A Phytopharmacological Potential Of Marine DrugsName: Sneha Sharad Wakchaure Roll No: 66 Class: T. Y. B. Pharmacy Guided by: Ms. Rani Deshmukh

CONTENT Aim & Objectives Introduction Classification Of Marine Sources

Marine Sources & their Metabolites Types of Marine Drugs Therapeutic Uses Summary References

AIM & OBJECTIVES The main aim of review is to study, A phytopharmacological potential of marine drugs

The objective of review is to study, Marine drugs Sources of marine drugs. Types of marine drugs. Therapeutic importance of marine drugs.

INTRODUCTION Marine DrugsThese drugs are obtained from marine natural sources like marine plant, marine animal & marine microbes which is mainly useful to treat different major diseases.

Types of marine DrugsFrom Marine Plant 1. Dolastatin-10 2. ILX651 3. Cemadotin 4. Aplidin From Marine Animal 1. Ara-A 2. Ara-C 3. Conotoxins 4. LFA389 5. Bryostatin 6. Discodermolide 7. HTI286 8. Squalaminelactate 9. IPL512602(Seroid) From Marine Organism 1. Cphalosporins 2. Lyngbyatoxin 3. Debromoaplysiatoxin 4. Anatoxin-a 5.Vitamins of B complex 6. Vitamin-E 7. Fusaperazines A & B 8. Chalcomycin-B 9. Curacin-A

Classification of Marine SourcesAlgae Sea Slug Shark Cone Snail Actinomycete Lymgbya Majuscula

SeaweedsRhodophyta Phaeophyta Chlorophyta Zosteramarina

BryozoanSponge Mollusc Ascidians Corals Tunicates

CyanobacteriaPenicilium glabra

Marine sources & their Metabolites

Metabolites from Marine Sponges:

Approximately 10,000 sponges have been described in the world and most of them live in marine waters. A range of bioactive metabolites has been found in about 11 sponge genera. It has powerful anti-cancer, anti-inflammatory activities. Metabolites from Corals:

Prostaglandin in corals in the late 1960s contributed greatly to the rapid developments in the field of marine natural products. Palytoxin, which is one of the most potent known toxins, is the product of Palythoa species of the family Zoanthidae. It has mainly anti-cancer & anti-bacterial activities. Metabolites from Mollusc:

The first synthesis of siphonarin-B has confirmed the absolute stereochemistry of the metabolite isolated from the molluscs Siphonaria zelandica and S. atra. It has anti-analgesic & anticancer , antifungal, antimicrobial activities.

Metabolites from Ascidians:

This class of cyclic peptides provides important structural lead for a variety of antiviral, anticancer and immunosuppressant activities. & also inhibitory activity of matrix metalloproteinase (MMP2) from an ascidians of the family Polyclinidae. Metabolites from Microorganism: Many new sources of drug and many new families of antibiotics are found from these micro-organism.

Metabolites from Marine Bacteria: Over 10,000 of these are reported to have biological activity and over 100 microbial products are in use today as antibiotics, anti tumour agents, and agrochemicals.

Metabolites from Marine Fungi:

It is a rich and promising source of novel anticancer, antibacterial, antiplasmodial, anti-inflammatory and antiviral agents.

Metabolites from Marine Viruses: It has become increasingly clear that they play critical roles in the worlds oceans. the bioactive potential of marine viruses but the focus is turning these days to discover newer marine viruses and to study their physiological processes and the secondary metabolites produced. Metabolites from Micro Algae: Cyanobacteria are a diverse group of Gramnegative bacteria, also known as blue-green algae it has potent antimalarial, antitumour, and multidrug reversing activities.

Metabolites from Marine red Algae:

Carpopeltis affinis is a source of fusaperazines Aand B, the red alga Sphaerococcus coronopifolius was shown to have antibacterial activity.

Metabolites from Marine green Algae: The green alga Ulva lactuca was shown to posses an anti-inflammatory compound; and an anti-tumor compound was isolated from Portieria hornemannii. Ulva fasciata produces a novel sphingosine derivative has been found to have antiviral activity in vivo.

