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FOREWORD
PREFACE
Introduction
Abstract
Introduction
Role of Seas and Oceans in Human Life
Marine Biodiversity
Origin of Marine Drugs
Marine Organisms as Sources of Drugs
Need for the Production of Marine Drugs
Pharmaceutical Marine Biodiversity and Drug Development
Problems in the Development of New Marine Drugs
Remedial Measures for the Supply of Bioactive Compounds
Present Status of Marine Drug Discovery
Scope for Active Research on the Development of Marine Drugs
CONCLUSION
Marine Bioprospecting
Abstract
INTRODUCTION
Marine Ecosystems and their Pharmaceutical Biodiversity
Open Marine Ecosystem
Deep-Sea Ecosystem
Sandy Beach Ecosystem
Rocky Marine Ecosystem
Coral Reef Ecosystem
Kelp Forest Ecosystem
Estuarine Ecosystem
Saltwater Wetland Ecosystem
Mangrove Ecosystem
Polar Marine Ecosystem
Marine Bioactive Compounds
Therapeutic Activities of Marine Bioactive Compounds
Bioactive Compounds of Marine Organisms
Chemical Classes of Marine Bioactive Compounds
Potential Bioactive Compounds of Different Constituents of Marine Life
Bioactivity-based Contribution of Marine Bioactive Compounds
Status of Isolated Marine Bioactive Compounds
Marine Bioactive Compounds as Diagnostics and Experimental Tools
Enzymes
Green Fluorescent Protein (GFP) and Phycoerythrin
Okadaic Acid
Palytoxin
Limulus-Amoebocyte-Lysate (LAL)
Keyhole Limpet Hemocyanin (KLH)
Tetrodotoxin
Marine Biopharmaceuticals
Advantages of Biopharmaceuticals
Generics vs Biosimilars
Bio-betters
Development of Marine Biopharmaceuticals (Development of Marine Drugs)
Green Processing Methods to Extract Biomolecules from Marine Life
Traditional Methods
Modern Methods
Fermentative Extraction
Enzymatic Extraction
Supercritical Fluid Extraction
Pressurized Liquid Extraction
Subcritical Water Extraction
Supercritical CO2 Extraction
Pressurized Hot Water Extraction
Pulse Electric Field-Assisted Method
Microwave-Assisted Method
Ultrasound-Assisted Method
High Hydrostatic Pressure
Extrusion-assisted Extraction
Membrane Separation Technologies
Combined Extraction Techniques
Major Problems in the Development of New Marine Pharmaceuticals (= Marine Drugs)
How to Address the Supply Problem?
Aquaculture
Genetic Engineering
Synthesis/Semi Synthesis/Modification
Remedial Measures for the Supply of Bioactive Compounds
Conclusion
Promising Pharmaceutical Compounds of Marine Plants: Their Chemistry and Therapeutic Applications
Abstract
INTRODUCTION
SEAWEEDS
Pharmaceutically Most Important Seaweed Species
Green Algae
Brown Algae
Red Algae
THE BIOACTIVE COMPOUNDS AND THEIR THERAPEUTIC ACTIVITIES OF SEAWEEDS
Anticancer Activity
Green Algae
Bryopsis sp.
Caulerpa racemosa var. cylindracea
Caulerpa racemosa and Caulerpa scalpelliformis
Codium decorticatum
Ulva lactuca and Ulva fasciata
Ulva rigida
Brown Algae
Fucus vesiculosus, Alaria esculenta, Ascophyllum nodosum, Laminaria japonica, Sargassum muticum and Bifurcaria bifurcata
Carpodesmia tamariscifolia (= Cystoseira tamariscifolia)
Colpomenia sinuosa and Sargassum prismaticum
Eisenia bicyclis
Ecklonia cava
Fucus vesiculosus
Ishige okamurae
Laminaria digitata
Laminaria japonica
Sargassum carpophyllum
Sargassum hemiphyllum
Sargassum sp.
Stypodium zonale
Undaria pinnatifida
Unidentified species of brown Algae
Red Algae
Champia parvula
Chondrus armatus
Chondrus ocellatus
Chondrus, Gigartina, Eucheuma and Iridaea spp
Gigartina pistillata
Gracilaria dominguensis
Grateloupia filicina
Portieria hornemannii
Spyridia fusiformis
Anticancer Compounds from Seaweeds that are Already in Use or in Advanced Clinical Trials
Antiviral Activity
Green Algae
Caulerpa brachypus
Caulerpa sp.
