J Food Bioact

Journal of Food Bioactives, ISSN 2637-8752 print, 2637-8779 online

Journal website www.isnff-jfb.com

Review

Volume 19, September 2022, pages 4-96

Novel marine bioactives: application in functional foods, nutraceuticals, and pharmaceuticals

Figures

Figure 1. Total number of papers published in each year from 2010 to 2020 related to the exploration of marine-based novel natural components (Carroll et al., 2022, 2021, 2019; Blunt et al., 2018, 2017, 2016, 2015, 2014, 2013, 2012).

Figure 2. Trend of total number of novel marine-based natural compounds identified from 2001 to 2020 (Carroll et al., 2022, 2021, 2019; Blunt et al., 2018, 2017, 2016, 2015, 2014, 2013, 2012, 2011, 2009, 2008, 2007, 2005, 2004, 2003).

Figure 3. Factors contributing to the synthesis of diverse bioactive metabolites by marine species.

Figure 4. Chemical structures of EPA, DHA, and DPA.

Figure 5. Different extraction methods of bioactive peptides.

Figure 6. Chemical structures of the most common carotenoids.

Figure 7. Chemical structures of phlorotannins present in brown algae.

Figure 8. Eight major phyla of marine invertebrates.

Figure 9. Contribution by different phyla for the overall production of natural products by marine invertebrates.

Figure 10. Factors contributing to the production of bioactive compounds by sponges.

Figure 11. Distribution of different biological activities exhibited by natural products isolated from Dictyoceratida sponge.

Figure 12. General body plan of Polyp and Medusa forms of Cnidarians.

Figure 13. Different classes of Cnidarians.

Figure 14. Percentages of different compounds isolated from phylum Cnidaria in the twenty-first century.

Figure 15. Distribution of biological properties exhibited by the compounds isolated from phylum Cnidaria in the twenty-first century.

Figure 16. Structures of important Cembranoids compounds identified from soft corals Sinularia flexibilis and Sinularia sandensis.

Figure 17. Examples of different classes of Echinodermata.

Figure 18. Examples of species belong to the classes Gastropoda, Bivalvia, and Cephalopoda.

Figure 19. Relative proportion of the various chemical classes of secondary metabolites isolated from gastropods since 2000.

Figure 20. Relative proportion of the various chemical classes of secondary metabolites isolated from bivalves since 2000.

Figure 21. Chemical structures of the main carotenoids present in bivalves.

Figure 22. Important metabolites identified from cephalopods. [a - C20 diterpenoid; b - irregular C15 sesquiterpenoid; c - C19 furano norditerpenoid; d – Sterol derivative; e - octahydroazulenopyrandione; f - 14-((Z)-pent-14b-en-14a-yl)-16-propyl-octahydro-furo [1,4,8] trioxacyclohexadecine-12,19-dione; g - methyl 1- acetoxy-hexahydro-3-methyl-3-propyl-1H-isochromene-4-carboxylate; h - methyl 7-ethyl-hexahydro-8a-methyl-2H-chromene-4-carboxylate; i - 11-(hexahydro-8-methoxy-4-methyl-1H-isochromen-4-yloxy)- 11- hydroxyethyl pentanoate; j - methyl 9-(tetrahydro-3-oxo-3H-isochromen-5-yl) hexanoate].

Figure 23. The adult form of ascidians.

Figure 24. (a) Distribution of bioactive compounds identified from ascidians; (b) Distribution of biological activities exhibited by metabolites extracted from ascidians.

Figure 25. Percentages of food products (fillets) and different by-products from fish processing industries.

Figure 26. Major groups of seaweeds (red, brown, and green seaweeds).

Figure 27. Different traditional and novel techniques used to extract bioactive compounds from marine sources.

Tables

**Table 1.** Different bioactive compounds (except peptides, alkaloids, and terpenes) produced by sponges and their biological activities
Compound	Classification of compounds	Species of sponge	Biological activity	References
SW1990 - Human pancreatic adenocarcinoma cell line, PANC-1 - Human pancreatic cancer cell line isolated from a pancreatic carcinoma of ductal cell origin, DU145 - Human prostate cancer cell line, Huh7 - hepatoma tissue cell lines, HepG2 - human liver cancer cell line.
Zampanolides B, C and D	Macrolide	Cacospongia mycofijiensis	Microtubule stabilizing action with anti-mitotic and anti-proliferative properties	Taufa et al., 2018
Gracilosulfates A, B, C, D, E, F and G	Steroid	Haliclona gracilis	Anti-tumor activity on the human prostate cancer cell lines	Shubina et al., 2020
Monacolin X	Polyketide	Monascus sp.	Anti-migratory and anti-proliferative effects on human breast cancer cell lines	Nagabhishek and Madankumar, 2019
Botryorhodines I and J	Depsidones	Setosphaeria sp.	Act as an anti-fungal agent against the phytopathogenic fungi Colletotrichum acutatum and Colletotrichum asianum	Pang et al., 2018b
Osirisynes G, H, and I	Long-chain highly oxygenated polyacetylenes	Haliclona sp.	Enzyme inhibition against proteasome kinase	Campos et al., 2020
Mycalolide A, Mycalolide B, 38-hydroxymycalolide B	Macrolide	Mycale aff. nularosette	Incomplete cytokinesis due to actin depolymerization	Hayashi-Takanaka et al., 2019
19-methoxydictyoceratin-A	Sesquiterpene quinones	Dactylspongia elegans T3	Anti-cancer effect on the human cancer cell lines SW1990, PANC-1, DU145 and Huh7	Yu et al., 2019
5,6-dibromo-8,1′-dihydro-isoplysin A; 6-bromo-8,1′-dihydro-isoplysin A	Tryptophan derived alkaloids	Fascaplysinopsis reticulata	Antibacterial activity against Vibrio sp.	Campos et al., 2019
Lectin	Glycoprotein	Axinella donnani	Anti-biofilm activity against biofilm-producing S. aureus and antibacterial activity against S. aureus bacterial cells	Sadanandan and Rauf, 2018
3,5-dibromo-2-(2,4-dibromophenoxy)-phenol 3,4,5-tribromo-2-(2,4-dibromophenoxy)-phenol	Polybrominated diphenyl ethers	Dysidea sp.	Inhibit the production of Hepatitis B viral cells in the cell line HepG2.2.15.7	Yamashita et al., 2015
Meroterpenes Alisiaquinone A Alisiaquinone B Alisiaquinone C Alisiaquinol		Verongula rigida (New Caledonian deep-sea sponge)	Anti-malarial activity against chloroquinone-resistant Plasmodium falciparum strain and enzymes protein farnesyltransferase and plasmodium kinase Pfnek-1	Desoubzdanne et al., 2008

