacillus including loloatins,
sesbanimides, and agrochelin from Agro bacterium pela-
giomicins and pyrones from Pseudomonas (Mikami et al.,
1985; Cuevas et al., 2000).
2. Marine sponges
Over the past 35 years, the secondary metabolites of
many marine organisms have been studied widely.
 Critical Reviews in Microbiology
During the 1970s, a small number of chemists began to
reveal and isolate novel compounds from the marine
source. Researches of drug discovery from marine micro-
organisms have accelerated and now interdisciplinary
researches are also involved like biochemistry, ecology,
biology, pharmacology, and organic chemistry (Newman
and Eribulin, 2007). Due to the extensive biodiversity of
organisms that has found in widespread oceans and seas
that cover more than 70% of the world, marine micro-
organisms have gained much attention. From marine
microorganisms, novel and structurally distinctive sec-
ondary metabolites have isolated and recognized. As a
result of this struggle, many compounds following new
chemical model have been developed and launched in
2004, while most of other contestants are in clinical trials
(Demydchuk et al., 2008).
Sponge specific microbial societies in the marine
sponges, including novel lineages and candidate phyla
proved as a milestone by the discovery of phylogenetic
complex. Microorganisms are more reachable than those
of sea water in various ways due to which unique research
prospects have been opened up. Most of marine sponges
act as microbial fermentors which provide thrilling new
avenues in marine microbiology and biotechnology
(Harvey et al., 2007; Hoshi and Endo, 2000).
3. Marine fungi
Nowadays, number of compounds derived from marine
fungi are in clinical pipeline, among which Sorbicillacton
A is also included. This compound is extracted from a
fungus associated with marine sponge and provides
an advance stage of development for medical treat-
ment. Many marine fungi produce antioxidant com-
pounds such as Acremonin from Acremonium species,
Xanthenes derivative from Wardomyees anomalus and
4,5,6-Trihydroxy Methyphthalide from Epioeeum species.
These antioxidants keep away from oxidative damages
linked with diseases such as dementia, atherosclerosis
and cancer. They may also be helpful as therapeutics or
food additives (Peng et al., 2010). Marine Actinomycetes
particularly Salinospora group within the family
Micromonosporaceae, that belongs to the antibiotic
producing bacteria, are very promising. These microor-
ganisms are found to be a powerful source as anticancer
agents that basically target the proteosomes function.
Nereus Pharmaceutical has validated their industrial
potential to develop these anticancer agents. Recently
some research teams have successfully identified and
isolated agricultural fungicides, shrimp feed supple-
ment, biofertilizers and cholesterol-reducing drugs from
marine microbes (Hill, 2004).
All these researches are limited to those marine
microbes which are easily culturable. The genome
sequencing makes it possible to visualize potential meta-
bolic and biochemical capabilities of even unculturable
marine microbes. One of the future research trends must
be focused on bio-active substances derived from non-
culturable marine microorganisms (Baldwin, 1992).

Most of prokaryotes from the marine sponges have
been broadly characterized while sponge-inhabiting
fungi were being explored. Adolf et  al. (2009) charac-
terized and isolated a fungal strain from a wild sponge
Scalarispongia scalaris (Cacospongia scalaris) origi-
nated from shallow waters, from the island of Lesvos,
Northern Aegean Sea, Greece. The fungus was anno-
tated as Alternaria sp. on the base of results of the phe-
notypical and molecular analysis. It exhibited almost
same growth kinetics both in the absence and presence
of NaCl in different kinds of growth media. The fungal
antimicrobial activity was studied in vitro, antagonistic
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assays against both yeast (Saccharomyces cerevisiae)
and bacterial (Escherichia coli, Pseudomonas species,
Bacillus subtilis) strains. For all the above strains, a fact
that renders this fungus a potential source of antimicro-
bial substances, clear inhibition zones were observed
(Wang, 2008).
4. Marine nematodes
A hierarchical diversity index–taxonomic distinctness
index showed that the Bohai Bay and other coastal sites
might be disturbed by gas and oil production and many
other anthropogenic influences. In other words we can
say that, an anthropogenic disturbance was affecting
these components of the benthos in these locations.
And most of shore sampling sites in the middle of the
For personal use only.
