How Marine Animals Are Used For Medicine

• Journal Listing
• J Pharm Bioallied Sci
• v.viii(2); Apr-Jun 2016
• PMC4832911

J Pharm Bioallied Sci. 2016 Apr-Jun; viii(2): 83–91.

Exploring the body of water for new drug developments: Marine pharmacology

Harshad Malve

Atomic number 82 Medical, Asia Pacific Region, Ferring Pharmaceuticals Pvt. Ltd., Elphinstone (Westward), Bombay, India

Received 2015 Jun five; Revised 2015 Jul 11; Accepted 2015 Jul 25.

Abstract

Disease ailments are changing the patterns, and the new diseases are emerging due to changing environments. The enormous growth of world population has overburdened the existing resources for the drugs. And hence, the drug manufacturers are always on the lookout for new resources to develop effective and safe drugs for the increasing demands of the earth population. Seventy-5 percentage of world's surface is covered by water only research into the pharmacology of marine organisms is limited, and virtually of it still remains unexplored. Marine environment represents endless and diverse resource for new drugs to combat major diseases such as cancer or malaria. It too offers an ecological resource comprising a diversity of aquatic plants and animals. These aquatic organisms are screened for antibacterial, immunomodulator, anti-fungal, anti-inflammatory, anticancer, antimicrobial, neuroprotective, analgesic, and antimalarial properties. They are used for new drug developments extensively beyond the world. Marine pharmacology offers the telescopic for research on these drugs of marine origin. Few institutes in India offer such opportunities which can help us in the quest for new drugs. This is an extensive review of the drugs developed and the potential new drug candidates from marine origin along with the opportunities for research on marine derived products. It also gives the information about the institutes in India which offer marine pharmacology related courses.

KEY WORDS: Anticancer, bryostatin, cytarabine, keyhole limpet hemocyanin, mariculture, sponge, ziconotide

Ocean represents a source of a varied type of organisms due to the diversified environs offered past unlike oceanic zones. The enormous ecological resources of the body of water have been exploited since ancient times and included the employ of marine animals similar fish and preparations from algae as the sources of medicine. Fish oils are the classic case of marine-derived product in use since ages. Marine pharmacology is a branch of pharmaceutical sciences which focuses on the substances with active pharmacological properties nowadays in marine species of plants and animals. Marine surroundings is an exceptional shop house of novel bioactive natural products, with structural and chemic features generally not found in terrestrial natural products. The marine organisms besides provide a rich source of nutraceuticals and potential candidates for the handling of several homo diseases. The modern day focus of marine pharmacology is on microbes.[1] This includes the discovery of new pharmaceutical candidates from marine microbes.[two] The body of water provides enormous opportunities to discover new compounds equally it has more than 13,000 molecules described out of which 3000 are having active properties.[iii] Marine natural products are mostly secondary metabolites. They are not generated past biological or regular metabolic pathways and take no primary function associated with the development, growth, or propagation of a species.[iv] Sixty-three percentage of the new drugs are classified as naturally derived (i.east., modified natural production, unmodified natural product or synthetic compound with a natural product as pharmacophore). Covering the menstruation from 1981 to 2008, around 68% of all the drugs used to adjourn infection (including antibacterial, antiviral, antiparasitic, and antifungal compounds) and 63% of anti-cancer drugs were naturally derived.[five]

Biodiversity of Marine Environment

Marine environment is a natural habitat for a broad variety of living organisms having dissimilar physiology and capacity to adapt their environment. Out of over 33 animal phyla known today, a total of 32 phyla are embodied in the marine environment out of which 15 varieties are exclusively present in the marine environment.[6] Such genetic diversity renders chemical diverseness which is promising for new drug development.