Ulva fasciata
Ulva lactuca
Brown Algae
Fucus evanescens
Sargassum patens
Red Algae
Gigartina skottsbergii
Laurencia obtusa and Pterocladia capillacea
Schizymenia binderi
Anti-inflammatory Activity
Green Algae
Caulerpa mexicana
Caulerpa racemosa
Chaetomorpha linum, Ulva intestinalis, Ulva lactuca and Ulva prolifera
Codium decorticatum
Ulva conglobata
Brown Algae
Fucus vesiculosus
Rhizoclonium riparium
Antioxidant Activity
Brown Algae
Colpomenia sinuosa and Sargassum prismaticum
Cystoseira hakodatensis and Sargassum horneri
Cystoseira sedoides, Cladostephus spongeosis and Padina pavonica
Red Algae
Laurencia dendroidea
Anticoagulant Activity
Brown Algae
Fucus vesiculosus
Undaria pinnatifida
Red Algae
Solieria filiformis
Antidiabetic Activity (Alpha-glucosidase Inhibitory Activity and the Anti-hyperglycemic Effects)
Brown Algae
Ecklonia cava
Ecklonia stolonifera
Ishige okamurae
Macrocystis pyrifera and Sargassum fusiforme
Undaria pinnatifida
Red Algae
Grateloupia lithophila, Spyridia filamentosa, Grateloupia lithophila and Hypnea musciformis
Hypnea valentiae
Laurencia dendroidea
Anti-allergic Effects
Ecklonia stolonifera
AChE and BChE Inhibitory Activity (for the Treatment of Alzheimer's Disease)
Brown Algae
Brown and Red Algae
Angiotensin-converting Enzyme (ACE) Inhibitory Activity (Angiotensin Receptor Blockers for Treating Cardiovascular Disorders)
Brown Algae
Ecklonia cava
Ecklonia stolonifera
Antiaging Activity
Cystoseira nodicaulis, Eisenia bicyclis and Ecklonia kurome
Ecklonia cava
Anti-obesity Activity (Anti-adipogenesis)
Brown Algae
Ecklonia cava
Ecklonia stolonifera
Eisenia bicyclis
Ishige okamurae
Red Algae
Gracilaria lemaneiformis, Kappaphycus alvarezii and Sarconema filiforme
Antinociceptive Activity
Dichotomaria obtusata
Neuroprotective Activity
Hepatoprotective Activity
Brown Algae
Colpomenia sinuosa and Sargassum prismaticum
Turbinaria ornata
Red Algae
Gracilaria crassa and Laurencia papillosa
Antiulcer Activity
Gracilaria crassa and Laurencia papillosa
Wound Healing Activity
Brown Alga
Turbinaria ornata
Red Algae
Gracilaria crassa and Laurencia papillosa
Immunomodulatory Activity
Green Alga
Ulva conglobata
Brown Algae
Undaria pinnatifida, Laminaria japonica, Laminaria cichorioides, Fucus vesiculosus and Fucus evanescens
Ascophyllum nodosum, Macrocystis pyrifera, Undaria pinnatifida, and Fucus vesiculosus
Red Alga
Gracilaria fisheri
SEAGRASSES
Biomedically Important Seagrass Families and their Species
Cymodoceaceae
Hydrocharitaceae
Posidoniaceae
Zosteraceae
Bioactive Compounds of Seagrasses and their Therapeutic Activities
Bioactivities of the Sea Grass Extracts
Anti-Inflammatory Activity
Posidonia oceanica
Syringodium filiforme and Thalassia testudinum
Halophila ovalis
Thalassodendron ciliatum
Antiviral Activity
Posidonia oceanica
Thalassodendron ciliatum
Thalassia hemprichii
Unidentified species of Zosteraceae family
Anti-Dengue Activity (Larvicidal Activity)
Cymodocea serrulata
Enhalus acoroides
Halophila ovalis
Halodule pinifolia
Syringodium isoetifolium
Thalassia hemprichii
Thalassia testudinum
Lipid-Reducing Activity
Thalassia hemprichii
Halophila stipulacea
Anti-diabetic Activity
Syringodium filiforme and Thalassia testudinum
Halophila stipulacea
Thalassia hemprichii
Halophila beccarii
Halodule uninervis
Posidonia oceanica
Hepatoprotective Activity
Thalassia hemprichii
Halodule uninervis
Cymodocea rotundata
Thalassodendron ciliatum
Anti-Aging Activity
Posidonia oceanica
MANGROVES
Pharmaceutically Important Species of Mangroves
Pharmaceutical Importance of True Mangroves
THE BIOACTIVE COMPOUNDS OF MANGROVES AND THEIR THERAPEUTIC ACTIVITIES
Anticancer Activity
Aegiceras corniculatum
Avicennia alba
Bruguiera gymnorrhiza
Excoecaria agallocha
Heritiera littoralis
Rhizophora stylosa
Sonneratia paracaseolaris
Xylocarpus granatum
Xylocarpus spp
Ceriops tagal
Bruguiera cylindrica
Anti-inflammatory and Antioxidant Activities
Avicennia marina
Bruguiera gymnorhiza
Excoecaria agallocha
Kandella candel
Rhizophora mucronata
Rhizophora annamalayana
Xylocarpus granatum
Xylocarpus moluccensis
Antiviral Activity
Sonneratia paracaseolaris
Rhizophora mucronata
Antiulcerogenic Activity
Xylocarpus moluccensis
Halophytes
Salicornia ambigua (=Sarcocornia ambigua)
Salicornia europaea (=Salicornia herbacea)
Salicornia freitagii
Salicornia patula
CONCLUSION
Promising Pharmaceutical Compounds of Marine Sponges: Their Chemistry and Therapeutic Applications
Abstract
INTRODUCTION
Marine Sponge Species Yielding Promising Bioactive Compounds
Anticancer Activity
Leucetta chagosensis
Leucetta microraphi
Agelas mauritiana
Axinella brevistyla
Axinella infundibuliformis
Cymbastela cantharella
Lithoplocamia lithistoides
Lipastrotethya sp.
Chondrosia corticata
Spirastrella pachyspira
Aplysilla glacialis
Candidaspongia sp.
Dysidea etheria
Ircinia ramosa
Ircinia sp.
Psammocinia sp.
Sarcotragus sp. 1
Sarcotragus sp. 2
Coscinoderma mathewsi
Spongia sp. 1
Spongia sp. 2
Cacospongia mycofijiensis
Dactylospongia elegans
Dactylospongia metachromia, (= Hippospongia metachromia)
Fascaplysinopsis reticulata
Fascaplysinopsis sp. 1
Fascaplysinopsis sp. 2
Fasciospongia cavernosa
Hyrtios erectus
Hyrtios reticulatus
Hyrtios sp.