Therapeutic uses of marine drugs:1) Antibacterial activity 2) Antimicrobial activity 3) Antioxidant activity 4) Antiviral activity 5) Anti-infective activity 6) Inhibitory activity 7) Anti-malarial activity 8) Anti HIV activity 9) Antianalgesic activity 10) Anti-photoaging activity 11) Anti- inflammatory activity 12) Anti-Alzheimers activity 13) Anti fungal activity 14) Anti platelet activity 15) Antipsoriatic activity 16) Anti asthmatic activity 17) Anti coagulant activity 18) Immunosuppresive activity 19) Anti tuberculosis activity 20) Anti-proliferative activity 21) Chemopreventive activity

22) Anticancer activity:A) Respiratory cancer: a) Lung cancer b) Larynx Cancer c) Pharynx Cancer d) Oral Cancer B) Blood cancer: a) Leukaemia b) Non-Hodgkins cancer C) Gastrointestinal cancer: a) Colon cancer b) Pancreatic cancer c) Colorectal cancer D) Genitourinary cancer: a) Prostate cancer b) Renal cancer E) Gyanecologic cancer: a) Breast cancer b) Overian cancer F) Bone cancer: a) Sarcoma cancer G) Eye Cancer: a) Melanoma cancer H) Brain cancer: a) Tumour cancer I) Endocrine cancer: a) Thyroid cancer b) Skin cancer

Summary: The field of Marine medicines has clearly advanced from its early stages of chemical exploration to a new era in which marine derived drugs have following activities 1)

2)3) 4) 5) 6)

7)8) 9) 10)

Antibacterial activity Antioxidant activity Antituberculosis activity Anticoagulant activity Antiinflammatory activity Immunosuppresive activity Antimalarial activity Anti HIV activity Antianalgesic activity Anticancer activity Over the next decade, we will see significant numbers of marine drugs being used in the treatment of cancer, others for intense pain and infectious diseases. There will be an expansion of these studies to focus on many therapeutic areas of growing human need.

1) Antibacterial activity Halogeneted metabolites shows antibacterial activity from Malaysian species of the red algal genus Laurencia against clinical bacteria Staphylococcus aureas, Staphylococcus species, Streptococcus pyrogenes, Salmonella species and Vibrio cholerae by isolation. 2) Antimicrobial activity Bioactive secondary metabolites are derived from marine sponge phylum Porifera and associated bacteria shows antimicrobial activity against infectious and parasitic diseases including bacteria, viral, and protozoan infections by isolation. 3) Antioxidant activity Three species of seaweeds such as Sargasum dentifolium, laurencia and jania corniculata shows antioxidant activity by free radical scavenging DPPH(1-diphenyl-2picrylhydrazyl)-decolorization method. 4) Antiviral activity The most important antiviral lead of marine origin reported thus far is nucleoside Ara-A isolated from sponge Tethya crypta shows antiviral activity against viral DNA polymerase and DNA synthesis of herpes, vaccinica and varicella zoster viruses. 5) Anti-infective activity Isolated Streptomyces species strains from Mediterranean sponges due to their secondary metabolite production shows anti-infective activities. Bioassay-guided isolation and purification yielded three previously known compounds namely, cyclic depsipeptide valinomycin, indolocarbazole alkaloid staurosporine and butenolide. These compounds exhibited novel anti-infective activities specifically against Leishmania majo and Trypanosoma brucei brucei

6) Inhibitory activity The methanol and methanol-chloroform (1:1) extracts of the freshly collected marine sponge Haliclona exigua shows inhibitory activity against amoeba species Entamoeba histolytica. 7) Anti-malarial activity A brown alga Lobophora variegata, shows anti-malarial activity against Giardia intestinalis, Entamoeba histolytica and Trichomonas vaginalis. the whole extract showed the highest activity against T. vaginalis 8) Anti HIV activity Cyanovirin-N is a protein derived from cultures of the cyanobacterium, (blue-green algae) shows anti HIV activity. 9) Antianalgesic activity One cone snail poison shows antianalgesic activity against chronic pain. it has become a potent new pain medicine. Olivera's experiments have shown that the snail toxin is 1,000 times more powerful than morphine in treating certain kinds of chronic pain. The snail-derived drug, named Prialt by the company (Elan Corporation, plc in Dublin, Ireland) that developed and markets it, jams up nerve transmission in the spinal cord and blocks certain pain signals from reaching the brain.