Oceans contain more than than fourscore% of various plant and animal species in the world. Marine organisms such equally sponges, tunicates, fishes, soft corals, nudibranchs, sea hares, opisthobranch Molluscs, echinoderms, bryozoans, prawns, shells, sea slugs, and marine microorganisms are sources of bioactive compounds (viz. oils and cosmetics).[vii] The starting time biologically agile marine natural production was formally reported in late 1950 by Bergmann.[8] In tardily 1970, information technology was established that marine plants and animals are genetically and biochemically unique. Around 15,000 such unique natural compounds have been described and out of them 30% products have been isolated from sponges.[9] The remarkable discovery of unusual arabino-or ribo-pentosyl nucleosides in marine sponges was the offset illustration that is naturally occurring nucleosides could comprise sugars other than ribose and deoxyribose.[10] It was as well observed that molecules of marine origin can exist accepted by humans with minimal manipulation.[3]

There are some reports on the characterization of the antimicrobial activity of marine macroorganisms collected from the Indian coastline have appeared. Streptomyces sp. has been the most widely studied microbial species from the Indian littoral waters as a source of antibiotics.[11] In a study, 75 bacterial strains from 4 species of marine sponges were isolated, out of which 21% of the isolates have shown practiced antibacterial action, with some of the strains showing species specificity.[11] The written report indicated the diversity of antibiotic producing marine bacteria and also established that sponges are a rich source of bacteria capable of producing novel pharmacologically active molecules.

Marine Pharmacology in India

India has over 8000 km of coastline with clusters of marine habitats like inter-tidal rocky, muddy and sandy shores, coral reefs, and mangrove forests. The potential of Indian marine habitat has remained largely unexplored for their potential of new drugs and biotechnological programs. Some of the selected institutes such equally National Institute of Oceanology, Goa; Central Drug Inquiry Constitute, Lucknow; Bose Found, Kolkata; Key Establish of Fisheries Education, Mumbai; Regional Inquiry Laboratory, Bhubaneswar of Council for Scientific and Industrial Research are before long working for exploration of life saving drugs from marine sources. Many other Indian institutes, universities, and pharmaceutical companies have also recognized the significance of this subject.[12]

Marine pharmacology has been reviewed extensively in the by all over the world as well as in India, simply still there is a need to review the potential of the oceans equally source for the evolution of new drugs, considering the advantage of their abundance in nature and large scale production. At present, the drug industry is working on screening and isolation of novel molecules with unreported pharmacological backdrop that can be exploited for the development of new therapeutic agents for commercial use. This review has largely focused on different classes of marine drugs currently in utilise and at different stages of trials for approval and marketing in time to come. The review has likewise tried to delve into the limitations and future trends of the drugs from marine sources.

Nomenclature of Marine Pharmacology

Marine pharmacology can be classified on the basis of source of the candidate drug[nine]

• Genetically engineered marine organisms

• Manufacture of pharmaceuticals and nutraceuticals of marine origin

• Chemicals produced past or found in marine organisms shown to have a wide variety of applications as pharmaceuticals.

Marine drugs tin can be broadly classified based on their actions as follows:

Antibacterial

Eicosapentaenoic acid, a polyunsaturated fatty acrid, isolated from a diatom of marine origin Phaeodactylum tricornutum which has shown activity confronting an assortment of Gram-positive and Gram-negative leaner, which also includes a multidrug-resistant variety of Staphylococcus aureus.[13]

Anti-inflammatory

The anti-inflammatory function of extracts and other parts of a Mediterranean sponge species Spongia officinalis in the in vivo report on rat model of carrageenan-induced paw edema assay.[xiv]

Neuroprotective

The extracts of South Indian greenish seaweed Ulva reticulata has shown neuroprotection by inhibiting acetyl-and butyryl-cholinesterases, efficacy comparable to agents currently canonical for Alzheimer'south disease treatment.[15]

Antiparasitic

Extracts of Sarcotragus sp. known as Tunisian sponge prepared in dichloromethane has demonstrated in-vitro anti-leishmanial action by demonstrating the associated morphological alterations in promastigotes of leishmania major.[xvi]

Antiviral agents

Anti-herpes simplex virus-i (HSV) action found in high molecular weight exo-polysaccharides extracted from the Celtodoryx girardae (French marine sponge) and its associated symbiotic bacteria has been reported.[17]

Anticancer

Bryostatin, primarily obtained from the Bryozoan, Bugula neritina, although some forms have been extracted from sponges and tunicates. Sorbicillin-derived alkaloids sorbicillactone A and its 2', 3'-dihydro analog sorbicillactone-B has shown activeness against leukemia cells free from any noteworthy cytotoxicity. Sorbicillactone-B has been derived from a salt-water culture of a bacterial strain Penicillium chrysogenum which has been isolated from a sponge Ircinia fasciculata, a Mediterranean sponge specimen.[18]