**Table 2.** Cytotoxic activities exhibited by diverse classes of alkaloids extracted from marine sponges
Alkaloid group	Sponge	Name of the compound	Biological activity	References
MCF-7 - human breast cancer cell lines, HCT-116 - human colorectal carcinoma cell lines, A549 - lung carcinoma cell lines, HT-29 - human colorectal adenocarcinoma cells, MDA-MB-231 – human breast cancer cell lines, L1210 - mouse lymphocytic leukemia cell line, KB - human epithelial carcinoma cells, THP-1 - human leukemia monocytic cell line, A2780 - human ovarian cancer cells, K-562 - myelogenous leukemia cell lines, P388 - lymphocytic leukemia cells, JB6C141 - mouse epidermal cell line, HL-60 - human leukemia cells, HepG2 - human liver cancer cell line, OVCAR - ovary carcinoma cells, HOP-92 - pulmonary carcinoma cells, PC3 - prostatic carcinoma cells, SK-MEL-28 - melanoma cells, UO-31 - kidney carcinoma cells, A431 - human epidermoid carcinoma cells, NSCLC-N6 - human bronchial epidermoid carcinoma cells, MDA-435 - metastatic human breast cancer cells, MRC-5 - human fetal lung fibroblast cells, PC9 - lung adenocarcinoma cell line, HM02 - well-differentiated gastric carcinoma cells, Huh7 - hepatoma tissue cell lines, C-38 - murine adenocarcinoma cell line, OVCAR-3 - ovarian adenocarcinoma cell line, MALME-3M - malignant human melanoma cell line, MM.1S - B lymphoblast cell, Sw620 - human colorectal adenocarcinoma cell lines, HCC-2998 - human colon carcinoma cell line, MOLT-4 - T lymphoblast cell line, mES - mouse embryonic stem, SKBR3 - human breast cancer cell line, B16 - murine tumor cell line, L929- fibroblast cell line, U138 - Colon cancer cells, SF-295 - human glioblastoma cell line, MDA-MB435 - Melanoma cell lines, HCT-8 - Colorectal cancer cell lines, A498 - renal cancer cell lines, PSN1 - human pancreatic adenocarcinoma cell line, LN-caP - prostate adenocarcinoma cell line, PANC-1 - human pancreatic cancer cell line, DU-145 - human prostate cancer cells, SKOV-3, IGROV, IGROV-ET - human ovarian cancer cell line, SK-BR-3 - human breast cancer cell line, MEL-28 - Melanoma cell lines, H-MEC-1 - Human microvascular endothelial cells, LoVo - lymph node metathesis cells, L5178Y - mouse lymphoma cell, SW480 - human colorectal carcinoma cell line, H460 and H292- human non-small-cell lung cancer cells, Du145 - human prostate cancer cells, BE2-C - neuroblastoma cell line, SJ-G2 – glioblastoma cancer cells, MIA - pancreatic cancer cells, SMA and U87 - human glioblastoma cell line, p53^+/+, p53^−/−, p21^+/+, and p21^−/− - isogenic HCT-116 human colon tumor cell lines, AsPC-1, BxPC3, and MIA PaCa2 - human pancreatic tumor cell line, P388D₁ - mouse lymphoma cells, LU-1 - cancer cell line, SK-Mel-2 - human melanoma cell lines, 3Y1 - rat embryo fibroblast cell line, SK-MEL - Human malignant melanoma cells, BT-549 – Breast cancer cell lines, LLC-PK11, CLL - Chronic lymphocytic leukemia, LNCaP - human prostate adenocarcinoma cells, H4IIE - rat hepatoma cell lines.
Acridine alkaloid	Dercitus sp.	Dercitin	Potent cytotoxic activity in nanomolar concentration	Burres et al., 1989
Acridine alkaloid	Xestospongia sp.	Neoamphimedine; 5-methoxyneoamphimedine; Alpkinidine	Selective activity for solid tumors	Thale et al., 2002
β-carbolines	Acanthostrongylophora ingens	Acanthomine A; 1,2,3,4-tetrahydronorharman-1-one; Ingenine E; Annomontine	Potent cytotoxicity against human breast cancer (MCF7), colorectal carcinoma (HCT116), and lung carcinoma (A549) cell lines	Ibrahim and Mohamed, 2017
Bromotyrosine	Jaspis sp.; Bubaris sp.	Aplyzanzine B	Strong cytotoxicity against human lung carcinoma epithelial cells (A549), colorectal adenocarcinoma(HT-29), and breast cancer (MDA-MB-231) cell lines	Tarazona et al., 2017
	Hexadella sp.	Anomoian B		Tarazona et al., 2017
	Suberea sp.	Ma’edamines C; Ma’edamines D	Selective cytotoxicity on murine leukemia L1210 cell line	Kurimoto et al., 2019
	Suberea sp.	Suberedamine A; Suberedamine B	Potent cytotoxic activity against mouse lymphocytic leukemia (L1210) and human epithelial carcinoma (KB) cell lines	Tsuda et al., 2001
	Psammoclemma sp.	Psammaplysene C; Psammaplysene D	Potent cytotoxic activities against human leukemia monocytic (THP-1) cell line	Buchanan et al., 2007
	Druinella sp.	Purealidin S; Purpuramine J PurealidinQ; Aplysamine 2 Purpureamine I Aerophobin 2; Aerophobin1; Purealidin J; Araplysillin1; Araplysillin 2	Potent to moderate cytotoxic activities against human ovarian cancer (A2780) and myelogenous leukemia (K562) cell lines	Tabudravu and Jaspars, 2002
Dibrominated and Brominated	Agelas dendromorpha	Agelastatin E	Strong cytotoxicity against human epithelial carcinoma (KB) cell lines	Tilvi et al., 2010
	Suberea sp.	Aerothionin	Potent cytotoxicity against HeLa cells	Shaala et al., 2015
	Psammoclemma sp.	Echinosulfonic acid D; Echinosulfonic acid B	Potent cytotoxicity against human epithelial carcinoma (KB) cell lines	Rubnov et al., 2005
Aaptamine	Aaptos suberitoides	Aaptamine; Isoaaptamine; Demethylaaptamine	Proteasome inhibitory action and potent cytotoxicity against HeLa cell lines	Tsukamoto et al., 2010
Aaptamine	Aaptos suberitoides	Suberitine A; Suberitine B; Suberitine C; Suberitine D	Selective and potent cytotoxicity against lymphocytic leukemia (P388), HeLa and myelogenous leukemia (K562) cell lines	Liu et al., 2012a
Guanidine	Monanchora pulchra	Monanchocidin A	Potent cytotoxicity against monocytic anemia cell lines THP-1, Hela, and JB6C141 cell lines	Guzii et al., 2010
	Monanchora pulchra	Monanchocidin B–E	Strong inhibitory activity against human leukemia (HL-60) cells	Makarieva et al., 2011
	Crame crame	Crambescidin-816	Reduce cell viability of human liver cancer (HepG2) cell line; Affect the human tumor cell lines such as ovary carcinoma (OVCAR), pulmonary carcinoma (HOP-92), breast cancer cells (MCF-7), prostatic carcinoma (PC3), melanoma (SK-MEL-28), kidney carcinoma (UO-31), and colorectal adenocarcinoma (HT-29)	Rubiolo et al., 2014
	Clathria bulbotoxa	Crambescidins 345; Crambescidins 361; Crambescidins 373; Crambescidins 359; Crambescidins 657	Cytotoxic activity against human epidermoid carcinoma (A431) cell line	Kasmiati et al., 2018
	Monanchora pulchra	Normonanchocidin A; Normonanchocidin B; Normonanchocidin D	Cytotoxicity against human leukemia monocytic (THP-1) and HeLa cells	Tabakmakher et al., 2015
		Monanchomycalin C; Ptilomycalin A	Effect the human breast cancer (MDA-MB-231) cells	Tabakmakher et al., 2013
		Monanchoxymycalin C	Inhibit the colony formation of HeLa cells	Shubina et al., 2019
	Biemna laboutei	Netamine M; Netamine O; Netamine Q	Potent cytotoxicity against human epithelial carcinoma (KB) cell line	Gros et al., 2014, 2015
	Anchinoe pauperta	Zanissine	Cytotoxic effects on murine pre- B cell lymphoma (P-388), KB, and human bronchial epidermoid carcinoma (NSCLC-N6) cell lines	Bouaicha et al., 1994
	Monanchora sp.	Unguiculin A; Unguiculin B; Unguiculin C	Potent effect against KB cancer cell lines	El-Demerdash et al., 2018
	Monanchora sp.	Monanchoradin A; Dehydrocrambescin A2 418; Crambescidin 786; (−)-crambescidin 814; Monalidine A; (–)-crambescin 406; Crambescidin 800; Crambescidin 826; 20-norcrambescidic acid	Cytotoxic activity against human colorectal carcinoma cell (HCT-116), metastatic human breast cancer (MDA-435), human leukemia cells (HL-60), KB, and MRC-5 cell lines	El-Demerdash et al., 2016
Imidazole	Leucetta chagosensis	(−)-calcaridine; (2E, 9E)-pyronaamidine-9-(N-methylimine)	Selective cytotoxicity against MCF-7 cell lines	Tang et al., 2019
	Pericharax heteroraphis	Naamidine J	Inhibited the growth of human breast cancer (K562) cell line	Wei et al., 2020
	Pericharax heteroraphis	Naamidine H	Inhibitory effect on K562, HeLa, and adenocarcinomic human alveolar basal epithelial cells (A549) cell lines	Wei et al., 2020
	Leucandra sp.	Naamine J	Inhibitory effect on MCF-7, A549, HeLa, and PC9 cell lines	Tang et al., 2016
	Leucetta chagosensis	Naamidine I; Naamidine H	Cytotoxic effect on the HeLa cell line	Tsukamoto et al., 2007
		Isonaamine C; Isonaamidine E	Growth inhibitory effect HM02, hepatocellular carcinoma (HepG2), and hepatoma tissue (Huh7) cell lines	Gross et al., 2002
		Chagosendine B; Chagosendine C	Potent inhibition against K562, HepG2, and HeLa cell lines	An et al., 2018
		Pyronaamidine	Inhibited K562 and HeLa cell lines	An et al., 2018
	Leucosolenia sp.	Leucosolenamine B	Potent cytotoxic effect on the C-38 cell line	Ralifo et al., 2007
Indole, Bisindole, and Trisindole	Thorectandra sp.	Demethoxyfascaplysin	Cytotoxic effects on breast cancer cell line	Charan et al., 2004
		1-deoxysecofascaplysin A	Inhibited the growth of MCF-7, OVCAR-3, and A549
		Fascaplysin	Cytotoxicity against MCF-7, OVCAR-3, MALME-3M and A549
	Lipastrotethya sp.	Dragmacidin G; Dragmacidin H; Topsentin B2 (bromotopsentin) Topsentin; B1 (topsentin)	Cytotoxic effect on HeLa cells	Hitora et al., 2016
	Hyrtios sp.	Hyrtinadine A	Potent cytotoxicity on L1210 and KB cell lines	Endo et al., 2007
	Hyrtios erectus	Hyrtioerectine A; Hyrtioerectine B; Hyrtioerectine C	Cytotoxic effects on HeLa cell line	Youssef, 2005
	Callyspongia siphonella	5-bromotrisindoline; 6-bromotrisindoline	Inhibitory effect on HT-29, OVCAR-3, and MM.1S cell line	El-Hawary et al., 2019
	Smenospongia sp.	5-bromo-l-tryptophan; 5-bromoabrine; 5,6-dibromoabrine; 5-bromoindole-3-acetic acid	Least cytotoxicity in a set of isogenic HCT116 cell lines	Tasdemir et al., 2002
	Damiria sp.	Damirine A	Cytotoxic effect on MALME-3M, Sw620, HCC-2998, MOLT-4, and k562 cell lines	Tran et al., 2019
	Spongosorites sp.	6″-Debromohamacanthin A (DBHA)	Cytotoxic effect in mES cell line over 20 µM	Kim et al., 2013
Peptide alkaloid	Scleritoderma nodosum	Scleritodermin A	Cytotoxicity on HCT116, A2780, and SKBR3 cell lines	Schmidt et al., 2004
Piperidine alkaloid	Arenosclera brasiliensis	Arenosclerin B; Arenosclerin C; Haliclonacyclamine E	Cytotoxic effects on HL-60, B16, L929, and U138 cancer cell lines	Torres et al., 2002
	Pachychalina alcaloidifera	Madangamine F; Haliclonacyclamine F; Arenosclerins D; Arenosclerins E	Cytotoxicity on on SF295, MDA-MB435, HCT8, and HL60 cell lines	de Oliveira et al., 2007
	Neopetrosia proxima	Neopetrosiamine A	Inhibitory effect on MALME-3M, CCRF-CEM, and MCF7	Wei et al., 2010a
	Mycale sp.	1,5-diazacyclohenicosane	cytotoxic activity against A549, HT29, and MDA-MB-231	Coello et al., 2009
	Pachychalina sp.	Ingenamine G	Potent cytotoxicity against HCT-8, B16, and MCF-7	de Oliveira et al., 2004
	Neopetrosia cf exigua	Papuamine; Haliclonadiamine	Effect on human glioblastoma cell line (SF-295), and human renal cancer cell lines (UO-31 and A498)	Liang et al., 2015
	Haliclona sp.	Papuamine	Cytotoxicity on MCF-7 cell	Kanno et al., 2013
Pyrimidine alkaloid	Theonella swinhoei	Lanesoic acid	Selective cytotoxicity against PSN1cells	Rodríguez et al., 2016
Pyrimidine alkaloid	Kirkpatrickia variolosa	Variolin B	Potent activity against several cell lines including prostate adenocarcinoma cell line (LN-caP), K-562, PANC-1, HT-29, DU-145, SKOV-3, IGROV, IGROV-ET, SK-BR-3, MEL-28, H-MEC-1 and A-549, and LoVo, cell lines	Fresneda et al., 2006
Pyridine alkaloids	Haliclona sp.	Cyano-3-dodecyl pyridine	Moderate cytotoxicity against A549, MCF-7 and HeLa cell lines	Zhang et al., 2016a
	Amphimedon sp.	Amphimedoside A; Amphimedoside B; Amphimedoside C; Amphimedoside D; Amphimedoside E	Cytotoxicity against P388 cell lines	Takekawa et al., 2006
	Xestospongia sp.	N-methylniphatyne A	Potent cytotoxicity against PANC-1 cells	Tsukamoto et al., 2000
	Niphates sp.	Niphatyne A	Cytotoxic effect on P388 cells	Arai et al., 2016
	Amphimedon sp.	Pyrinodemin B–D	Strong cytotoxicity on L1210 and KB cell lines	Hirano et al., 2000
	Cribrochalina sp.	Pyrinadines B–G	Potent cytotoxic effects on L1210 cell line	Kariya et al., 2006
Pyrrole and Bromopyrrole	Stylissa carteri	(+)-dibromophakelline; (Z)-3-bromohymenialdisine	Cytotoxic effects with inhibition of growth of L5178Y cell line	Hamed et al., 2018
Pyrrole and Bromopyrrole	Agelas oroides	Oroidin	Cytotoxic activity on MCF-7, A2780, HT-29, SW480, H460, A431, Du145, BE2-C, SJ-G2, MIA, SMA, and U87 cell lines	Dyson et al., 2014
Pyrroloimino-quinone	Latrunculia brevis	Discorhabdin L; Discorhabdin I	Potent cytotoxic effects on the HT-29 cell line	Reyes et al., 2004
	Smenospongia sp.	Makaluvamine O	Activity against p53^+/+, p53^−/−, p21^+/+, and p21^−/− cell lines	Tasdemir et al., 2002
	Zyzzya cf. fuliginosa	Makaluvamine P	Inhibitory effect on the KB cell line	Casapullo et al., 2001
	Batzella sp.	Isobatzelline A; Isobatzelline C; Isobatzelline D; Isobatzelline E	Cytotoxicity in all pancreatic cell lines (AsPC-1, BxPC3, and MIA PaCa2)	Guzmán et al., 2009
Quinoline and Quinolizinde	Xestospongia sponge	Renierol	Potent cytotoxic activity against L1210 cell line	McKee and Ireland, 1987
	Suberea sponge	Lihouidine	Moderate cytotoxicity against P388D cell line	Bowden et al., 2004
	Reniera sarai	Saraine A–C; Saraine 1-3	Preliminary cytotoxicity in the brine shrimp cytotoxic bioassay	Caprioli et al., 1992
	Xestospongia muta	Meso-araguspongine C; Araguspongines A, C, E, L, N−P	Cytotoxic activities against human cancer cell lines HepG-2, HL-60, LU-1, MCF-7, and SK-Mel-2.	Dung et al., 2019
Tetrahydro- isoqouinoline	Jorunnaf unebris Xestospongia sp.	Jorunnamycin A	Potent cytotoxic activity versus H292 and H460 cell line	Sirimangkalakitti et al., 2016
	Genera Reniera, Haliclona, Xestospongia, Neopetrosia, and Cribrochalina Xestospongia sp.	Renieramycin M	Potent cytotoxic activity versus H292 and H460 cell line	Sirimangkalakitti et al., 2016
	Neopetrosia sp.	Renieramycin J	Powerful cytotoxicity on 3Y1, HeLa, and P388 cells	Oku et al., 2003
Steroidal alkaloid	Corticium niger	Plakinamine I–K; Dihydroplakinamine K	Potent cytotoxicity against HCT-116 cell lines	Ridley and Faulkner, 2003
Steroidal alkaloid	Corticium niger	Plakinamine N; Plakinamine O; Plakinamine J	Enhanced inhibitory effects against all of the colon cell lines	Sunassee et al., 2014
Manzamine	Acanthostrongylophora ingens	(+)-8-hydroxymanzamine A; (+)-manzamine A	Cytotoxic effects against SK-MEL, KB, BT-549, HepG2, and LLC-PK11 cell lines	Samoylenko et al., 2009
Diterpene	Agelas citrina	Agelasine E	Potent cytotoxicity against CLL cell line	Stout et al., 2012
	Fasciospongia sp.	19-oxofasciospongine A	Cytotoxic effect on LNCaP, LU-1, and MCF-7 cell lines	Yao et al., 2009
	Agelas nakamurai	Isoagelasine C	Effect on HCT-116, K562, and HL-60 cell lines	Chu et al., 2017
Sesquiterpene Quinones/ Hydroquinones	Dysidea avara	(−)-4′-methylaminoavarone	Weak toxicity against HCT116 and H4IIE cell lines	Imperatore et al., 2020; Hamed et al., 2013
		(−)-N-methylmelemeleone-A	Weak cytotoxic activity on L5178Y, HCT116, and H4IIE cell lines
		(−)-3′-methylaminoavarone	High cytotoxic activity L5178Y and weak toxicity against HCT116 and H4IIE cell lines