Bohai Sea were clean, clear and unpolluted due to the
compounds secreted from marine organisms especially
nematodes (Peng et al., 2007).
5. Marine Cyanobacteria
It was suggested that marine Cyanobacteria had ability
for induction of cell death in acute myeloid leukemia
cells. About half of 41 strains of screened cynobacte-
ria, exhibited cancerous cell death (Bachvaroff et  al.,
2008).
Various strains of Cyanobacteria contain apoptosis
activity against acute myeloid leukemia cells but provide
no harm to non malignant cells, e.g., hepatocytes and
cardiomyoblasts. One of its strain (M44) is specifically
promising because of its activity which counteracts the
safety effects of the LEDGF/p75 which is overexpressed
in acute myeloid leukemia and performs its action by
combining with the daunorubicin, an anthracycline
anticancer drug, in AML cells which protect cardiomyo-
blasts from the poisonous effect of the anthracyclines.
By exploring the modern researches, it may be conclude
that culturable benthic Cyanobacteria from the temper-
ate marine environments provides a promising underex-
ploited way for novel drugs against leukemia (Place and
Deeds, 2004; Peng et al., 2010).
6. Marine algae
Marine algae make a series of metabolites halogenated
in nature with prospective mark-able value. Structures
of such compounds undergo acyclic entity with linear
chains to complex and difficult polycyclic molecules. For
© 2011 Informa Healthcare USA, Inc.
Novel drugs from marine microorganisms  247
a few decades, their pharmaceutical and medical appli-
ances have been explored (Van Wagoner et  al., 2008).
During the last years, many unique compounds were
discovered, researches continued but most of the algal
species were inadequately screened. The main empha-
size is on the ecological role of halogenated metabolites
of marine algae that has someway been ignored. New
researches in this field will give new approaches to com-
prehend biodiversity as well as many helpful and unique
insights into marine ecosystem dynamics. But the chal-
lenging target for the coming years will be to understand
the interaction between halogenated compound produc-
tion and environmental changes including global climate
changes (Sheng et al., 2010). Recent researches have been
focused on macro algae than on phytoplankton for the
production of halogenated metabolites. Yet, phytoplank-
ton might be a promising stuff as it is the foundation of
the marine food chains with fast adaptation to environ-
mental changes, which undoubtedly has consequences
on secondary metabolism (Place et al., 2009; Berg et al.,
2002).
7. Chitins
Chitin and chitosan are biodegradeable, non-toxic,
and biocompatible natural marine biopolymers. The
attractive feature of these biomaterials is that, they can
easily converted into other forms like gels, membranes,
sponges, microparticles, scaffold, nanofibers, and nano-
particles for various biomedical applications like cancer
targeting drug, gene transfer, wound dressing and tissue
engineering. Recently two- or three-dimensional chitin-
ous scaffolds from marine sponges origin have been dis-
covered and researches on their applications are under
process (Ablan et al., 2006; Luo et al., 2008).
8. Marine functional food
There is a wide range of chemical and biological diver-
sity in the marine environment. A number of materi-
als, derived from the marine environment, have been
used as food and food ingredients; the most common
are alginate, marine polysaccharides: carrageenan
and agar. Most recent bioactive substances like marine
oils and glucosamine have been added to food list for
additional health benefits. Nowadays functional foods
consisting of omega-3 fats are extensively consumed
with a variety of new products worldwide each year
(Fantini et  al., 2002; Fantini and Barrantes, 2009). In
additional the omega-3 fats and glucosamine a variety
of other marine materials are being developed as func-
tional food ingredients (Agargun et  al., 2004; Pandey
and Sassetti, 2008).