Another promising anticancer drug used every bit an immunotherapeutic agent is keyhole limpet hemocyanin (KLH). KLH is a copper containing extracellular respiratory protein present in Megathura crenulata, a marine Gastropod species found in large numbers at the Pacific coast of California and Mexico. KLH is constitute in two isoforms KLH1 and KLH2.[19] KLH is reported to possess remarkable immunostimulatory properties in experimental animals and human, used in experimental immunology and too clinically as an immunotherapeutic agent.[20] KLH is specifically used in clinical setup for the treatment of bladder carcinoma, and its efficacy is peradventure due to a cross-reacting saccharide epitope. KLH may also have significant potential for the treatment of other types of cancers, particularly the adenocarciomas derived from the epithelium, by using it every bit a carrier for gangliosides of carcinoma and mucin-like epitopes.[xix]

KLH is intravesically administered to patients with bladder carcinoma. Its clinical success in carcinoma patients is attributed to the presence of the disaccharide epitope Gal (β1-3), Ga1NAc.[21] This epitope of KLH is believed to exist cross-reactive with an equivalent epitope on the urinary float tumor cell surface. The cumulative cellular and humoral immunological responses to KLH can result in a cytolytic reduction of tumor growth.[xix]

In add-on to tumor immunotherapy, KLH is also prescribed in the following conditions:[19]

1. As a generalized vaccine component for antigen presentation, solitary or in adjuvant cocktail

2. For diagnosis of schistosomiasis considering of cantankerous-reactivity to one of the epitopes on larval schistosomes

3. In drug assays

4. Handling of drug addiction by immunoassay for driveling drugs

5. For immune competence testing

6. Assessment of stress and inflammation.

Analgesic

Ziconotide was the first drug of marine origin to obtain approving from the U.S. Nutrient and Drug Assistants (USFDA) in 2004 to treat pain. It is also known as Prialt, and it was originally extracted from the marine snail Conus magus. Results from animal studies suggested the role of ziconotide in blocking of N-type calcium channels on the chief nociceptive nerves of the spinal cord.[22]

Antimicrobial

The cephalosporins are well-known antimicrobial agents with a marine source of origin. Cephalosporin C was firstly extracted and purified from a marine fungus, Cephalosporium acremonium.[9]

Antimalarial activeness

Isonitrile containing antimalarial molecules have been extracted from the Acanthella sp., a Japanese sponge. The isolated molecules belong to kalihinane diterpenoids class, which besides contains antifungal, anthelmintic, and antifouling compounds.[23]

Evolution of Marine Pharmacology

The recent global marine, pharmaceutical pipeline consists of only 3 USFDA approved drugs, and one European Spousal relationship (EU) registered drug. Currently, marine drugs in the clinical lineup accept 13 compounds that are at different stages of clinical trials, with a very large number of marine-derived compounds/molecules in the preclinical testing pipeline as well.[2]

The iii Nutrient and Drug Administration (FDA) approved the marine-derived drugs currently used in the Us are, cytarabine (Cytosar-UW, DepocytW), vidarabine (Vira-AW), and ziconotide (PrialtW). Various marine drugs in unlike phases of clinical trials are summarized in Tabular array 1.[2]

Tabular array ane

A perspective of pipeline of marine drugs

Canonical drugs of marine origin

Some of the drugs of marine origin canonical for man utilize in different parts of the world are as follows:

Cytarabine (cytosine arabinoside or arabinosyl cytosine, ara-C)

Cytarabine is a synthetic pyrimidine nucleoside derived from spongothymidine and primarily isolated from a Caribbean sponge species Tethya crypta. It is FDA approved and mainly used in unlike types of leukemia, including acute myelocytic leukemia, lymphocytic leukemia, meningeal leukemia, and smash crisis phase of chronic myelogenous leukemia.[2]

Vidarabine (adenine arabinoside, ara-A or arabinofuranosyladenine)

Vidarabine is a constructed purine nucleoside isolated from the Caribbean area sponge T. crypta and developed from spongouridine is currently obtained from Streptomyces antibioticus. Information technology is approved by FDA for use in recurrent epithelial keratitis acquired by HSV) type one and 2, acute kerato-conjunctivitis, and also for superficial keratitis.[2]

Ziconotide

Ziconotide is a synthetic molecule, equivalent to a natural 25-amino acid peptide, v-conotoxin MVIIA. It is originally extracted and purified from the venom of marine snail C. magus, which is a fish-hunting species. Ziconotide has shown potential every bit an analgesic with a novel mechanism of action.[ii] Information technology is approved equally an analgesic by FDA.