Lendenfeldia chondrodes (= Fasciospongia chondrodes)
Scalarispongia scalaris (= Cacospongia scalaris)
Smenospongia aurea
Arenosclera brasiliensis
Callyspongia (Callyspongia) siphonella (= Siphonochalina siphonella)
Callyspongia sp.
Siphonochalina sp.
Haliclona (soestella) mucosa
Haliclona sp.
Haliclona (Reniera) sp. (= Prianos sp.)
Niphates olemda
Pachychalina alcaloidifera
Neopetrosia chaliniformis (= Xestospongia exigua)
Petrosia sp.
Xestospongia sp.
Oceanapia incrustata (= Rhizochalina incrustata)
Oceanapia sagittaria
Batzella sp.
Forcepia sp.
Crambe crambe
Crambe tailliezi
Monanchora arbuscula
Monanchora pulchra
Monanchora unguiculata
Kirkpatrickia variolosa
Latrunculia (latrunculia) brevis
Mycale hentscheli
Mycale sp.
Diacarnus megaspinorhabdosa
Negombata magnifica
Stylissa flabeliformis
Stylissa massa (= Hymeniacidon aldis)
Stylissa sp.
Halichondria (halichondria) okadai
Aaptos aaptos
Aaptos suberitoides
Aaptos sp.
Hemiasterella vasiformis var., minor (= Hemiasterella minor)
Tectitethya crypta (= Cryptotheca crypta)
Jaspis stellifera
Jaspis sp.
Rhabdastrella globostellata
Stelletta sp.
Leiodermatium sp.
Pachastrissa sp.
Geodia japonica
Geodia tylastra (= Geodia corticostylifera)
Pachymatisma johnstonia
Amphibleptula sp.
Discodermia calyx
Discodermia dissoluta
Trachycladus spinispirulifera (= spirastrella spinispirulifera)
Aplysina aerophoba
Ianthella sp.
Pseudoceratina purpurea (= Dendrilla verongiformis)
Pseudocerarina sp. (= Psammaplysilla sp.) 1
Pseudoceratina sp. (= Psammaplysilla sp.) 2
Aphrocallistes beatrix
Plakinastrella sp.
Plakortis angulospiculatus
Plakortis halichondrioides
Antiviral Activity
Agelas flabelliformis
Agelas oroides
Axinella cf. corrugaata
Paratimea sp. (= Halicortex sp.)
Dendrilla membranosa
Dysidea avara and Dysidea cinerea
Dysidea sp.
Hippospongia metachromia
Cacospongia mycofijiensis
Hyrtios sp.
Haliclona sp.
Acanthostrongylophora sp.
Neopetrosia contignata (= Petrosia contignata)
Pachypellina sp.
Desmapsamma anchorata
Hamigera tarangaensis
Phorbas sp.
Mycale sp. 1
Mycale sp. 2
Stylissa carteri
Halichondria (Halichondria) semitubulosa (= Pellina semitubulosa)
Hymeniacidon sp.
Aaptos sp.
Tectitethya crypta (= Tethya crypta)
Stelletta clavosa
Stelletta sp.
Erylus goffrilleri
Geodia microspinosa (= Sidonops microspinosa)
Siliquariaspongia mirabilis
Theonella mirabilis and Theonella swinhoei
Ianthella quadrangulata
Antimalarial Activity
Agelas gracilis
Agelas mauritiana
Agelas oroides
Agelas sp.
Pipestela hooperi (= Cymbastela hooperi)
Biemna laboutei
Acanthella sp.
Coscinoderma sp.
Hyattella sp.
Fascaplysinopsis reticulata
Hyrtios erectus
Haliclona sp.
Acanthostrongylophora ingens
Xestospongia sp. 1
Xestospongia sp. 2
Zyzzya sp.
Diacarnus levii
Diacarnus erythraeanus
Diacarnus megaspinorhabdosa
Tedania (Tedania) brasiliensis
Axinyssa djiferi
Hymeniacidon sp.
Spongosorites sp.
Penares nux (= Pachastrissa nux)
Aplysinella strongylata
Verongula sp.
Pseudoceratina purpurea
Pseudoceratina sp.
Plakinastrella sp.
Plakortis simplex
Plakortis halichondrioides
Plakortis lita
Plakortis simplex
Antidiabetic activity
Agelas mauritianus
Agelas oroides
Axinella cannabina
Axinella polypoides
Dictyonella incisa
Cliona viridis
Dysidea avara
Dysidea villosa
Dysidea sp.
Lamellodysidea herbacea
Ircinia dendroides
Ircinia incisa
Ircinia oros
Ircinia variabilis
Sarcotragus spinulosa
Hippospongia lachne
Spongia sp. (= Euryspongia sp.)
Callyspongia truncata
Petrosia (petrosia) ficiformis
Xestospongia muta
Siphonodictyon coralliphagum (= Aka coralliphaga)
Hemimycale arabica
Mycale sp.
Aplysina aerophoba
Antitubercular Activity
Agelas sp.
Hyrtios aeticulatus
Arenosclera brasiliensis
Callyspongia (cladochalina) aerizusa
Haliclona sp.
Acanthostrongylophora sp.
Halichondria (halichondria) panicea
Jaspis splendens
Corticium sp.
Antiparasitic Activity
Agelas sp.
Chondrosia reniformes
Dysidea avara
Sargotragus spinosulus (= Ircinia spinosula
Sarcotragus sp.
Amphimedon viridis
Monanchora arbuscula
Crella (crella) sp.
Pandaros acanthifolium
Mycale (Zygomycale) angulosa (= Mycale angulosa)
Negombata corticata
Petrosid Ng5 Sp5
Tethya ignis
Tethya rubra
Cardiotropic (Anti-cardiovascular) Activity
Lamellodysidea chlorea
Halichondria (Halichondria) okadai
Eryltus formosus
Theonella swinhoei
Theonella sp.