**Table 3.** Biological activities of different compounds isolated from the order Alcyonacea
Group of compounds	Species	Compound	Bioactivity	References
CAKI-1 - human clear cell renal cell carcinoma, EKVX - human lung adenocarcinoma cell line, Daoy - human medulloblastoma, HEp-2 - human laryngeal carcinoma, WiDr - human colon adenocarcinoma, MCF-7 - human breast adenocarcinoma, P-388 - lymphocytic leukemia cells, A-549 - lung carcinoma epithelial cells, HT-29 - human colon cancer cell line, AGS - human gastric adenocarcinoma hyperdiploid cell line, DLD-1 - human colorectal adenocarcinoma, IMR-90 - human diploid lung fibroblast, MOLT-4 - human T lymphocyte leukemia cells, P388D1 - murine macrophage cells, CCRF-CEM- human T-cell acute lymphoblastic leukemia, HL-60- human premyelocytic leukemia, NBT-T2 - Nara Bladder Tumor II, HCMV - Human cytomegalovirus, Hep3B and HepG2 - human hepatocellular carcinoma, iNOS - Inducible nitric oxide synthase, HSV-1 - herpes simplex virus type 1, RKO - human colon tumor cells, HCT116 - human colon cancer cell line, COX-2 - cyclooxygenase-2.
Diterpenoid	Clavularia sp.	Stolonidiol	Effect on nervous system (Potent choline acetyltransferase inducible activity at 0.01−10 μg/mL levels)	Yabe et al., 2000
	Clavularia koellikeri	Cembrane-type diterpenoid	Cytotoxic effect on human colorectal adenocarcinoma cells (IC₅₀ 4.2 μg/mL) and potent growth inhibitory activity against human T lymphocytic leukemia cells (IC₅₀ 0.9 μg/mL)	Iwashima et al., 2000
	Junceella juncea	Juncin ZII	Antifoulant effect towards the settlement of barnacle Balanus amphitrite larva at nontoxic concentrations with EC₅₀ values of 0.004	Qi et al., 2009
	Antillogorgia bipinnata	Caucanolide A and D	In vitro antiplasmodial effect towards the malaria parasite, Plasmodium falciparum	Ospina et al., 2005
	Antillogorgia elisabethae	Pseudopterosin P and Q	Antimicrobial activity against the Gram-positive bacteria Enterococcus faecalis, Staphylococcus aureus, and Streptococcus pyogenes at a dose of 25 μg/ml.	Ata et al., 2004
		Ileabethoxazole	Antituberculosis (92% inhibition of Mycobacterium tuberculosis H₃₇Rv at the levels of 128–64 μg/mL)	Rodríguez et al., 2006
		Homopseudopteroxazole	Antituberculosis (80% growth inhibitory effect towards M. tuberculosis H₃₇Rv at the concentration of 12.5 μg/mL)	Rodríguez and Rodríguez, 2003
		Elisapterosin B	In vitro anti-tuberculosis activity (79% inhibitory effect towards M. tuberculosis H₃₇Rv at a concentration of 12.5 μg/mL)	Rodriguez et al., 2000
		Aberrarone	In vitro antimalarial effect on a chloroquine-resistant strain of the protozoan parasite Plasmodium falciparum (IC50 = 10 μg/mL)	Rodríguez et al., 2009
	Antillogorgia kallos	Bielschowskysin	Antimalarial activity against Plasmodium falciparum (IC₅₀ = 10 μg/mL) Antitumor effect towards the CAKI-1 (GI₅₀ = 0.51 μM) and EKVX (GI₅₀ < 0.01 μM) cell lines	Marrero et al., 2004
	Leptogorgia virgulata	Pukalide; Epoxypukalide	Antifoulant activity (inhibit barnacle settlement with EC₅₀ values ranging from 19 to 55 ng/ml)	Gerhart et al., 1988
	Eunicea sp.	Dolabellanes	Antimalarial effect towards the protozoan parasite Plasmodium falciparum with IC₅₀ values ranging from 9.4–59.6 μM	Wei et al., 2010b
	Eunicea fusca	Fuscoside A and B	Anti-inflammatory activity with potency similar to manoalide and indomethacin; Fuscoside B selectively prevent the synthesis of leukotrienes LTB₄ and LTC₄	Shin and Fenical, 1991
	Eunicea fusca	Fuscoside E	Strong anti-inflammatory activity and antifouling activity against bacterial strains	Reina et al., 2011
	Asterospicularia laurae	Asterolaurin L	Moderate antitumor activity against Daoy, HEp-2, WiDr, and MCF-7 with ED₅₀ values of 6.23, 4.12, 6.08, and 4.09 μg/ml, respectively	Lin et al., 2011
	Cespitularia hypotentaculata	Cespitularin A–E	Cespitularin C showed potent cytotoxicity against P-388 and A549 cells; Cespitularin E exhibited strong cytotoxic effect against A549 cells; Cespitularins A, B, and D exhibited moderate cytotoxicity towards P-388 cells (With an ED₅₀ of ≤4.0 μg/mL)	Duh et al., 2002
	Xenia novaebritanniae	Xeniolide I	Antibacterial effect at a concentration of 1.25 μg/ml	Bishara et al., 2006
	Xenia novaebritanniae	Novaxenicin B	Induce apoptosis in transformed mammalian cells at the levels of 1.25 μg/ml	Bishara et al., 2006
	Xenia plicata	Blumiolide C	Strong cytotoxicity against P-388 and HT-29 cells with an ED₅₀ of ≤4.0 μg/mL	El-Gamal et al., 2005
	Xenia plicata	Blumiolide A and B	Moderate cytotoxicity against P-388 cells with an ED₅₀ of ≤4.0 μg/mL	El-Gamal et al., 2005
Terpenoid	Junceella fragilis	Frajunolides C; Junceellolide E; 11α,20α-Epoxy-4-deacetoxyjunceellolide D	Mild anti-inflammatory effect at a concentration of 10 μg/ml	Shen et al., 2007
	Antillogorgia bipinnata	Bipinnapterolide B	Antituberculosis (66% inhibition against the growth of Mycobacterium tuberculosis H₃₇Rv at 128 μg/mL)	Ospina et al., 2007
	Antillogorgia elisabethae	Caribenols A and B	Strong inhibitory effect against the growth of Mycobacterium tuberculosis H₃₇Rv at a concentration range of 128−64 μg/mL	Wei et al., 2007
	Antillogorgia rigida	Curcuphenol	Antibacterial activity	McEnroe and Fenical, 1978
	Isis hippuris	Suberosenol A	Potent cytotoxicity toward the above three cancer cells with an ED₅₀ value of ≤ 4.0 μg/mL	Sheu et al., 2000
	Isis hippuris	Suberosenol C	potent activity against the growth of P-388 and HT-29 cells with an ED₅₀ value of ≤ 4.0 μg/mL	Sheu et al., 2000
Prostanoid	Clavularia viridis	Claviridic acid A–D; Clavulones I–III	Cytotoxic activity against AGS tumor cells	Lin et al., 2008
		Halogenated prostanoids	Cytotoxicity against DLD-1, IMR-90, and MOLT-4 cells at IC₅₀ values of 0.6, 4.5, and 0.52 μg/mL, respectively	Watanabe et al., 2001
		Claviridin A–D	Potent cytotoxic activity against four human cancer cells of Doay, Hep2, epitheloid carcinoma (HeLa), and WiDr	Shen et al., 2010
Steroid	Clavularia viridis	Yonarasterols A, B, C, and E	Antitumor activity against human colorectal adenocarcinoma cells at IC₅₀ 3, 3, 50, and 0.02 μg/ml, respectively	Iwashima et al., 2001
	Carijoa sp.	Carijoside A	Anti-inflammatory activity (effects on elastase release (IC₅₀ = 6.8 μg/mL) and superoxide anion generation (IC₅₀ = 1.8 μg/mL) by human neutrophils; Moderate cytotoxicity against P388D1, DLD-1, CCRF-CEM, and HL-60 cell lines with ED₅₀ of 10.4, 9.7, 13.1, and 12.0 μg/mL, respectively	Liu et al., 2010
	Pseudopterogorgia sp.	Secosterols	Moderate inhibitory activity towards protein kinase C and potential anti-inflammatory and antiproliferative activity	He et al., 1995
	Isis hippuris	Polyoxygenated gorgosterol (steroids)	Moderate cytotoxic effect against cultured NBT-T2 cells	Uddin et al., 2011
		Polyoxygenated steroid	Inhibitory activity against HCMV, with an EC₅₀ values of 2.0 μg/mL; Cytotoxicity against P-388 and A-549 cell lines with ED₅₀ values of 3.2 and 3.86 μg/mL, respectively	Chen et al., 2011
		Isishippuric acid B	Potent cytotoxicity againstA549, P-388, and HT-29 tumor cells with ED₅₀ values < 0.1 μg/mL	Sheu et al., 2004
		A-nor-22-epi-hippurin-2α-carboxylic acid	Antitumor activity against Hep3B and HepG2 cells with ED₅₀ values at 6.9 and 3.6 μg/mL, respectively	Sheu et al., 2004
	Dendronephthya sp.	Isogosterones A–D	Antifoulant activity (Prevent the settlement of the barnacle Balanus amphitrite larva with an EC₅₀ value of 2.2 μg/mL)	Tomono et al., 1999
Sesquiterpenoid	Lemnalia flava	Flavalin A and B	Neuroprotective activity	Lu et al., 2011a
	Lemnalia flava	Flavalin A	Anti-inflammatory activity (Dose-dependent inhibition of iNOS protein expression)	Lu et al., 2011a
	Paralemnalia thyrsoides	Paralemnolin Q and S	Neuroprotective activity	Huang et al., 2011
	Echinogorgia pseudosassapo	3β-methoxyguaian-10(14)-en-2β-ol	Antifoulant activity (antilarval effect against Balanus amphitrite larvae with EC₅₀ value of 17.2 μg/mL and 50% inhibition towards the larval settlement of B. neritina at levels of 25 μg/mL); Mild anti-HSV-1 activity	Gao et al., 2011
Pyridine	Leptogorgia setacea; L. virgulata	Homarine (N-methyl-2-carboxypyridine)	Potential antifoulant activity (inhibited the growth of diatoms)	Targett et al., 1983
Prostaglandin	Telesto riisei	Punaglandins	Antiproliferative activity (Induce apoptosis in RKO cells); Inhibit the activity of isopeptidase	Verbitski et al., 2004
Dialkylamine	Antillogorgia acerosa	Bis(pseudopterane) amine	Antitumor activity against the HCT116 and HeLa cancer cell lines with the IC₅₀ values of 4.2 μM and 42 μM	Kate et al., 2009
Ergostanoid	Nephthea erecta	Ergostanoids	Anti-inflammatory activity (Decrease the levels of the iNOS and COX-2 protein); Cytotoxicity towards P-388 cell line with an ED₅₀ value of 3.7 μg/mL	Cheng et al., 2009
Secosteroid	Astrogorgia sp.	Astrogorgols	Inhibitory effects against human tumor related protein kinases	Lai et al., 2011

