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SCH 2443

NATURAL PRODUCT CHEMISTRY


DEPARTMENT OF CHEMISTRY, KULIYYAH OF SCIENCE

REVIEW PAPER: SPONGES AS PROMISING SOURCE FOR DRUG


DISCOVERY

Name Siti Nurhafizah Binti Ramli

Matric Number 1414146


Date of Submission 24/11/2016

Lecturer Assoc. Prof. Dr. Deny Susanti


INTRODUCTION

Natural Products are small molecules which are produced from plant, animals and
microorganisms. The availability of Natural Products may be limited depending on the
taxonomic species, genus species or organism. Natural Products are often recognized as
secondary metabolites which are the result of secondary metabolic pathway that does not
involve directly in growth, development, reproduction unlike primary metabolites towards
organism.

Recently, marine organisms have gained a lot of interest due to the promising variety
of secondary metabolites which are bioactive components laid within the marine species. One
of the marine species that exhibit high value of pharmaceutical properties is marine sponges.
Sponges as shown in the Figure 1 below are classified as marine invertebrate species belong
to the phylum of Porifera; “The Pore Bearers”. The animals that belong to the phylum consist
of tiny pores embedded on the wall of the body which became main reason why sponge is
characterized into the phylum.

Figure 1 : Morphology of sponges 1

Sponges are an example of the simplest form of multicellular aquatic organisms that
are fixed on the substrate and feed in by drawing water in and filter food particles sizing from
micron. In these few past decades, sponges is acknowledged as one of the most abundance
resources in discovering bioactive metabolites with respect to their diversity in primary and
secondary compounds embodied within the sponge. Some of the scientists raised a question
on how such organism could produce so many bioactive metabolites that could be used in the
development of new drugs. By looking at the structure of sponge, it could be deduced that
sponges may easily exposed to danger due to the threats from predator. To ensure their
survival, sponges produce a defence system by synthesizing bioactive components against
environmental stress factors such as predation, overgrowth by fouling organism or
competition for space in the marine ecosystem2.

This statement has also been acknowledged by a researcher from Flinders University,
Dr Jan Bekker as he is trying to identify new compounds from marine sponges that could
cure cancer and any other infectious diseases through chemically finger printing South
Australian Sea Sponges. He said in an interview,

"Sea sponges are sedentary, they don't move around, so over millennia they have evolved a
unique ability to produce chemicals to defend themselves from certain dangers in their
environment including diseases and other animals." 3

These chemicals released by the sponges are believed to exhibit potent


pharmaceutical values which can be applied in medical fields as well as contribute to diverse
human health benefits. The purpose of this paper is to discuss on the importance of secondary
metabolites from sponges for drug discovery as sponges are the secondary metabolites
isolated can function as:
a) Anti-tumour compounds
b) Anti-bacterial compounds
c) Anti-Malarial compounds
d) Immunosuppressives compounds
e) Anti-inflammatory compounds

This paper also aims to highlight the compounds according to their disease type and mode of
action which makes it useful in clinical research that leads to medical application of the
sponge derived products.

a) Sponges and Anti-tumour compound


According to a statement issued by World Health Organization (WHO), cancer is one
of the most potent diseases that can lead to death in most of developing countries. Cancer
cells are different from normal cells as they are

Sponges is believed to exhibit anti-tumour compounds as several compounds with


promising anti-cancer activity are isolated from different sponge species were found by the
natural product researchers. The anti-tumour compounds are Renieramycins, Monanchocidin,
Smenospongine, lactin and heteronemine and others. The valuable compound with promising
anti-cancer activity is Renieramycins which is isolated from several genera of sponges such
as Reneira sp. And Xestospongia sp. This compound; a type of tetra-hydro-isoquinolines, a
form of alkaloid is believed to have capability to suppress the action of tyrosine phosphatase
receptor type K (PTPRK) in HCT-116 and MDA-MB-435 cancer cell lines 4 .

A pre-clinical result was conducted to observe the ability of this compound in


suppressing lung cancer development. The trial had proven that this bioactive components
help to induce the apoptosis of lung cancer cells via p-53 pathway and inhibit the progression
and metastasis of lung cancer 5. The structure of Renieramycins is displayed in Figure 2

Figure 2: Structure of Renieramycins 1

Heteronemin isolated from Hyrtios sp. of sponge is a type of terpenes from classes of
sesterterpenes with C25 number of carbons. This compound has attracted scientists’ interest as
it shows great potency as anti-tumour agent as it shows significant effects on myelogenous
leukimia cells. Heteronemin exhibits great potential in promoting apoptosis of cell, mitogen-
activated protein kinases (MAPKs) pathway and signalling cascade of the nuclear factor
kappaB 1. The structure of heteronemin can be seen in figure below.