CONCLUSION
Promising Pharmaceutical Compounds of Marine Cnidarians: Their Chemistry and Therapeutic Applications
Abstract
INTRODUCTION
Hydroids (Hydrozoa)
Biopharmaceutically Important Marine Hydrozoans
Anticancer Marine Hydrozoans
Class: Scyphozoa
Pharmaceutically Important Marine Scyphozoan medusae
Therapeutic Activities of Marine Scyphozoan medusae
Atolla vanhoeffeni
Aurelia aurita
Aurelia coerulea
Nemopilema nomurai
Class: Anthozoa
Scleractinian Corals and Sea Anemones (Subclass: Hexacorallia)
Pharmaceutically Important Marine Scleractinian Corals and Sea Anemones
Promising Secondary Metabolites of Sea Anemones and Scleractinian Corals and their Bioactivities
Soft corals (Subclass: Octocorallia; Order: Octocorallia (Formerly Orders, Alcyonacea and Gorgonacea)
Pharmaceutically Important Marine Soft Corals
Promising Secondary Metabolites of Soft Corals and their Bioactivities
Capnella imbricata
Dendronephthya rubeola
Nephthea chabroli
Nephthea erecta
Xenia novaebrittanniae
Xenia plicata (= Xenia blumi)
Sarcophyton crassocaule
Lobophytum cristagalli
Lobophytum durum and Lobophytum crassum
Lobophytum spp.
Klyxum simplex
Sinularia sp.
Sinularia gibberosa and Sinularia querciformis
Sinularia spp.
Paralemnalia thyrsoides
Clavularia viridis
Clavularia koellikeri
Clavularia spp.
Cespitularia hypotentaculata
Asterospicularia laurae
Telesto riisei
Isis hippuris
Pseudopterogorgia bipinnata
Pseudopterogorgia spp.
Eunicea fusca
Junceella fragilis
Briareum excavata
Briareum asbestinum (= Briareum polyanthes)
CONCLUSION
Promising Pharmaceutical Compounds of Marine Bryozoans: Their Chemistry and Therapeutic Applications
Abstract
INTRODUCTION
Marine bryozoans with promising bioactive compounds
Anticancer and Cytotoxic Activities of Marine Bryozoans
Alkaloids
Dibrominated alkaloids
Bromopyrrole alkaloids
Brominated alkaloids
β-Carboline alkaloids
Caulamidines
Caulibugulones
Convolutamides
Convolutamydines
Convolutamines
Eusynstyelamides
Perfragilins
Polycyclic indole alkaloids
Pterocellins
Tambjamines
Terminoflustrindoles
Lactones
Bryostatins
Bryostatin-1
Bryostatin-5
Bryostatin-8
Bryostatin-19
Bryostatin Analogues (Bryostatins (1, 2, 3, 7, 9, and 16))
Neristatin 1
Myriaporones
Other Lactones
Ceramides
Sterols
Other Anticancer and Cytotoxic Compounds
Antiviral Activity
Antiparasitic Activity
Antiprotozoal (Antitrypanosomal) Activity
Anthelmintic (Nematocidal) Activity
Antimalarial (Anti-plasmodial) Activity
Antiangiogenic Activity
Topoisomerase Inhibitory Activity
Metalloprotease Collagenase IV Inhibitory Activity
Anti-Alzheimer’s Activity
Antiparkinson Activity
Anti-Post-stroke Activity
CONCLUSION
Promising Pharmaceutical Compounds of Marine Worms: Their Chemistry and Therapeutic Applications
Abstract
INTRODUCTION
Marine Nemertine Worms
Pharmaceutically Important Species of Marine Nemertine Worms: Amphiporus lactifloreus and Notospermus geniculatus
Bioactivities of Marine Nemertine Worms
Amphiporus lactifloreus
Anti-Alzheimer’s Activity
Notospermus geniculatus
Bioactivities
Sipunculids
Pharmaceutically Important Species of Sipunculids: Phascolosoma esculenta, Phascolosoma sp. and Sipunculus (Sipunculus) nudus
Bioactivities of Promising Polysaccharides and Peptides of Peanut Worms, Phascolosoma esculenta and Sipunculus nudus
Anti-cancer Activity of Polysaccharides
Sipunculus nudus
Anti-oxidant Activity of Polysaccharides
Phascolosoma esculenta
Sipunculus nudus
Anti-inflammatory Activity of Polysaccharides
Phascolosoma esculenta
Sipunculus nudus
Anti-hypoxia Activity of Polysaccharides
Sipunculus nudus
Immunomodulatory Activity of Polysaccharides
Phascolosoma esculenta
Sipunculus nudus
Anti-oxidant Activity of Peptides
Phascolosoma esculenta
Sipunculus nudus
Anti-inflammatory Activity of Peptides
Sipunculus nudus
ACE-inhibitory/Anti-hypertensive Activity of Peptides
Phascolosoma esculenta
Sipunculus nudus
Effects of Peptides on Wound Healing and Spatial Learning and Memory
Phascolosoma esculenta
Sipunculus nudus
Marine Annelids
Pharmaceutically Important Species of Marine Annelids: Arenicola marina and Hermodice carunculata
Bioactive Compounds of Marine Annelids
Arenicola marina
Hermodice carunculata
CONCLUSION
Promising Pharmaceutical Compounds of Marine Shellfish: Their Chemistry and Therapeutic Applications
Abstract
INTRODUCTION
Marine Crustaceans
Pharmaceutically Important Shrimps, Prawns and Crabs
Shrimps and Prawns
Crabs