**Table 4.** Bioactive compounds isolated from different classes of Echinodermata and their biological activities
Class of Echinodermata	Organism	Bioactive compounds	Group of the compounds	Biological activity	Reference
Holothuroidea	Isostichopus badionotus	Fucosylated chondroitin sulfate	Sulfated polysaccharides	Anticoagulant; Antiparasitic	Marques et al., 2016
	Cucumaria frondose; Thelenota ananas	Fucosylated chondroitin sulfate	Sulfated polysaccharides	Antihyperglycemic; Anticoagulant; Antithrombin; Insulin-sensitizing; Antiviral	Hu et al., 2014b; Huang et al., 2013
	Ludwigothurea grisea	Fucosylated chondroitin sulfate, Glycosaminoglycans	Sulfated; polysaccharides	Antiparasitic; Anticoagulant; Antithrombin	Marques et al., 2016; Borsig et al., 2007
	A. japonicus	Glucosamine; Galactosamine	Polysaccharides	Antihyperlipidemic; Antioxidant	Liu et al., 2012b
	S. japonicus	Holotoxin	Triterpene glycosides	Antifungal	Yano et al., 2013
	Acaudina molpadioides	ACE inhibitory peptide	Peptide	Antihypertension	Zhao et al., 2009
	Holothuria scabra	T-antigen-binding lectin	Peptide	Antibacterial	Gowda et al., 2008
	Acaudina molpadioide; Bohadschia argus	Cerebrosides, galactocerebrosides, AMC-2	Lipid	Anticancer; Antihyperlipidemic	Ikeda et al., 2009; Zhang et al., 2012a; Du et al., 2015
	Holothuria atra	Lysophosphatidylcholine; L-PAF	Lysophospholipid	Anti-inflammatory	Nishikawa et al., 2015
	S. japonicus, Acaudina; molpadioides	Cerebroside	Sphingolipid	Antioxidant	Duan et al., 2016; Xu et al., 2011a
	Holothuria parva	(Z)2,3-DPAN	Phenolic compounds	Anticancer	Amidi et al., 2017
	Plesiocolochirus minaeus	β-carotene, echinenone, canthaxanthin, etc.	Pigments	Antioxidant	Maoka et al., 2015
	C. frondosa	Frondanol A5	Saponin	Anticancer	Jia et al., 2016; Janakiram et al., 2015
	S. japonicus	SJAMP	Mucopolysaccharide	Antitumor; Immunomodulatory	Song et al., 2013
Asteroidea	Henricia leviuscula	Laeviusculosides	Polyhydroxysteroids	Hemolytic; Cytotoxic activity	Fedorov et al., 2008; Ivanchina et al., 2006
	Asteropsis carinifera	Thornasteroside A	Asterosaponins	Antitumor	Malyarenko et al., 2012
	Linckia laevigata	Hexadecanoic acid	Lipids	Antifouling	Guenther et al., 2009
Ophiuroidea	Ophiomastix mixta	2,3-Dimethyl butenolide	Terpene	Antitumor	Lee et al., 2007
	Astrotoma agassizii	Polyhydroxysterols	Steroidal compound	Antiviral	Comin et al., 1999
	Ophiarachna incrassata	Steroidal glycosides	Steroidal glycosides	Antiviral	D’Auria et al., 1993
	Ophioderma longicauda	Ophioxanthin	Carotenoid	Antioxidant	D’Auria et al.,1985
Echinoidea	Diadema setosum	DSG-A	Ganglioside	Neuritogenic	Yamada et al., 2008
	Lytechinus variegatus	Sulfated fucan	Polysaccharide	Anticoagulant	Pereira et al., 1999
	Heliocidaris crassispina	Echinochrome A	Naphthoquinoid pigment	Anti-inflammatory; Antimicrobial; Antioxidant; Antitoxic agents	Jeong et al., 2014; Berdyshev et al., 2007
	Strongylocentrotus droebachiensis	Strongylocins	Peptides	Antimicrobial	Li et al., 2008b
Crinoidea	Comanthus parvicirrus	Naphthopyrones comaparvin	Naphthopyrones	Anti-inflammatory	Chen et al., 2014; Chovolou et al., 2011
	Neogymnocrinus richeri	Gymnochrome D	Anthraquinoid pigments	Antiviral	Laille et al., 1998
	Anneissia bennetti	Rhodoptilometrin, crinemodin	Polyketides	Antipredatory	Rideout et al., 1979