Figure 3: Structure of heteronemin1

b) Sponges as anti-bacteria compound.

Sponges are constantly facing the infection from water-borne microbes including
pathogens and fouling microorganism. Despite of their simple and multicellular organism
without true layer of organs, yet it is surprisingly that the simple organism with lacking in
morphological and cellular defence can withstand the bacterial infection. The impressive
defence system of sponges has attracted researchers’ interest in isolating the. Nowadays,
diseases caused by microbes such as malaria, tuberculosis, gonorrhoea have become major
concern in the public health problem. These microbes have become resistant towards
antibiotic drugs and difficult to be treated 6,7.

One of the significant antibiotic compounds isolated from actinomycetes bacteria on


marine sponge. Almost 70% of the antibiotic compounds are isolated from the actinomycetes.
The bacteria is considered one of the most largest taxonomic units identified within the
Bacteria domain in line with 18 major lineages 8. These bacteria are acknowledged to play
major role in the production of antibiotic due to the high Guanine and Cytosine content in the
deoxyribonucleic acid (DNA) 9.

In these past few years, the discovery of antimyocetes in terrestrial region has
depleted and causes a concern among researchers. As an alternative, they are diverting their
attention to marine products especially sponge as they noticed the remarkable content of
bacteria and cyanobacteria associated with marine sponge as the new source or antibiotic 10.
One of the sources of actinomycetes is discovered from Dendrilla nigra sp collected from
Vizhinjam coast which is located within the West Coast of India 11.

The species is identified to possess an amount of actinomycete strains. The strain


identified is from Nocardiopsis dassonvillei MAD08 which exhibit significant anti-bacterial
activity against the attack from pathogen. dassonvillei MAD08 which exhibit significant anti-
bacterial activity against the attack from pathogen. Aside from the strain mentioned,
Streptomyces sp. BLT7 isolated from the Dendrilla nigra sp also exhibit the anti-bacterial
properties12. The unique ability of these strains as a contributor to the defense system of
sponge has led to a discovery of new drugs.

c) Sponge and anti-malarial compound

Malaria is an infectious disease that is caused by Plasmodium from the genus of


protozoa. The parasite is transmitted through biting by the female Anopheles mosquitoes.
Once the victim has been bitten by the mosquitoes, the parasite will enter human system and
invade red blood cells and carried through the liver. The invasion by the parasite will cause
red blood cell to burst which later develop the malaria symptoms. This disease has been a
threat to human kind as there are more than 200 million new cases of infection reported each
year worldwide. In ratio, the disease is reported to cause 1 million to 2.5 million deaths per
annum13.

Unfortunately, the drugs used to treat the malaria disease are limited. Due to this
limitation of drugs available, it had been reported that number of deaths were increasing in
sub-Saharan African countries and they were constantly exposed to the threat of plasmodium
strains which causes malaria14, 15. Recently, plasmodium strains have displayed resistance
toward chloroquinone, pyrimethamine and sulfadoxine. With increasing resistance of
Plasmodium strains, the issue has caused concerns among researchers which trigger the need
to develop new drugs as new anti-malarial compound.

The potential of bioactive components isolated from marine sponges as anti-malarial


has been discovered. A study was conducted on Axinyssa differi sp. of Senegalese sponge
which lives in the specific biotope of African mangrove. The researchers discovered that the
Axinyssa differi sponge produced a series of glycosphingolipids compounds together with
three new isolated compounds of axidjiferosides from the genera of Leishmania and
Trypanosoma. This unique discovery of axidjiferosides has displayed a great potential in
inhibiting Plasmodial strains activity. The anti-plasmodial activity displayed by
axidjiferosides shows low cytotoxicity towards human cells. Thus, this compound exhibit
anti-malarial properties and can be used to treat malaria disease16.

d) Sponges and immunosuppressive compound

There has been an increasing demand in organ transplanting. The only drawback in
organ transplanting is the possibility of the body to reject the transplant organs such as heart,
kidney and liver. The body will recognize the transplanted organ as a foreign object thus
triggering the immune system to invade the foreign mass. To prevent such problem to
happen in future, every person who are performing organ transplant will receive
immunosuppressant drugs to minimize the action of immune system by weakening the action
and allowing the body to accept the foreign mass.