Major Bioactive Compound of Marine Crustaceans
Bioactivities of Marine Crustaceans
Anticancer, Antiproliferative and Cytotoxic Activity
Anti-inflammatory Activities
Antioxidant Activity
Antidiabetic Activity
Hepatoprotective Activity
Anti-aging Activity
Eye Health and Vision
Marine Molluscs
Pharmaceutically Important Marine Bivalves
Therapeutic Activities in Marine Bivalves
Pharmaceutically Important Marine Gastropods
Secondary Metabolites of Marine Gastropods and their Bioactivities
Pharmaceutically Important Cephalopods
Therapeutic Values of Cephalopods
Dosidicus gigas
Uroteuthis (Photololigo) duvaucelii (= Loligo duvaucelii)
Loligo vulgaris
Octopus vulgaris
Therapeutic Values of the Ink of Cephalopods, Sepiella inermis and Loligo duvauceli
Anticancer Activity
Anti-inflammatory Activity
Antioxidant Activity
Anti-hypertensive Activity
Anti-retroviral Activity
Anti-ulcerogenic Activity
Hematopoietic Effects
Echinoderms
Biopharmaceutically Important Sea Stars and Starfish (Class: Asteroidea)
Biopharmaceutically Important Brittle Stars (Class: Ophiuroidea)
Biopharmaceutically Important Sea Urchins (Class: Echinoidea)
Other Bioactivities of Sea Urchins
Arbacia lixula
Diadema savignyi
Echinometra mathaei
Mesocentrotus nudus
Paracentrotus lividus
Scaphechinus mirabilis
Strongylocentrotus franciscanus Lytechinus variegatus, and Echinometra lucunter
Strongylocentrotus nudus
Strongylocentrotus purpuratus
Toxopneustes pileolus
Tripneustes gratilla
Biopharmaceutically Important Crinoids (Class: Crinoidea)
Biopharmaceutically Important Crinoid Species
Biopharmaceutical Compounds of Crinoids and their Therapeutic Activities
Capillaster multiradiatus
Comantheria rotula
Comanthus parvicirrus
Comanthus sp.
Comatula rotalaria
Dichrometra flagellata
Biopharmaceutically Important Sea Cucumbers (Class: Holothuroidea)
OTHER PROMISING COMPOUNDS OF SEA CUCUMBERS AND THEIR THERAPEUTIC USES
Antihyperglycemic Effects
For Treating Insulin Resistance
Antidiabetic Activity
Cucumaria frondosa
Holothuria leucospilota
Thelenota ananas and Cucumaria frondosa
Anticoagulant Activity
Antihyperlipidemic (Dyslipidemic) Activity
Acaudina molpadioides and Isostichopus badionotus
Apostichopus japonicus and Holothuria leucospilota
Cucumaria frondosa
Apostichopus japonicus and Holothuria leucospilota
Isostichopus badionotus and Pearsonothuria graeffei
Pearsonothuria graeffei
Wound and Bone Healing
Stichopus herrmanni
Stichopus japonicus
Acaudina leucoprocta
Apostichopus japonicus
Colochirus quadrangularis
Holothuria poli and Holothuria tubulosa
Neurological Diseases
Acaudina molpadioides
Cucumaria frondosa
Holothuria fuscopunctata
Thelenota ananas and Holothuria fuscopunctata
Thelenota ananas
Pearsonothuria graeffei
Holothuria poli
Ageing and Memory Impairments
Apostichopus japonicus
Cucumaria frondosa
Holothuria leucospilota
Stichopus japonicus
CONCLUSION
Promising Pharmaceutical Compounds of Marine Tunicates: Their Chemistry and Therapeutic Applications
Abstract
INTRODUCTION
Biopharmaceutically Important Ascidians
CONCLUSION
Promising Pharmaceutical Compounds of Marine Fishes: Their Chemistry and Therapeutic Applications
Abstract
INTRODUCTION
Pharmaceutically Important Bony Fishes
BIOPHARMACEUTICALS FROM MARINE FISHES
Bony Fishes (Class: Osteichthyes)
Anguilla japonica
Cynoglossu semilaevis
Epinephelus coioides
Anticancer Activity
Antiviral Activity
Antibacterial Activity
Antifungal Activity
Immunomodulatory Effects
Wound Healing Property
Hippoglossus hippoglossus
Lagocephalus scleratus
Lateolabrax japonicus
Limanda aspera
Miichthys miiuy
Pagrus major
Pardachirus marmoratus
Pleuronectes platessa
Pseudopleuronectes americanus
Sarda orientalis
Seriola lalandi
Tachysurus fulvidraco
Pharmaceutically Important Cartilaginous Fish (Class: Chondrichthyes)
Squalus acanthias
Anticancer Activity
Antiviral Activity
Pharmaceutically Important Jawless Fish (Class: Agnatha)
Myxine glutinosa
CONCLUSION
Marine Biopharmaceutical Compounds against SARS-CoV-2
Abstract
INTRODUCTION
POTENTIAL MARINE BIOTA FOR THE PREVENTION/TREATMENT OF SARS-COV-2 VARIANTS
Seaweeds
Dictyosphaeria versluyii
Dictyota pfaffii
Ecklonia cava
Saccharina japonica
Sargassum spinuligerum
Sargassum wightii
Sargassum sp.
Corallina officinalis
Chondrus crispus and Euchema cottonii
Marine Sponges
Agelas oroides
Axinella cf. corrugata
Axinellae polypoides
Petrosia strongylophora
Plakortis halichondroides
Theonella spp.
Soft Corals
Briareum sp.