**Table 5.** Some of the important gastropod metabolites discovered since 2000
Species	Compound	References
D. auricularia	Dolabellol A (Bromo-chloro-diterpenoid)	Machida et al., 2017
Phyllidiella pustulosa	Pustulosaisonitriles, 1–3 (Isonitriles)	White et al., 2017
Spurilla neapolitana	Spurillin A (Cyclohexenyl terpenoid)	Ciavatta et al., 2017
Spurilla sp.	Farnesol derivative
Spurilla sp.	Spurillin B (Diterpene)
Phyllodesmium longicirrum	Methylsarcoate analog	Bogdanov et al., 2017
	2R secogorgosterol
	Bisepoxide
	Isosarcophine
Charcotia granulosa	Granuloside (Linear homosesterterpene)	Cutignano et al., 2015
Onchidium sp.	Pyranone ester derivatives or analogs	Carbone et al., 2013
Thuridilla splendens	Thuridillins (Diterpene metabolites)	Somerville et al., 2012
Aplysia californica (Sea hare) – from ink	Mycosporine-type of amino acids	Kamio et al., 2011
Philinopsis speciosa and Bulla occidentalis	Niuhinone A–C (Polypropionate derivatives)	Cutignano et al., 2011
Doto pinnatida	Guanidine-bound terpene derivative	Putz et al., 2011
Phyllodesmium magnum	Asteriscane sesquiterpenoid	Mao et al., 2011
Tritoniopsis elegans	Tritoniopsin A–D (Pyran- enclosed cladiellane diterpene derivatives)	Ciavatta et al., 2011
Tambja ceutae	Tambjamine K (Isopentyl containing alkaloid)	Carbone et al., 2010
Aplysia fasciata (sea hare)	Sesquiterpenoids	Ioannou et al., 2009
	Acetogenin
	Diterpenoid
Cadlinalutero marginata	Ansellone A (Sesterterpenoid)	Daoust et al., 2010
Austrodoris kerguelenensis	Palmadorin A–C (Clerodane diterpenes)	Diyabalanage et al., 2010
Aplysiopsis formosa (slug)	Aplysiopsene A–D (α-pyrone polyketides)	Ciavatta et al., 2009
Onchidiopsis variegate	Ketosteroid derivative	Santalova et al., 2007
Scaphander lignarius	Lignarenones (Aromatic benzene-enclosed compounds)	Sala et al., 2007
Haminoea fusari	Fusaripyrones A and B (Polypropionate analogs)	Cutignano et al., 2007
Bursatella leachii (sea hare)	7R-configured malyngamide	Suntornchashwej et al., 2007
H. sanguineus (Spanish dancer mollusc)	Sesquiterpenoid	Zhang et al., 2007b
H. sanguineus (Spanish dancer mollusc)	Diterpenoid	Zhang et al., 2007b
Siphonaria lessoni	Siphonarienolone	Rovirosa and San-Martín, 2006
Elysia cf. expansa	Dihydrocaulerpenyne	Ciavatta et al., 2006
Elysia cf. expansa	Expansinol	Ciavatta et al., 2006
Elysia diomedea	Elysiapyrone metabolites A–B	Cueto et al., 2005
D. pelseneeri	15- acetoxy-ent-pallescensin-A	Gaspar et al., 2005
	Dendocarbin-A
	Euryfuran
	Drimane ester mixture
A. parvula	(3Z)-bromofucin	McPhail and Davies-Coleman, 2005
Syphonota geographica	Aplykurodinone 1–2	Gavagnin et al., 2005
Doriopsilla pelseneeri	Pelseneeriols-1 and 2 (Furanosesquiterpene alcohol derivatives)	Gaspar et al., 2005
Phyllidiella pustulosa	Sesquiterpenes	Manzo et al., 2004
A. kerguelenensis	Austrodoric acid	Gavagnin et al., 2003
Placida dendritica	Placidenes C–F (Asymmetrical polypropionate derivatives)	Cutignano et al., 2003
Aldisas maragdina	Progesterone analog	Gavagnin et al., 2002
A. dactylomela	Johnstonol	Kaiser et al., 2001
	Pacifenediol
	Pacifidiene
	Tryptophan-based dipeptides	Appleton et al., 2001
A. dactylomela	Puertitol-B acetate (Sesquiterpenes)	Wessels et al., 2000
	Caespitenone (Sesquiterpenes)
	8-acetyl-caespitol (Sesquiterpenes)
	Dactylopyranoid (Diterpenoids)
	Isopinnatol B (Diterpenoids)
P. ocellatus	Tridachiapyrones G–J (Polypropionate pyrones)	Fu et al., 2000
P. ocellatus	Tridachiahydropyrons B–C (Polypropionate pyrones)	Fu et al., 2000
Asco bullaulla	Ascobullins A and B (Sesquiterpenes)	Gavagnin et al., 2000