Marine Drugs In Clinical Pipeline
Many marine bacterial derived and other compounds
are in clinical pipeline (Scheuer, 1996). Molecules in
clinical or preclinical evaluation and prototype natu-
ral products are: Solblidotin, Tasidotin, Dolastatin,
 248  Faraza Javed et al.
Salinosporamide A, Bryostatin, Plinabulin, Phenylahistin,
Halimide, Trabectedin, Cyanosafracin B, Eribulin mesy-
late, Halichondrin B, Tetronamycin, Nigericin, K41A,
Manzamine A, Ircinal A, Karlotoxin. These compounds
have variety in their use (Penseyan et al., 2010; Newman
et  al., 2000). Some others are Aplidine, Bryostatin,
Didemin B, Ecteinascidin 743, Kahalaide F, Mycaperoxide
B as anticancer, Cyclodidemniserinol trisulphate,
Lamellarin A 20 sulphate against HIV, Dithiocyanates
against nematode infection, Contignasterol for asthma
and Conotoxins for pain (Rinehart et  al., 1998; Yamada
et  al., 2000; Rinehart, 2000; Zewail-Foote et  al., 1999;
Critical Reviews in Microbiology Downloaded from informahealthcare.com by IBI Circulation - Ashley Publications Ltd on 07/12/11
Kijjojoa and Sawangwong, 2004).
Trabectedin is produced by symbiotic bacteria and
recently approved for cancer treatment. Zalypsis and
Trabectedin have prominently comparable ring system to
the saframycin which is produced by bacteria. Moreover,
Trabectedin could be produced semi synthetically based
upon the Pseudomonas fluorescens and Cyanosafracin B
(Rinehart, 2000; Zewail-Foote et  al., 1999). A variant of
the sponge is Eribulin mesylate which is basically isolated
polyether Halichondrin B (Alchorn, 2007). Polyether pro-
duced by bacteria such as Nigericin, Tetronamycin, and K
41A have almost related structures to the compounds of
Halichondrin family proposing the chances of microbial
creation (Alchorn, 2007; Simons and Ehehalt, 2002).
For personal use only.
Conclusion
Marine microbiology began in the late 19th century and
emerged as a very fascinating and interesting field of
biology. Ocean voyages and missions held during l855
to 1890 had put down an establishment for consequent
microbiological studies of the oceans. The roles of
marine microorganisms in different fields like produc-
tivity, ecology, bio film, and food chain production were
discovered between 1975 to 1980. After 1980, biotechnol-
ogy appeared as an emerging field which gave direction
to the study of marine microbes for biotechnological
aspects like microbial drugs and genomic identification.
These aspects gained much importance during l990–2005
and finally resulted in the production of novel products
and new techniques. Now the invention of scanning
electron microscope and fluorescent probes is very use-
ful to understand the behavior and actions of bacteria.
Researches are going on by using the advanced tools. A
future progress of the marine microbiology is based on
new instruments and methodologies yet to be built-up.
Declaration of interest
No competing financial interests exist.
References
Ablan S., Rawat S., Viard M, Wang J, Puri A, Blumenthal R. (2006).
The role of cholesterol and sphingolipids in chemokine receptor
function and HIV-1 envelope glycoprotein-mediated fusion. Virol
J, 3, 104.
 Critical Reviews in Microbiology
Adolf JE, Bachvaroff TR, Place AR. (2009). Environmental modulation
of karlotoxin levels in strains of the cosmopolitan dinoflagellate,
Karlodinium veneficum (Dinophyceae). J Phycol, 45, 176–192.
Agargun M, Dulger H, Inci R, Kara H, Ozer O, Sekeroglu M, Besiroglu
L. (2004). Serum lipid concentrations in obsessive-compulsive
disorder patients with and without panic attacks. Can J Psychiatry,
49, 776–778.
Alchorn A. (2007). Lipid rafts observed in cell membranes. Sci Tech
Rev, 9.
Bachvaroff TR, Adolf JE, Squier AH, Harvey HR, Place AR. (2008).
Characterization and quantification of karlotoxins by liquid
chromatography-mass spectrometry. Harmful Algae, 7, 473–484.
Baldwin JE. (1992). Biosynthesis of manzamines, Tetrahedron Lett, 33,
2059–2062.
Berg J, Tymoczko J, Stryer L. (2002). The Biosynthesis of Membrane
Lipids and Steroids. Biochemistry by W.H. Freeman and Company.
Chapter 26. 6th Edition.
Cabrita MT, Vale C, Rauter AP. (2010). Halogenated compounds from
marine algae. J Nat, 8(8), 2301–2317.
Cuevas C, Francesch A. (2009). Development of Yondelis (trabectedin,
ET-743): a semisynthetic process solves the supply problem. Nat
Prod Rep, 26, 322–337.