Pterogorgia citrina
Conclusion
Marine Biopharmaceuticals in Pipeline
Abstract
INTRODUCTION
APPROVED AND MARKETED MARINE BIOTA - DERIVED DRUGS
Approved Drugs
Marine Biota-derived Drug Candidates Under Clinical Trials
Marine Biota -derived Drug Candidates Under Clinical Trials up to 2021
Marine Drug Candidates Under III Phase Clinical Trials
Marine Drug Candidates Under II Phase Clinical Trials
Marine Drug Candidates Under I Phase Clinical Trials
Marine Biota-derived Clinical Level Compounds against SARS-CoV-2
CONCLUSION
New PG Degree Course, Marine Bio-Pharmacy: Scope and Career Prospects
Abstract
INTRODUCTION
Marine Biopharmaceuticals
Marine Bio-Pharmacy (=Marine Biopharmaceutical Sciences or Pharmaceutical Marine Biology, an Interdisciplinary PG Course)
Suggested Syllabus for the Master's Degree Program in “Marine Bio-Pharmacy (Marine Biopharmaceutical Sciences)”
Taught Program
Practicals
Pharmaceutical Marine Biology, an Interdisciplinary Course
Syllabus for the Taught Program
Suggested Practicals
Career Opportunities for the Marine Bio-Pharmacy Graduates
CONCLUSION
REFERENCES
Marine Biopharmaceuticals: Scope and Prospects
Authored bySanthanam RameshKaruna College of Pharmacy
Kerala University of Health Sciences, Palakkad
Kerala, India
Ramasamy SanthanamFisheries College and Research Institute
Tamil Nadu Veterinary and Animal Sciences University
Thoothukudi, India
&
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FOREWORD
I am delighted to write this foreword, not only because Prof. Ramasamy Santhanam, one of the authors, has been my teacher and colleague for more than 30 years, but also because I believe deeply in the educative value of the contents of this book for all the stakeholders in Fisheries and pharmaceutical Education.
Nature is considered to be an ancient pharmacy serving as the solitary source of therapeutics for thousands of years. Almost all of the current natural product-derived therapeutics have their terrestrial origins. The marine environment has also become a promising source of bioactive molecules and drugs of therapeutic use. Recent research findings have shown that marine organisms possess a higher incidence of significant bioactivity compared with terrestrial organisms. In a National Cancer Institute preclinical cytotoxicity screening, 1% of the examined marine samples exhibited anti-cancer potential versus 0.1% of the tested terrestrial samples. The number of new marine bioactive compounds reported each year is also increasing considerably, and more than 1000 new such compounds have been reported each year. However, the path to drug discovery from marine organisms faces several challenges. Lack of advancements in sampling techniques, taxonomic identification of therapeutically important marine species, compound structure determination strategies, etc. represent crucial steps in marine drug discovery.
The present volume titled “Marine Biopharmaceuticals: Scope and Prospects” the first of its kind is written by both the experts of pharmaceutical and fisheries disciplines and it deals with the pharmaceutically important marine organisms; and their bioactive compounds, chemical classes and modes of action. It also deals with the techniques in the development of marine biota-derived drugs; and the constraints and remedial measures. The chapter on the introduction of an inter-disciplinary PG degree program on the hitherto unknown but productivity course viz. Marine Bio-Pharmacy will help drug companies acquire trained personnel in the development of new marine drugs.
I congratulate the authors for their timely publication for the benefit of the Fisheries and Pharmaceutical sector.
Dr. G. Sugumar
Vice-Chancellor, Tamil Nadu Dr. J. Jayalalithaa Fisheries University
Tamil Nadu
India
PREFACE
Our marine ecosystems including the seas and oceans cover about 70% of the earth’s surface and contain over 80% of the world’s biodiversity. Unfortunately, only 5% of these ecosystems have so far been explored and only 9% (about 200,000) of the total species have been adequately researched. The marine biodiversity is an exceptional reservoir of natural products (bioactive compounds or secondary metabolites) owing to their different structural features from those of terrestrial natural products. During the last 50 years, about 15,000 bioactive compounds with potential applications as medical drugs have been isolated from these species. However, only less than 1% of these compounds have so far been examined for their pharmacological activities. The study of marine organisms for their bioactive potential has therefore increased in recent years. As there is a great demand for the discovery of new medicines, researchers are nowadays increasingly looking towards these marine ecosystems
for the isolation and development of novel compounds, treatments, and solutions to combat human disease.
Though some books are presently available on marine natural products, a comprehensive book on marine biopharmaceuticals and their scope and prospects is still needed. Further, a book dealing with the most promising pharmaceutical compounds derived from the major groups of marine organisms with an aim of utilizing them in the development of new drugs is the need of the hour. Keeping these in consideration, this publication is being brought out for the first time by bringing together the experts in Pharmaceutical Sciences, Marine Biology, and Marine Biochemistry disciplines. Aspects relating to Marine Bioprospecting; Promising Pharmaceutical Compounds of Marine Biota with their Therapeutic Applications; Marine Biopharmaceuticals in the Pipeline; and Scope and Career Prospects of Marine Bio-Pharmacy ( Marine Biopharmaceutical Sciences) and Pharmaceutical Marine Biology courses are dealt with .It is strongly hoped that this title would largely help the researchers and students of disciplines like Marine Bio-Pharmacy, Marine Biology, Marine Microbiology, Marine Biochemistry and Marine Biotechnology; as a standard Reference for all Libraries of Colleges and Universities; and as a guide for the drug companies involved in the development of new drugs from marine biopharmaceuticals.