Trabectedin

A marine natural production extracted from a tunicate species Ecteinascidia turbinata generally inhabitant of Mediterranean and Caribbean area Sea. Trabectedin molecule is an alkaloid of tetrahydroisoquinoline class, and it was the first anticancer molecule of marine origin got approval in European union for utilise in the treatment of soft-tissue sarcoma and in relapsed cases of platinum-sensitive ovarian cancer.[ii]

Marine Drugs in Clinical Phase Three Trial

Eribulin mesylate (E7389) or halichondrin B

It is a polyether macrolide natural molecule originally extracted from marine sponges, with stiff anticancer activeness reported in preclinical brute models. Eribulin is a stiff molecule which produces irreversible antimitotic activeness leading to cell death past apoptotic pathway.[2] On-going Stage III studies are evaluating the comparative clinical efficacy of eribulin versus capecitabine and eribulin versus other preferred handling option.

Soblidotin (auristatin PE or TZT-1027)

Is a constructed derivative of the dolastatin backbone from dolastatin 10. Information technology is a vascular disrupting agent causing the collapse of the vasculature inside the tumor, in add-on to its tubulin inhibitory action. This drug is undergoing trials in clinical Phases I, Ii, and Iii with different companies who are trying to use information technology every bit a weapon to specific monoclonal antibodies linked via customized peptides.[two]

Tetrodotoxin

A very well known "marine toxin," and highly substituted guanidine-derivative.[24] It is not an anti-tumor amanuensis, currently in Phase III trials as analgesic against inadequately controlled pain related to the cancer. A Phase II trial is ongoing to assess the efficacy of tetrodotoxin confronting the neuropathic pain related to chemotherapy-induced peripheral neuropathy.[25]

Marine-Derived Compounds in Clinical Phase II Trial

DMXBA (GTS-21) [3-(2,iv-dimethoxybenzylidene)-anabaseine; GTS-21]

Information technology is a synthetic imitative of anabaseine, which is an alkaloid establish in many species of aquatic worms of phylum nemertea. DMXBA is reported to be beneficial for the central nervous organisation, improves cognition and sensory gating deficiency in a diversity of laboratory animals.[2] A recent clinical trial of the molecule in Phase II with schizophrenic patients has shown noteworthy improvement in cognitive functions.[2]

Plitidepsin

It is a natural marine depsipeptide, currently obtained by total synthesis. It was primarily isolated from a tunicate Aplidium albicans found in the Mediterranean Ocean. Plitidepsin is a highly strong apoptosis inducer with low nanomolar (nM) range of IC_fifty values. The major toxicity found with most schedules of plitidepsin were muscle toxicity, an increment of transaminases, general fatigue, diarrhea, and cutaneous rash.[2]

Elisidepsin (PM02734)

It is a novel cyclic peptide derived from marine sources and belongs to the Kahalalide family of compounds. It is currently undergoing development in Phase Ii with primary evidence of antitumor potency with encouraging therapeutic index.[2] It has shown potent in vitro cytotoxic activeness against diverse human being tumor cell lines, which may be because of oncolytic jail cell death induction instead of apoptotic cell expiry.[2]

PM00104 (Zalypsis)

Information technology is a novel alkaloid with DNA-bounden chapters. It is linked to jorumycin extracted from the Pacific nudibranch'south (Jorunna funebris) skin and mucus as well as from renieramiycins extracted from varieties of sponges and tunicates. Preclinical in vivo studies washed earlier with these molecules indicated considerably high antitumor activity in cells of breast, prostate and renal cancers with a modest antitumor activity on colon cancer cells. Reversible hematological disorders or liver enzymes imbalance were the main toxicities constitute to be associated with Zalypsis treatment during the Phase I trials.[2]

Plinabulin (NPI-2358)