Cuevas C, Perez M, Martin MJ, Chicharro JL, Fernandez-Rivas C,
Flores M, Francesch A, Gallego P, Zarzuelo M, de la Calle F. (2002).
Synthesis of ecteinascidin ET-743 and phthalascidin Pt-650 from
cyanosafracin B. Org Lett, 2, 2545–2548.
Demydchuk Y, Sun Y, Hong H, Staunton J, Spencer JB, Leadlay PF.
(2008). Analysis of the tetronomycin gene cluster: insights into the
biosynthesis of a polyether tetronate antibiotic. Chembiochem, 9,
1136–1145.
Fantini F, Barrantes F. (2009). Sphingolipid/cholesterol regulation of
neurotransmitter receptor conformation and function. Biochim
Biophys Acta, 1788. 2345–2361.
Fantini J, Garmy N, Mahfoud R, Yahi N. (2002). Lipid rafts: structure,
function and role in HIV, Alzheimer’s and prion diseases. Expert
Rev Mol Med, 4(27), 1–22.
Guo YQ, Warwick RM, Zhang ZN, Mu FH. (2002). Free living marine
nematodes as pollution indicator. J Environ Sci, 14(4), 558–62.
Harvey BM, Mironenko T, Sun Y, Hong H, Deng Z, Leadlay PF, Weissman
KJ, Haydock SF. (2007). Insights into polyether biosynthesis from
analysis of the nigericin biosynthetic gene cluster in Streptomyces
sp. DSM4137. Chem Biol, 14, 703–714.
Hentschel U, Usher KM, Tavior MVV. (2007). Marine sponges as
microbial fermentor. J Nat Prod, 16, 275–279.
Hill RT, Hamann MT, Peraud O, Kasanah N. (2004). Manzamine
Producing Actinomycetes. National center for natural product
research, USA. WO 2004/013297A3.
Hoshi M, Endo T. (2000). Microbial and chemical conversion
of antibiotic K41. II. Preparation of K41-DA1-DA2 and -DA3
deamicetosyl derivatives of antibiotic K41. J Antibiot (Tokyo). 53,
1154–1157.
Jayakumar R, Chennazhi KP, Anitha A, Ehrlich H, Tamura H, Nair SV.
(2010). Chitin of Marine Origin: Membranes, Scaffolds and Their
Biomedical Applications, Special issue marine functional food.
MDPI, 55(7), 675–709.
Kijjojoa A, Sawangwong P. (2004). Drugs and cosmetics from the sea.
J MDPI, 2, 73–82.
Kobayashi M, Natsume T, Tamaoki S, Watanabe J, Asano H, Mikami
T, Miyasaka K, Miyazaki K, Gondo M, Sakakibara K. (1997).
Antitumor activity of TZT-1027, a novel dolastatin 10 derivative.
Jpn J Cancer, 88, 316–327.
Luo C, Wang K, Liu D, Li Y, Zhao O. (2008). The functional roles of lipid
rafts in T cell activation, immune diseases and HIV infection and
prevention. Cell Mol Immunol, 5, 1–7.
Mikami Y, Takahashi K, Yazawa K, Arai T, Namikoshi M, Iwasaki S,
Okuda S. (1985). Biosynthetic studies on saframycin A, a quinone
antitumor antibiotic produced by Streptomyces lavendulae. J Biol
Chem, 260, 344–348.
Newman DJ, Cragg GM, Snader KM. (2000). The influence of natural
products upon drug discovery. Nat Prod Rep, 17, 215–234.

Newman DJ, Cragg GM, Snader KM. (2003). Natural products as a
source of new drugs over the period 1981–2002. J Nat Prod, 66,
1022–1037.
Newman SE, Eribulin. (2007). A simplified ketone analog of the tubulin
inhibitor halichondrin B, for the potential treatment of cancer.
Curr Opin Investig Drugs, 8, 1057–1066.
Ocio EM, Maiso P, Chen X, Garayoa M, Alvarez-Fernandez S, San-
Segundo L, Vilanova D, Lopez-Corral L, Montero JC, Hernandez-
Iglesias T. (2009). Zalypsis: a novel marine-derived compound
with potent antimyeloma activity that reveals high sensitivity of
malignant plasma cells to DNA double-strand breaks. Nature
Prod, 113, 3781–3791.