Santhanam Ramesh
Karuna College of Pharmacy
Kerala University of Health Sciences, Palakkad
Kerala, IndiaRamasamy Santhanam
Fisheries College and Research Institute
Tamil Nadu Veterinary and Animal Sciences University
Thoothukudi, India
&Veintramuthu Sankar
P.S.G. College of Pharmacy
Coimbatore, Tamil Nadu
India
Introduction
Santhanam Ramesh1,Ramasamy Santhanam2,Veintramuthu Sankar3
1 Santhanam Ramesh , Vice-Principal, Karuna College of Pharmacy, Kerala University of Health Sciences, Palakkad, Kerala, India
2 Fisheries College & Res. Instt., Tamil Nadu Veterinary & Animal /sciences University, Thoothukudi,India
3 Department of Pharmaceutics and Vice Principal P.S.G college of Pharmacy, Coimbatore 641 004, Tamil Nadu, India
Abstract
This chapter deals with the role of seas and oceans in human life; marine biodiversity; marine drugs and their origin; groups of marine biota as sources of drugs; importance and advantages of the production of marine drugs; pharmaceutical marine biodiversity in the development of marine drugs; existing problems in the development of new marine drugs; and remedial measures for the adequate supply of bioactive compounds for the production of cost-effective new drugs for various diseases.
Keywords: Marine biodiversity, Marine organisms as drug sources, Origin of marine drugs, Pharmaceutical marine biodiversity, Problems in marine drug development.
Introduction
Although 71% of the earth’s surface is covered in water, 97% of this is found in our seas and oceans. But, only 5% of our oceans have so far been explored. Further, the first marine organisms appeared about 3500 million years ago and even after 250 years of active marine research, only 9% of the species present have been adequately researched and the remaining 91% of the species present in the seas and oceans still lack a detailed description. The marine environment is the richest biosphere on earth and its living conditions differ significantly from those on the earth. The temperature range of this environment is huge as it varies from −1.5°C in ice sea to 350°C in deep hydrothermal systems; pressure from 1 to over 1,000 atmospheres; light from complete darkness to extensive photic zones; and nutritional conditions from nutrient-rich to nutrient-sparse.
Role of Seas and Oceans in Human Life
The seas and oceans play an important role in the human life. As per available reports, about one billion people depend on seafood as their primary source of animal protein. These water bodies are known to produce over half of the oxygen we breathe besides storing 50 times more carbon than the atmosphere. The coastal habitats adjoining the seas such as coral reefs and mangrove swamps provide protection from tsunamis and storms, while the ocean currents regulate largely our
climate and weather systems. The seas and oceans also provide humans with several unique recreational activities which include fishing, boating, and whale watching. These water bodies are also known to help largely in transportation and 76% of all US trade is done involving some form of marine transportation. Recent research on marine organisms has shown that these organisms are the reservoirs of several drug-producing natural products especially for the treatment of cancer, arthritis, Alzheimer’s disease, and heart disease [1].
Marine Biodiversity
Only a fraction of the types of organisms that live in the sea are known today. As per the World Register of Marine Species, there are 240,000 known species (2016, http://www.marinespecies.org/) of which the highest number of species (about 33000) was found in the seas around Australia and Japan. Of the 36 animal phyla so far reported, about half are exclusive to the sea and among the marine animals, 60% belongs to the invertebrates [2].
Origin of Marine Drugs
Throughout history, nature and medicine have shown a strong relation, as highlighted by the wide use of therapeutic biomolecules in traditional medicines for thousands of years. During the ancient Greece and early Byzantium periods, the therapeutic applications of marine invertebrate organisms were deeply rooted in Mediterranean populations. Amazingly these invertebrates were used therapeutically in the forms of beverages, pulverized products, juices, broth, unguent, or eaten as fresh or dry flesh. The use of marine herbs and their formulas belongs to a thousand-year tradition. The Chinese Marine Materia Medica, a kind of encyclopedia is considered to be the best compendium about blue-green algae (cyanobacteria), seaweeds and marine animals. This encyclopedia is also considered the starting point in the development of new marketed drugs. This long tradition amply testifies that the interest in marine natural products developed in the ancient world, though the current research has been emphasizing the beneficial effects of these natural products and their molecules [3].
Marine Organisms as Sources of Drugs
Nowadays, most drugs in use come from nature. For example, while aspirin was first discovered from the willow tree, penicillin was isolated from the common bread mold. Further, the majority of drugs derived from natural sources have their origin from land-dwelling organisms. However, as there is a great demand for the discovery of new medicines, researchers are nowadays increasingly looking towards the ocean. Systematic and continuous searches for new drugs have shown that marine invertebrate organisms are capable of producing several anticancer, antibiotic, and anti-inflammatory substances than any group of terrestrial organisms. Such promising invertebrates include sponges (Porifera), corals and jellies (Cnidaria), flatworms (Platyhelminthes), polychaetes (Annelida), moss animals (Bryozoa), lamp shells (Brachiopoda), crustaceans (Arthropoda), mollusks (Mollusca), sea stars and other echinoderms, (Echinodermata), acorn worms and relatives (Hemichordata), tunicates, (Urochordata) and elasmobranchs and teleost fishes (Chordata). Across these animals, the marine sponges (Porifera) account for almost half of new natural products since 1990. An interesting feature of the habitats of these drug-producing organisms (except the cone snail) is more or less sessile (non-moving) invertebrates. The possible reasons for this phenomenon are: these sessile invertebrates use these chemicals to repel predators because they cannot escape from their habitat easily; and since many of these sessile species are filter feeders, they may use these powerful chemicals to repel parasites or as antibiotics against disease-causing organisms. [2, 4].