It is a fully laboratory made analog of the natural product halimide originally derived from marine Aspergillus sp. CNC-139 (from Halimeda lacrimosa) and phenylahistin extracted from Aspergillus ustus.[ii] Information technology functions past inhibiting the polymerization of tubulin, which leads to destabilization of the vascular endothelial compages of the tumor.[26]

ILX-651 (tasidotin or synthadotin)

Its a constructed derivative of dolastatin-15 and it inhibits associates of tubulin.[two] It is an orally active drug and has progressed to Phase Ii trials in dissimilar types of cancer. ILX-651 is also under study in preclinical stages for exploring the routes and targets of its deportment, including its use in advanced stage refractory neoplasms.[2]

Pseudopterosins

A leading class of diterpene glycosides primarily extracted from the octocoral Pseudopterogorgia elisabethae.[2] Pseudopterosin A is a stiff phorbol myristate acetate inhibitor, reported to crusade topical inflammation in a mouse model with degranulation of homo polymorphonuclear leukocytes and prevents phagosome cosmos in tetrahymena cells. In a double-bullheaded, Stage 2 clinical trial, pseudopterosins were found to augment re-epithelialization process with qualitative enhancement in the early wound repair process.[2]

Marine Drugs in Clinical Stage I Trial

Leconotide (AM-336, ω-conotoxin CVID)

It is a peptide having 27 residues containing 3 CYS-CYS bonds. It is like to Ziconotide and is undergoing Phase I trials for the treatment of cancer. Although, in initial studies, it is used through intrathecal route (as ziconotide),[27] currently the systemic administration is done.[28,29]

Enfortumabvedotin

It is used in immunotherapy and it is a combination of a fully human IgG1k antibody and monomethyl auristatin Due east. It is also known under the code names of AGS-22MSE and AGS-22ME and reported to be currently in a Phase I trial.[23]

Vorsetuzumab mafdotin (SGN-75)

An antibiotic-drug cohabit, with monomethyl-auristatin F attached to the anti-CD70 monoclonal humanized antibody 1F6.[thirty] This molecule is currently being evaluated for its efficacy in relapsed and refractory non-Hodgkin's lymphoma in Phase I clinical trials and also in metastatic renal cancer with CD70 epitope expressing cancer cells.[31]

Bryostatin 1

It has in vivo biological agile molecule bryostatin 3 (one of the 20 known varieties) isolated from the bryozoan B. neritina. Since the twelvemonth 2007, at least four Phase I and eight Stage II trials with bryostatin against multiple carcinomas have been reported, with all the studies using a combination with biologicals or cytotoxins. Bryostatin is currently undergoing two Phase I trials for assessment equally a treatment for Alzheimer's disease.[2]

Hemiasterlin (E7974)

It'due south a cytotoxic tripeptide molecule, originally isolated from marine sponges.[2] Dose-limiting toxicities such as neutropenia/febrile neutropenia along with another adverse events such as full general fatigue, nausea, vomiting sensation, and constipation, were reported in the Stage I studies.[2]

Marizomib (NPI-0052, salinosporamide A)

It is a natural compound derived from marine actinomycete Salinispora tropica. Marizomib is a potent and selective inhibitor of the proteasome; a multicatalytic enzyme complex found to be associated with the degradation of nonlysosomal proteins plant in cells making it a proven target for the handling of cancer.[2] Translational biology studies established marizomab activeness as a single therapeutic chemical compound against the solid tumor and hematological malignancies (e.g., multiple myelomas). Later studies confirmed the potential of marizomib utilize in combination with chemotherapy and/or biologics.[two]

Preclinical Pipeline

The preclinical drug pipeline plays an important role and currently supplying hundreds of novel marine natural compounds postsafety screening every year and continue to support the clinical pipeline with potentially valuable compounds. Since 1974 (when FDA canonical 3 marine drugs), information technology required over 30 years for any other natural product of marine origin to become approved for clinical use.