Oftedal L, Selheim F, Wahlsten M, Sivonen K, Døskeland SO, Herfindal
L. (2010). Marine cynobacteria contain apoptosis inducing activity
Critical Reviews in Microbiology Downloaded from informahealthcare.com by IBI Circulation - Ashley Publications Ltd on 07/12/11
synergizing with daunorubicin to kill leukemia cells but not
cardiomyocytes. J Nat Prod, 8(10), 2659–2672.
Pandey SC, Sassetti C. (2008). Mycobacterial persistence requires the
utilization of host cholesterol. Proc Natl Acad Sci, 105, 4376–4380.
Peng J, Hill R, Place A, Anklin C, Hamann MT. (2007). Marine microbes:
the critical role they play in sustainable production of starting
materials for the synthesis of drug leads and the structure for the
elusive Pfiesteria-associated fish killing toxin using 13C enrichment
and dual cryoprobe NMR studies. Papers, United States. 25–29.
Peng J, Kudrimoti S, Prasanna S, Odde S, Doerksen RJ, Pennaka HK,
Choo Y, Rao KV, Tekwani BL, Madgula V. (2010). Structure-activity
relationship and mechanism of action studies of manzamine
analogues for the control of neuroinflammation and cerebral
infections. J Med Chem, 53, 61–76.
Peng J, Place AR, Yoshida W, Clemens A, Hamann MT. (2010). Structure
and absolute configuration of karlotoxin-2, an ichthyotoxin from
the marine dinoflagellate Karlodinium veneficum. J Am Chem
Soc, 132, 3277–3279.
For personal use only.
Penseyan A, Kielleberg Egan S. (2010). Development of novel drugs
from marine microorganisms. Nature, 8(3), 438–59.
© 2011 Informa Healthcare USA, Inc.
View publication stats
Novel drugs from marine microorganisms  249
Place AR, Bai X, Kim S, Sengco MR, Coats DW. (2009). Dinoflagellate
host-parasite sterol profiles dictate karlotoxin sensitivity. J Phycol,
45, 375–385.
Place AR, Deeds JR. (2004). Dinoflagellate Karlotoxins, Methods of
Isolation and Uses Thereof. WO 2004/100659 A2. 21, 780–726.
Qadir MI, Malik SA. (2011). Genetic Variation in the HR Region of
the env Gene of HIV: A Perspective for Resistance to HIV Fusion
Inhibitors. AIDS Res Hum Retrovir, 27(1): 57–63.
Qadir MI, Malik SA. (2010). HIV Fusion Inhibitors. Rev Med Virol,
20:23–33. DOI: 10.1002/rmv.631
Rinehart (2000). Antitumor compounds from tunicates. Med Res Rev,
20, 1–27.
Rinehart KL, Bible V, Sakai KC, Sullins R, Li DW, Didemnins KM,
Tunichlorin. (1998). Novel natural products from the marine
Tunicates. J Nat Prod, 51, 1–21.
Scheuer PJ. (1996). Marine metabolites as Drug Leads Retrospect and
prospects: Colorado. J Nat, 1–12.
Sheng J, Malkiel E, Katz J, Adolf JE, Place AR. (2010). A dinoflagellate
exploits toxins to immobilize prey prior to ingestion. Proc Natl
Acad Sci, 107, 2082–2087.
Simons K, Ehehalt R. (2002). Cholesterol, lipid rafts and disease. J Clin
Invest, 110, 597–603.
Van Wagoner RM, Deeds JR, Satake M, Ribeiro AA, Place AR, Wright
JLC. (2008). Isolation and characterization of karlotoxin 1, a new
amphipathic toxin from Karlodimiun veneficum. Tetrahedron
Lett, 49, 6457–6461.
Wang D. (2008). Neurotoxins from marine dinoflagellates: a brief
review. Mar Drugs, 6, 349–371.
Yamada K, Okijia M, Kigoshi H, Suenaga, Kigoshi HS. (2000). Cytotoxic
substances from Opisthobranch molluscs, in drugs from the sea.
Basel, 59–73.
Zewail-Foote M, Hurley L, Ecteinascidin H. (1999). A minor groove
alkylator that binds DNA towards the major groove. J Med Chem,
42, 2493–2497.