10) Anti-photoaging activity The alga Corallina pilulifera methanol (CPM) extract has been shown antiphotoaging effect against matrix metalloproteinases (MMPs), a key component in photoaging of the skin due to exposure to, appear to be increased by UV-irradiationassociated generation of reactive oxygen species (ROS). 11) Anti- inflammatory activity Everton Tenorio de Souza et al. reported that bisindole indole alkaloid was isolated from the lipid extract of seaweed Caulerpa racemosa shows anti-inflammatory activity. 12) Anti-Alzheimers activity Bryostatin is prepared from marine bryozoan which shows anti-alzheimers activity. It stimulates the production of proteins in cells that are essential for long-term memory. Early Alzheimer's patients typically cannot store new long-term memories. Studies in mice and that bryostatin can promote the proteins required to construct permanent memory and biochemically enhance precisely this storage of long-term memory. 13) Anti fungal activity The sesquiterpenoids (+)-curcuphenol and (+)-curcudiol isolated from the Caribbean sponge Didiscus oxeata shows antifungal activity against several filamentous fungi.

14) Anti platelet activity Out of 261 crude methanol extracts of marine sponge Xestospongia sp. yielded a xestospongin/araguspongine-type molecule shows antiplatelet aggregation activity. 15) Antipsoriatic activity Avarol is a marine sesquiterpenoid hydroquinone shows anti-inflammatory and antipsoriatic activity. The aim of this study was to evaluate the in vitro and in vivo pharmacological behaviour of the derivative avarol-3-thiosalicylate (TA) on some inflammatory parameters related to the pathogenesis of psoriasis. 16) Anti asthmatic activity The extracts of an edible red alga, Laurencia undulata ethanolic (EtOH) containing a large amount of polyphenols shows antiasthmatic activity against bronchial asthma associated with allergic diseases. 17) Anti coagulant activity The polysaccharides from marine algae show anticoagulant activity. These marine algal isolated and characterized that are biologically active compounds have shown anti-platelet and anticoagulant proteins and fibrinolytic enzymes. 18) Immunosuppresive activity Crude polysaccharide extracts were obtained from aqueous extracts of the microalgae Chlorella stigmatophora and Phaeodactylum tricornutum. The C. stigmatophora extract showed immunosuppressant activity.

19) Anti tuberculosis activity The structurally diverse marine-derived natural and semisynthetic compounds show antituberculosis activity against Mycobacterium tuberculosis. Three new classes of compounds including C-19 hydroxy steroids, scalarin sesquiterpenoids and tetrabromo spirocyclohexadienylisoxazolines have been identified. 20) Anti-proliferative activity The extract of mediterranean sponge, Spongia officinalis shows anti-inflammatory and antiproliferative activity against three human cancer cells. 21) Chemopreventive activity Polysaccharides from the starfish Asterina pectinifera show chemopreventive activity against cell proliferation in human breast carcinoma cell lines. 22) Anticancer activity A) Respiratory cancer a) Lung cancer Purified polysaccharide of Viva-Natural, from an edible seaweed extract shows anti lung cancer activity against intraperitoneally implanted Lewis lung carcinoma in syngeneic mice. b) Larynx Cancer Ziconitide, known by its trade name Prialt is a synthetic form of a compound extracted from the venom of predatory tropical cone snails Conus species shows anti larynx cancer activity. It also use in treatment for severe cases of chronic pain in patients with conditions such as cancer and AIDS. Current clinical results suggest that Prialt is a powerful, non-addictive alternative to drugs such as morphine.