In the final 5 years, preclinical pharmacology of 262 marine compounds has remained nether various stages of study spreading over 35 countries including the U.s.a., they are now part of the preclinical pharmaceutical pipeline.[32] Promising antibacterial, antifungal, antiprotozoal, antitubercular, and antiviral activities accept been reported for 102 natural marine compounds.[32] As reported by Mayer et al., effectually 60 marine compounds have been constitute to have a potency of immune and nervous systems, some anti-diabetic and anti-inflammatory effects accept besides been observed. Finally, 68 promising molecules extracted from marine sources were constitute to collaborate with an array of molecular targets and receptors, which may probably contribute to develop various pharmacologically active classes of drugs upon more focused studies for confirmation of their mechanism of action.[32] The important agents from the preclinical pipeline are also summarized in Table 1.

Anticancer Drugs Developed from Marine Origin: Hope for Future

Targeting the diverse indicate transduction pathways involved in carcinogenesis is i of the best treatment strategies for cancer. Some inhibitors of these pathways derived from the marine organisms have been re-designed, and further studies were done to offset tumor progression and curtail carcinogenesis.[33] Modernistic anticancer drugs discovery is looking for cytotoxic agents with improved accuracy, efficacy with target specificity and sensitivity.

Co-ordinate to an guess by Sawadogo et al., in 2011 bachelor promising anticancer compounds of marine origin tin can be divided into different classes of chemicals majority represented by terpenes and terpenoids (40.5%) following past peptides (xix%), macrolides 14.3%), and alkaloids (12%). Amongst them, l% are 1^st fourth dimension looked upon as anticancer agents. The bulk of these compounds are chemotherapeutic agents (92.seven%), and only 7.3% are chemopreventives, which are known every bit nutraceuticals available in vegetables and fruits.[34] The biological mechanisms involved in the anti-cancer properties of the investigated compounds in Sawadogo et al. study are mainly prison cell bicycle abort through tubulin inhibitory upshot; apoptosis through the various mechanisms such every bit caspases 3, 8, 7, and 9 activation, MMP depolarization, bib truncation, Bcl-twoscore, Bax and poly(ADP-ribose) polymerase cleavages; anti-migratory upshot through specific inhibitory upshot on TRPM7 channels, anti-angiogenic holding past inhibition of vascular endothelial growth gene-A secretion; anti-inflammatory issue through the inhibition of COX-ii and iNOS expression.[34] Looking at the possibility of a large number of therapeutic compounds, it may be possible to find out drugs of marine origin for targeted therapy of cancer which is non possible until at present with much success.

Challenges and Future Trends

There are certain major challenges to derive the drugs from marine sources. The variable environmental weather condition could result in the product of different metabolite every time from the same organism. A major claiming sometimes faced is that the microorganisms residing in the marine animal, and not the invertebrate marine hosts really produces the bioactive molecules.[4] Sustainable supply of isolated and identified atomic number 82 compounds sometimes pose a problem because the lead compound is present only in low quantity and/or technically it becomes very difficult to isolate such compound.[35] For any of intended utilise (drug, cosmetic, etc.,) of the compound, the required quantity may vary from few grams needed for preclinical drug development and safety studies in unlike setup; to quantities in kilogram required for clinical written report in dissimilar phases and many of tons of cosmetics.[4] And the availability of pb compound in such abundance tin be a key effect.

The limiting factors for the marine drug developments have been summarized in Table two. Lack of sustainable supply of the candidate compound has sometimes held back further research and development of many extremely potent marine novel compounds. Attempts have been made to shell this hurdle by increased development of synthetic or hemisynthetic analogues derivatives with desired and customized properties, or designing a pharmacophore of lower complexity with easier synthesis method.[36] Identification of a bioactive chemical compound synthesized or hemisynthesized must exist washed with the reference to the compound derived from the biological source. The structural complexity of the isolated chemical compound and meager yield which is mostly faced with marine compounds, may lead to wrong assignment of chemic formula of the compound, its real constitution (planar connectivity), configuration of intramolecular bonds, configuration entirity, and incorrectly assigned ane or multiple stereocenters.[37] To overcome the issue of regular supply, the utilize of natural resources should be nether control and need to favor the growth of marine organisms in its natural environment by farming which is also known every bit "Mariculture."[37,38] Another option is to culture the marine organisms under artificial conditions by the procedure called as "aquaculture" [Table 2].[37,38]

Table two

Limiting factors for the marine drug developments

Martins et al. has very well elucidated the commercial and marketplace issues that are relevant and mostly overlooked in the developmental process of new natural products.[four] Some of the points that need to exist addressed from the very early development phase are as follows: (i) What are the potential industrial apply of the product and need of that particular activity of the compound in the market? (ii) What will be the final cost per kg for the final bioactive fabric? (3) The desired conception and preferred road of administration of the compound; (four) What process of manufacture is being used and whether the supply is sustainable? and finally (v) How will the production reach the marketplace concatenation?