**Table 6.** Some of the important metabolites produced by bivalves since 2000
Species	Compound	References
V. cyprinoides (Corbiculid clam)	19-(10→5) abeo-20-methyl-pregnenyl-3-hexenoate (Abeo-pregnane-type sterol derivative)	Joy and Chakraborty, 2018a
	241, 242 dihomocholesta-5, 22, 241-trienol (Cholestenols)
	241- homocholesta-5, 22-dien-3, 241-diol (Cholestenols)
P. malabarica	C18 sesquiterpenoid with prenylated irregular farnesene framework (2H-pyranoids)	Joy and Chakraborty, 2017a, 2017b
	C21 prenylated bisabolene-type meroterpenoid (2H-pyranoids)
	18 (4 →14), 19 (4 → 8)-bis-abeo C19 norditerpenoid (Isopimarane derivative)
M. galloprovincialis	Carotenoids (19′-hexanoyloxyfucoxanthin derivatives)	Maoka et al., 2011
M. chinensis (Chinese surf clam); R. philippinarum M. petechialis	Fucoxanthin fatty acid esters	Maoka et al., 2010, 2007
	Fucoxanthinol fatty acid esters	Maoka et al., 2010, 2007
Paphia amabills P. amabillis	Amarouciaxanthin A and its ester derivatives	Maoka et al., 2008
Paphia amabills P. amabillis	C37-skeletal carotenoids	Maoka et al., 2008
Calyptogena phaseoliformis (deep-sea clam)	n-4 PUFAs	Saito, 2007
Venus verrucose (Brackish water clam)	Thio-arsenosugars	Nischwitz et al., 2006
O. rivularis	Ostrerine A	Ouyang, 2006
M. edulis	20-methyl spirolide G	Aasen et al., 2005
C. gigas	Carotenoids	Maoka et al., 2005b
C. gigas	Carotenoids	Maoka et al., 2001
M. galloprovincialis	Chlorosulfolipid	Ciminiello et al., 2004
	Polychlorinated sulfolipid	Ciminiello et al., 2002
	Oxazinins 1–3 (Bioactive alkaloids)	Ciminiello et al., 2001