c) Pharynx Cancer Many toxic marine macrolides shows anti cancer activity in tumour, pharynx cancer etc. These marine toxins can knock out the lynchpins in these long chains or cap their ends and kill cancer cells. d) Oral Cancer Eighty-four marine gliding bacteria were isolated which capable of producing the cytotoxic metabolites shows anticancer activity against selected human cell lines breast adenocarcinoma (MCF-7), colon cancer (HT-29), cervical cancer (HeLa) and oral cancer (KB). B) BLOOD CANCER a) Leukaemia The Aplidin isolated from marine tunicates Aplidium albicans shows anti leukamia cancer activity against on fresh leukaemia cells derived from children with B-cellprecursor (BCP), acute lymphoblastic leukaemia (ALL). b) Non-Hodgkins cancer Scallops are mollusks that have two beautiful convexly ridged or scalloped, shells which show anticancer activity against three types of cancer: leukaemia, multiple myeloma, and non-Hodgkin's lymphoma.

C) Gastrointestinal cancer a) Colon cancer The crude extracts of Brazilian marine sponges, ascidians, bryozoans and octocorals shows anticolon cancer activity against strains of susceptible and antibiotic-resistant bacteria, one yeast (Candida albicans), Mycobacterium tuberculosis, three cancer cell lines MCF-7 (breast), B16 (murine melanoma ) and HCT8 (colon), and Leishmania tarentolae adenine phosphoribosyl transferase (L-APRT) enzyme. Less than 15% of marine sponge crude extracts displayed antibacterial activity. More than 25% of ascidian crude extracts were active against M. tuberculosis and the three cancer cell lines. b) Pancreatic cancer The batzellines are pyrroloiminoquinones alkaloids obtained from the deep-water Caribbean sponge Batzella species (family Esperiopsidae, order Poecilosclerida) shows anticancer activity against pancreatic cancer cell lines. c) Colorectal cancer Scallops are molluscs that have two beautiful convexly ridged, or scalloped, shells. They consist of two shells hinged at one end. A diet rich in the omega-3 fats, which are found in scallops shows anti cancer activity against colorectal cancer. D) GENITOURINARY CANCER a) Prostate cancer Marine natural product and their synthetic derivatives makaluvamine compounds, and found that the most potent was BA-TPQ [(11,12),7-(benzylamino)-1,3,4,8tetrahydropyrrolo[4,3,2-de]quinolin-8(1H)-one] shows anticancer activity against human and murine prostate cancer cells.

b) Renal cacer Marine derived natural and semisynthetic compound sesquiterpenoid shows anticancer activity against renal cancer cell lines. E) GYNECOLOGIC CANCER a) Breast cancer Polysaccharides from the starfish Asterina pectinifera show anti cancer and chemopreventive activity against cell proliferation in human breast carcinoma cell lines. b) Overian cancer (Ecteinascidin-743) ET-743 isolated from the marine tunicate Ecteinascidia turbinata shows anticancer activity against soft tissue sarcoma, ovarian and breast cancer cells. F) BONE CANCER a) Sarcoma cancer Ecteinascidin-743 (ET-743), isolated from the marine tunicate Ecteinascidia turbinata shows anticancer activity against a panel of human osteosarcoma and Ewings sarcoma cell lines, bone tumor cells. G) EYE Cancer a) Melanoma cancer The crude extracts of Brazilian marine sponges, ascidians, bryozoans and octocorals shows activity against strains of susceptible and antibiotic-resistant bacteria, one yeast (Candida albicans), Mycobacterium tuberculosis, three cancer cell lines breast, murine melanoma and colon.

H) BRAIN CANCER a) Tumour cancer Two purified proteins G-6 and G-4-2 obtained from Arca subcrenata Lischke shows anti tumour cancer activity against cancer tumour cells. I) ENDOCRINE CANCER: a) Thyroid cancer Plitidepsin (Aplidine) is isolated from Aplidium albicans, a marine tunicate shows anticancer activity against medullary thyroid cancer (MTC). b) Skin cancer Sarcophine-diol (SD) is marine natural product isolated from soft coral sarcophyton glaucum and it structural modifications of sarcophine, has shown anticancer and chemopreventive activity against skin tumor development in female mice. The objective of this study was to determine the chemopreventive effects of SD on UVB induced skin tumor development in hairless SKH-1 mice, a model more relevant to human skin cancer.

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