Some limitations of the marine drug development includes the development of universal expression systems for biosynthesis of small molecules with loftier-yield, development of genetic tools to access the in vivo potential of cultured marine microorganisms, and the regulatory arousing of silent biosynthetic pathways for small molecule discovery.[38]

The subsequent levels of evolution of drugs comprises in vivo evaluations of safe and efficacy in brute models, determination of the mechanism and site of action, development of structure-activeness relationships, formulation and characterization of pharmacokinetics parameters and pharmaceutical properties including improvements through the utilize of medicinal chemical science.[38]

Initial efforts in marine natural products chemistry have largely focused on collecting metabolites from most hands collected species.[30] Small-scale metabolites present in very pocket-sized quantities are a challenge for analytical and biological evaluations. In silico screening programs can be useful to understand the natural scaffolding of these small drug candidates better.[xxx] Scientists are making efforts to ameliorate the access to pocket-size metabolites through technological advancements, such as increasingly widespread utilise of NMR microcryogenic and capillary menstruation-probes, biological assays in increasingly smaller volumes such as in 384- and 1534-well plate formats and enhancements of the methods besides as information science and logistics associated with mass spectrometry.[39] Another area of improvement in marine drug discovery programs is the biological analysis methods of extracts, fractions, and pure compounds. Assay-based isolation design for marine natural products has the potential for automation that may outcome in dramatic comeback in the way past which different classes of natural products are discovered in nature.[38]

Looking at the vast potential and leads, there are several Institutes in India as well as all over the world, concentrating on research and training in marine pharmacology field. Nearly of the research institutes are concentrating on the discovery of potential novel compounds from marine organisms, extraction/isolation, their rubber and efficacy assessment and big-calibration commercial production. Some of the institutes doing research and universities imparting training on marine pharmacology in and [Tables ​ 3 and ​ 4] outside India are mentioned in respectively.

Table 3

Institutes/universities offer preparation or research on marine drugs in India

Table 4

Institutes/Universities offer training/inquiry on marine drugs outside India

Conclusions

Marine environment has become a promising source of natural products, molecules, and drugs of therapeutic use. Having enormous varieties with a great diversity of organism and virgin areas of marine life, the prospects of yielding more novel products from the sea is enormous. The curiosity of science and industry has established the oceans equally a prospective source for new potential drug leads. Scientists have come up with drugs of various categories out of which anticancer, anti-inflammatory, analgesics, and antivirals are the most important to mention. These lead molecules are in unlike stages of preclinical and clinical testing stages around the world. Many drugs from marine sources have a promising consequence on several chronic and unbeatable diseases similar cancer. They may testify to open upwards a new chapter of making the treatment of chronic diseases cheaper and successful.

Afterwards identification, extraction, and big scale product of promising marine natural products of therapeutic uses, their marketing and commercial exploitation of potential is dependent on the results of preclinical and clinical information. The current screening for active natural products should exist increased along with a large and rapid random screening method. Several research institutes and universities are working in this field to develop new moieties and train people to work in this area. The technology should exist targeted optimally for drug inquiry, approvals, and launches. The medical pharmacologist from Republic of india should consider taking up the further research in marine pharmacology to help our land in new drug developments. The importance of Marine Pharmacology is summarized in Figure one. The development of marine pharmacology equally a specialty in India volition aid united states optimizing the use of rich marine resources around our beautiful country gifted with a vast coastline [Figure 1].

Scope of marine pharmacology

Financial back up and sponsorship

Nil.

Conflicts of involvement

There are no conflicts of interest.

Acknowledgment

Author admit the support received from Dr. Namrata Singh for reviewing and editing the manuscript.

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Articles from Journal of Chemist's & Bioallied Sciences are provided hither courtesy of Wolters Kluwer -- Medknow Publications

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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4832911/

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