**Table 7.** Some important groups of compounds extracted from ascidian and their biological activities
Class of compound	Name of the compound	Ascidian species	Biological activity	References
P388 - mouse lymphocytic leukemia cells, V-ATPase - Vacuolar-type ATPase, NCI-H460 - Lung cancer cell line.
Alkaloids	Didemnidines A and B (indole spermidine)	Didemnum sp.	Inhibitors of farnesyltransferase and phospholipase A2 enzyme without cytotoxicity	Finlayson et al., 2011
	Meridianins (brominated 3-(2-aminopyrimidine)-indoles)	Aplidium meridianum	Potential antitumor activities; Prevent cell proliferation and induce cell apoptosis; Promising kinase-inhibitory	Núñez-Pons et al., 2015
	Herdmanines A–D (nucleoside derivatives)	Herdmania momus	Inhibit the production and the expression of mRNA of pro-inflammatory cytokines; C and D show moderate suppressive effects on the production of Lipopolysaccharide induced nitricoxide	Li et al., 2012b; Li et al., 2011a
Polypeptides	Vitilevuamide (bicyclic peptide)	Didemnum cuculiferum; Polysyncranton lithostrotum	In vivo cytotoxic effect against P388 cells	Edler et al., 2002
	Diazonamides (macrocyclic peptides)	Diazona angulata	Exhibits antitumor activities; Diazonamide A is a potent chemotherapeutic agent	Cruz-Monserrate et al., 2003
	Chondromodulin-1 (glycoprotein)	Ciona savignyi	Potential antioxidant and antitumor agent; Protects H₂O₂ oxidative injury; Suppresses cell proliferation of human neuroblastoma and cervical cancer cells; Prevents angiogenesis of human umbilical vein endothelial cells	Dou et al., 2018
	CS5931	C. savignyi	Cytotoxic effects on several cancer cell; Induces apoptosis through a mitochondrial-mediated pathway	Zhao et al., 2013; Cheng et al., 2012
Polyketides	Palmerolide A (macrocyclic polyketide)	Synoicum adareanum	selective cytotoxicity toward melanoma by inhibiting V-ATPase	Noguez et al., 2011
	Mandelalides A and B (glycosylated polyketides)	Lissoclinum sp.	Potent cytotoxicity against Neuro-2a neuroblastoma cells in mouse and NCI-H460; Strong antifungicidal activity on Candida albicans	Nazari et al., 2017; Sikorska et al., 2012
	Phosphoeleganin (phosphorylated polyketide)	Sidnyum elegans	Inhibitory effect against the protein tyrosine phosphate 1B	Imperatore et al., 2016