Need for the Production of Marine Drugs
Of late, diseases, such as Alzheimer’s and Arthritis have been reported to create greater threats to the quality of human life. Heart disease, on the other hand, has become a major threat, while cures for cancer and AIDS continue to be challenging. Unfortunately, many of the drugs formulated over the past several decades have now become less useful due to the development of drug resistance. Some forms of cancer have evolved multiple drug resistance which has made all drug treatments ineffective. In this context, the organisms of the seas and oceans could be a new source of biodiversity and novel drugs. Unlike the terrestrial environment, ethnomedicinal information to guide marine research is very much limited. It is interesting to know that about one-half of all cancer drug discovery focuses now on marine organisms. It was only after the 1950s, scientists began to explore the seas and oceans for useful therapeutics and this was largely due to the advent of scuba diving and new sampling technologies. Marine drug discovery, however, began in the late 1970s, and programs were formulated in the 1980s in the USA, Japan, and Australia. These programs have led to the development of novel new drug leads. Significant progress in the clinical development of marine-derived drugs has been achieved during the last 20 years and during this period, six out of nine currently used drugs of marine origin have been approved [5].
Pharmaceutical Marine Biodiversity and Drug Development
The high diversity of marine species and associated high competition for survival make their compounds unique in chemical structures and biological activities compared to terrestrial natural products. The marine life yielding bioactive compounds includes mainly microorganisms such as microalgae, cyanobacteria, bacteria, fungi, and other protists; seaweeds (green, brown, and red algae); sponges, cnidarians, bryozoans, molluscs, tunicates and echinoderms; and mangrove plants and other intertidal plants. The number of marine bioactive compounds isolated has increased considerably over the last two decades. As of December 2020, about 36,000 bioactive compounds have been isolated from about 3,400 species. The compounds marketed as drugs or are under drug development are, however, relatively few. It is also worth mentioning here that intensive research has always been focused on the cytotoxic and anticancer activities of these compounds and this is largely due to the fact that the main source of funds for Marine Natural Product Drug Discovery Research in the US was the National Institutes of Health (NIH) / National Cancer Institute (NCI) [5]. It is also reported that only 9,000 marine biopharmaceutical compounds have so far been screened for potential therapeutic value and of these, only 16 have been marketed (11 of them for cancer indications). According to the marine pharmacology/pharmaceutical pipeline website, as of August 2021, there were 30 marine biopharmaceutical compounds in the clinical pipeline, 5 in phase III, 9 in phase II and 16 in phase I [6].
Problems in the Development of New Marine Drugs
Bottleneck in the permanent availability of sufficient amounts of organisms.Difficulties in harvesting the organism.Difficulties in the identification of marine species.Limited quantities of bioactive compounds from original source organisms.Complex chemical structures of bioactive compounds.Difficulties in isolation and purification procedures.Difficulties in synthesizing bioactive compounds.Enormous time it takes to reach the market (i.e. about 12 years to develop one approved drug from about 5,000-10,000 bioactive compounds) and the cost of drug production.Remedial Measures for the Supply of Bioactive Compounds
In order to ensure a sustainable supply of drug candidates, marine biotechnology processes viz. aquaculture/mariculture/ fermenter cultivation, genetic engineering, enzymatic synthesis, chemical synthesis or semi-synthesis need to be encouraged.Sufficient investment by pharmaceutical companies.Enhancing the research in pharmaceutical companies with staff with adequate expertise.Present Status of Marine Drug Discovery
The concept of Marine Bio-pharmacy, Marine Pharmacology, or Marine Pharmacognosy is either new to India or in an infant stage.Although the pharmaceutically important marine species diversity is enormous in India, no intensive research has been done on this aspect due to the absence of an interdisciplinary approach.Although few research papers are presently available on the bioactivities of marine organisms from their extracts, no new bioactive compounds have been isolated from the marine organisms in our country.The existing course viz. ‘Fish Pharmacology’ in the different institutes of India deals with only ‘Drugs for fish diseases in Aquaculture systems’ and not on the pharmaceutical potential of fish.Scope for Active Research on the Development of Marine Drugs
The exploration of the marine environment is increasing in developed countries and this is largely due to the adoption of new techniques for sample collection, and improved spectrometric techniques and separation methods.
Starting of an inter-disciplinary course viz. Marine Bio-Pharmacy \Collaborative research between academic marine scientists with biomedical researchers in the pharmaceutical industries.
CONCLUSION
The recent advances made in the development, approval, and therapeutic use of marine drugs amply reveal the enormous potential of the bioactive compounds derived from marine organisms. However, there are many challenges ahead to further exploit the potential of marine organisms for therapeutic purposes. In this regard, the following aspects need to be given more emphasis [2].
Taxonomy: As the correct taxonomic identification of the bioactive compound-producing marine organism is essential for further processes, this aspect needs to be given top priority.
Supply/cultivation: In order to ensure sustainable supply of marine organisms towards the development of drugs, advancement in sampling techniques needs to be discovered. Such techniques can allow access to marine samples not only near shore but also in the deep sea. Further, special fermentation technologies are to be devised to cultivate organisms living in marine environments under extreme conditions like high pressure.
Market access: As for terrestrial drugs, the requirements to get access to the market are more or less the same for marine-derived drugs. Presently a long time (8-15 year period) is required for the approval of drugs and a significant amount of money (about US$900 million) is involved from the discovery of drugs to market. Further, there is a very high risk in the procedures in the development of new drugs and many drug candidates have failed during the development processes because of toxicity, lack of sustainable availability, etc.
Collaborative venture: Intensive interdisciplinary collaboration between biologists, pharmacists, chemists, biotechnologists, medical doctors, etc., and between universities, hospitals, and companies is the need of the hour in order to make marine pharmaceutical development a great success.
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