Patients who are receiving transplant organ will continuously need a supply of
medicine to prevent rejection of immune system towards the organ. Thus, it is crucial to
develop specific suppressor drugs and researchers have been constantly finding a way to
develop the drug to meet up the demand in discovering new immunosuppressant drugs. One
of the potent sources in developing the drug is from sponges.

Dysidea sp. of sponge family found in the sea of North Australia offers promising
discovery of immunosuppressive compounds as it possess three polyoxygenated sterols.
These compounds exhibits strong selective immunosuppressive activity in inhibiting the
binding on cytokinie of interleukin 8 (IL-*) which has high affinity towards nucleophilic
attack. These polyoxygenated sterols show high selectivity in preventing immune system
response towards foreign mass in the body17. Aside from the bioactive components isolated
from Dysidea sp., some immunosuppressive compounds are discovered from Carribean
sponge. Plakortis simplex, a form of glycolipid simplexides are isolated which significantly
inhibit proliferation of activated T-cells through a non-cytotoxic mechanism.

e) Sponge and anti-inflammatory compounds

The common cause of inflammation is due to the secretion of chemicals from tissues
and cells. The chemicals that induce inflammation are commonly known as leukotrienes,
prostaglandins, histamine, bradykins and many more18. These compounds are derived from
archidonic acid when released in the body facilitate by enzymatic reaction will cause the
inflammation to occur. Thus, it is necessary to develop anti-inflammatory drugs to prevent
this problem from occurring.

Monoalide from sponge has been acknowledged to exhibit potential anti-


inflammatory properties. Figure below depicted the anti-inflammatory action of monoalide
from sponge. An enzyme called phospholipase L2 (PLA2) catalyse the synthesis of free
mobile archidonic acid denoted by AA. The acid is then modified to the leukotrienes and
prostaglandin. The conversion is catalysed by the enzyme lipooxygenase (LOX) and
cyclooxygenase-2 (COX-2). The anti-inflammatory compound resided in sponge aid in
inhibiting the action of LOX and PLA2. NSAID is denoted for non-steroidal anti-
inflammatory drugs which facilitate in inhibition of COX-2 and COX-119. This inhibition of
COX enzyme will cease the formation of leukotrienes and prostaglandins and suppressing the
inflammation.

Figure 4: Anti-inflammatory action of sponge 18


CONCLUSION

As the sources of bioactive compounds in terrestrial part has depleted, researchers are
diverting their attention to the marine sources of drugs as marine environment are rich with
biotechnological properties such as anti-inflammatory, anti-tumour, anti-viral and others
especially sponges. Marine organisms have been acknowledge in contributing to the
formulation of therapeutical drugs as they produce large amount of natural products and
secondary metabolites.

The sponges are exceptional store house of valuable bioactive compounds. They are rich with
bioactive compounds with unique structural and chemical properties that are not found in
terrestrial natural products. The ability of sponges to withstand threats from pathogens and
bacterial infection with lacking in defence system has trigger marine natural product
researchers to discover what components available in the sponge that made it to exhibit that
behaviour.

Unfortunately, the valuable secondary metabolites in sponge are found in small quantity and
cause a concern among the researchers. Therefore, to sustain the development of widely
available and useful medicine, there is a need in a quest of synthetically produced the
compounds. This will help to produce the medicine in a large scale and benefit to all. This is
the important quest after discovering valuable compound in sponge.

In Islamic perspective, Allah had mentioned in the Holy Quran,


“And He has made everything in the heavens and everything on the earth subservient to
you.It is all from Him. There are certainly signs in that for people who reflect.’ (Surat al-
Jathiyya, 13)

Nobody would expect that the simplest form of multicellular organism like sponge would
exhibit such valuable therapeutical properties that would develop a deep study in evaluating
the pharmaceutical properties. Indeed, Allah knows the best and He create things with
amazing qualities only for those who thinks.

REFERENCES

1) Van Soest, R. W. M., Boury-Esnault, N., Vacelet, J., Dohrmann, M., Erpenbeck, D., de
Voogd, N. J., Hooper, J. N. A. (2012). Global diversity of sponges (Porifera). PLoS ONE,
7(4). http://doi.org/10.1371/journal.pone.0035105

2) Perdicaris, S., Vlachogianni, T., & Valavanidis, A. (2013). Natural Products Chemistry
& Research Bioactive Natural Substances from Marine Sponges : New Developments and
Prospects for Future Pharmaceuticals, 1(3), 1–8.

3) Sea sponges offer hope for new medicines. (2012). Retrieved November 10, 2016, from
http://phys.org/news/2012-10-sea-sponges-medicines.html
4) Charupant K, Suwanborirux K, Daikuhara N, Yokoya M, Ushijima-Sugano R, Kawai T,
Owa T, Saito N. Microarraybased transcriptional profiling of renieramycin M and
jorunnamycin C, isolated from Thai marine organisms. Mar Drugs 2009; 7: 483-494.
5) Halim, H., Chunhacha, P., Suwanborirux, K., & Chanvorachote, P. (2011). Anticancer
and antimetastatic activities of renieramyein M, a marine tetrahydroisoquinoline alkaloid,
in human non-small cell lung cancer cells. Anticancer Research, 31(1), 193–201.
6) Research, C. for D. E. and A. (n.d.). Antibiotics and Antibiotic Resistance. Retrieved
November 2, 2016, from
http://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/A
ntibioticsandAntibioticResistance/default.htm

7) Common Marine Sponges May Provide Super-antibiotics Of The Future - ScienceDaily.


(2009). Retrieved November 2, 2016, from
https://www.sciencedaily.com/releases/2009/02/090226110743.htm
8) Stackebrandt S (2000) The prokaryotes: an evolving electronic resource for the
microbiological community. Springer, New York
9) Yoshida A, Seo Y, Suzuki S, Nishino T, Kobayashi T, Hamada-Sato N, Kogure K, Imada
C (2008) Actinomycetal community structures in seawater and freshwater examined by
DGGE analysis of 16S rRNA gene fragments. Mar Biotechnol 10(5):554–563
10) Piel J, Hui D, Wen G, Butzke D, Platzer M, Fusetani N, Matsunaga S (2004) Antitumor
polyketide biosynthesis by an uncultivated bacterial symbiont of the marine sponge
Theonella swinhoei. Proc Nat Acad Sci USA 101(46):16222–16227
11) Kim, S. K. (2015). Handbook of anticancer drugs from marine origin. Handbook of
Anticancer Drugs from Marine Origin, (November 2016), 1–805.
http://doi.org/10.1007/978-3-319-07145-9
12) Selvin J, Joseph S, Asha K, Manjusha W, Sangeetha V, Jayaseema D, Antony M, Denslin
Vinitha A (2004) Antibacterial potential of antagonistic Streptomyces sp. isolated from
marine sponge Dendrilla nigra. FEMS Microbiol Ecol 50(2):117–122
13) Crutcher JM, Hoffman SL. Malaria. In: Baron S, editor. Medical Microbiology. 4th
edition. Galveston (TX): University of Texas Medical Branch at Galveston; 1996.
Chapter 83. Available from: https://www.ncbi.nlm.nih.gov/books/NBK8584/
14) Bell, D.R.; Jorgensen, P.; Christophel, E.M.; Palmer, K.L. Malaria risk: Estimation of
the malaria burden. Nature 2005, 437, E3–E4
15) Petersen, I.; Eastman, R.; Lanzer, M. Drug-resistant malaria: Molecular mechanisms
and implications for public health. FEBS Lett. 2011, 585, 1551–1562.
16) Farokhi, F., Grellier, P., Clément, M., Roussakis, C., Loiseau, P. M., Genin-Seward, E.,
Wielgosz-Collin, G. (2013). Antimalarial activity of axidjiferosides, new β-
galactosylceramides from the African sponge Axinyssa djiferi. Marine Drugs, 11(4),
1304–1315. http://doi.org/10.3390/md11041304
17) de Leone PA, Redburn J, Hooper JNA, Quinn RJ(2000) Polyoxygenated Dysidea sterols
that inhibitthe binding of [I125] IL-8 to the human recombinant IL-8 receptor type A. J
Nat Prod 63, 694–697
18) Vane, J., & Botting, R. (1987). Inflammation and the mechanism of action of anti-
inflammatory drugs. The FASEB Journal , 1 (2 ), 89–96. Retrieved from
http://www.fasebj.org/content/1/2/89.abstract
19) Anjum, K., Abbas, S. Q., Shah, S. A. A., Akhter, N., Batool, S., & Hassan, S. S. U.
(2016). Marine sponges as a drug treasure. Biomolecules and Therapeutics, 24(4), 347–
362. http://doi.org/10.4062/biomolther.2016.067