**Table 8.** Biological activities of various natural products extracted from seaweeds
Group of compounds	Name of the compound	Seaweed source	Bioactivity	References
Polysaccharides	Fucoidans	Brown seaweeds	Anticoagulative, antioxidative, anti-inflammatory, antitumor, and antimicrobial activities	Song et al., 2012; Berteau and Mulloy, 2003
		Ascophyllum nodosum	Inhibits the invasion of breast cancer and colon adenocarcinoma cells	Haroun-Bouhedja et al., 2002
		Fucus vesiculosus	Immunomodulatory activity	Jintang et al., 2010
	Alginates	Brown seaweeds	Strong antibacterial and anti-inflammatory properties; Cholesterol-lowering and antihypertensive effects; Chelate metal ions; Inhibit the absorption of toxic substances; Play a crucial role as dietary fiber	Kim and Lee, 2008; Nishide and Uchida, 2003; Murata and Nakazoe, 2001
	Laminarin	Brown seaweeds	Antibacterial, antiviral, antitumor, and anticoagulant, and antioxidant property	Li and Kim, 2011
	Laminarin	Brown seaweeds	Reduce the systolic blood pressure, boosts the immune system, and lower the serum cholesterol	Hoffmane et al., 1995; Holdt and Kraan, 2011
	Sulfated polysaccharides	Caulerpa prolifera Sargassum filipendula	Cell proliferation inhibition	Costa et al., 2011
	Fucoxanthin	Phaeodactylum tricornutum	Anti-proliferative effect	Neumann et al., 2019
		Undaria pinnatifida	Strong radical scavenging activity	Yan et al., 1999
		Saccharina japonica Sargassum horneri	Antihypertensive activity	Sivagnanam et al., 2015
	Ulvans	Ulva lactuca Ulva rigida	Anticoagulant activity	de Carvalho et al., 2018; Adrien et al., 2019
	Ulvans	Codium fragile	Strong immunomodulatory activity	Lee et al., 2010
	Xyloarabinogalactans (Sulfated polysaccharides)	Codium fragile	Anticoagulant activity	Jurd et al., 1995
	Fucans	Padina gymnospora	Anticoagulant activity	Silva et al., 2005
Protein	Lectin	Eucheuma spp. Gracilaria sp.; Ulva sp.	Anti-inflammation, cancer metastasis, induction of apoptosis, antibacterial, and antiviral activities	Holdt and Kraan, 2011; Chojnacka et al., 2012
	Protien hydrolyzates	Gracilariopsis lemaneiformis	Antioxidant	Zhang et al., 2019b
	Dipeptides	Undaria pinnatifida	ACE inhibitory activity	Kim and Wijesekara, 2010
	Undecapeptide	Chlorella vulgaris	Antiproliferative and antioxidative activity	Sheih et al., 2010
Lipids	Phospholipids		Absorption of cholesterol, fatty acids, and other lipophilic components; Ease of digestion; Act as natural emulsifiers	Sørensen, 2009
Polyphenols	Pholorotannins (Eckol)	Ecklonia cava subsp. stolonifera	Antioxidant	Manandhar et al., 2019
	Pholorotannins	Bifurcaria bifurcata	Anti-proliferative activity	Gonçalves-Fernández et al., 2019
	Pholorotannins (Eckmaxol)	Ecklonia maxima	Neuroprotective effect	Wang et al., 2018b
	Pholorotannins (Phloroglucinol)	Eisenia bicyclis	Anticancer activity	Shibata et al., 2002
	Pholorotannins (Dioxinodehydroeckol, phlorofucofuroeckol A)	Eisenia stolonifera	Anti-allergenic effect	Shim et al., 2009
	Phlorotannins (Phlorofucofuroeckol A, dieckol, and eckol)	Ecklonia stolonifera	ACE inhibitory activity	Jung et al., 2006
	Bromophenol	Leathesia nana Rhodomela confervoides	Anticancer activity	Dong et al., 2020
		Symphyocladia latiuscula	Antidiabetic activity	Paudel et al., 2019b
		Polysiphonia morrowii	Antiviral and anti-inflammatory activity	Kim et al., 2011; Choi et al., 2018
	Flavonoids	Sargassum cristaefolium	Anticoagulant	Manggau et al., 2019
		Enteromorpha prolifera	Antidiabetic activity	Yan et al., 2019
		Caleurpa spp.	Antioxidant activity	Tanna et al., 2018
	Polyphenol extract	Ascophyllum nodosum Fucus vesiculosus	Antidiabetic activity	Zhang et al., 2007a; Lordan et al., 2013
Pigments	Pheophorbidea (Chlorophyll-a derivatives)	Enteromorpha prolifera	Strong antioxidant activity	Cho et al., 2011
Pigments	C-phycocyanin	Spirulina platensis	Anticancer activity against HeLa cells	Li et al., 2006
Others	Cyclic diterpene	Dictyota menstrualis	Antiviral activity	Cirne-Santos et al., 2019
	Meroditerpenoids (Epitaondiol and Stypodiol)	Stypopodium flabelliforme	Anti-bacterial and anticancer activities	Pereira et al., 2011
	Sesquiterpene (Zonarol)	Dictyopteris undulata	Neuroprotective effect	Shimizu et al., 2015

**Table 9.** Examples of bioactive phenolic compounds isolated from seaweeds
Class of phenolic compounds	Name of the compound	Seaweed source	Reference
Phlorotannins	Fuhalol; Phlorethols Fucophlorethols; Eckol	Sargassum fusiforme	Li et al., 2017b
	Dieckol	Ecklonia stolonifera	Yoon et al., 2013
	Octaphlorethol A	Ishige foliacea	Lee et al., 2016
	Dieckol; Phlorofucofuroeckol A; Heptafuhalol A; 8,8′-bieckol; 6,6′-bieckol	Ecklonia cava	Oh et al., 2019; Cotas et al., 2020
	Eckol; Dieckol; 8,8′-bieckol; 6,6′-bieckol; Phlorofucofuroeckol-A	Ecklonia bicyclis	Kim and Kwak, 2015
Bromophenols	5′-hydroxyisoavrainvilleol	Avrainvillea nigricans	Colon et al., 1987
	Brominated monoterpenoid quinol	Cymopolia barbata	Estrada et al., 1987
	3-bromo-4,5-dihydroxy benzoic acid methyl ester; 3-bromo-4,5 dihydroxy-benzaldehyde-bromophenols; Bis(2,3-dibromo-4,5-dihydroxybenzyl) methane	Rhodomela confervoides	Popplewell and Northcote, 2009; Wu et al., 2015
	2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether and its derivates	Scotinophara latiuscula	Paudel et al., 2019b
	5-bromo-3,4-dihydroxybenzaldehyde	Polysiphonia morrowii	Ko et al., 2019
Flavonoids	Isoflavones (daidzin or genistein)	Red seaweeds (Chondrus crispus, Porphyra/Pyropia spp.); Brown seaweeds (Sargassum muticum, Sargassum vulgare)	Cotas et al., 2020
	Flavonoid glycosides	Durvillae antarctica; Lessonia spicata; Macrocystis pyrifera	Santos et al., 2019
	Flavonoids C-glycosides	Nitell Hookeri (Green seaweed)	Markham and Porter, 1969
	Catechin; Epicatechin; Epigallocatechin; Catechin gallate; Epicatechin gallate; Epigallocatechin gallate	Acetabularia ryukyuensis Ecklonia bicyclis; Padina arborescens; Padina minor; Neopyropia yezoensis; Gelidium elegans; Portieria hornemannii	Yoshie et al., 2000
	Kaempferol; Quercetin	Caleurpa spp.	Tanna et al., 2018
	Rutin hydrate	Caleurpa corynephora; Undaria pinnatifida	Tanna et al., 2019
Phenolic acids	Coumarins	Dasycladus vermicularis	Feng et al., 2007
	Vanilic acid derivatives	Cladophora socialis	Feng et al., 2007
	Hydroxybenzoic acid; Rosmarinic acid; Quinic acid derivatives	Ascophyllum nodosum; Bifurcaria bifurcata; Fucus vesiculosus	Agregan et al., 2017
	Benzoic acid; p-hydroxybenzoic acid; Salicylic acid; Gentisic acid; Protocatechuic acid; Vanillic acid; Gallic acid; Syringic acid	Genus Gracilaria	Farvin and Jacobsen, 2013

**Table 10.** Biological activities of certain compounds derived from marine bacteria
Bacteria	Bioactive compound	Bioactivity	Reference
HCT116 - human colon cancer cell line, A549 - human lung adenocarcinoma cell line, HL-60 - human leukemia cell line, K-562 - myelogenous leukemia cell lines, HepG2 - human liver cancer cell line.
Verrucosispora sp.	Abyssomicin (Six known Abyssomicin and proximicin analogs)	Antiviral effects against the Influenza A virus	Zhang et al., 2020
Streptomyces sp.	Four 2-alkyl-4-hydroxyquinoline compounds	Antifungal activity against Candida albicans	Kim et al., 2019
Streptomyces sp. Al Dhabi-90	3-methylpyridazine n-hexadecanoic acid; Indazol-4-one; Octadecanoic acid; 3a-methyl-6-((4-methylphenyl) sul	Antibacterial activity against S. aureus, Klebsiella pneumoniae, E. coli, Pseudomonas aeruginosa, Proteus mirabilis, and Enterococcus faecium	Al-Dhabi et al., 2019
Microbacterium aurantiacum FSW-25	Exopolysaccharide	Antioxidant activities	Sran et al., 2019
Streptomyces sp. ZZ745	Bagremycins (five analogs including two new ones)	Antibacterial activity against E. coli	Zhang et al., 2018
Streptomyces sp. S2A	Pyrrolo[1–a]pyrazine-1,4-dione,hexahydro-3-(2-methylpropyl)	Antimicrobial activity against pathogenic bacteria and fungi; Inhibitory activity against α-glucosidase and α-amylase enzymes; Cytotoxic activities against different cell lines; Antioxidant activities	Siddharth and Vittal, 2018
Streptomyces sp. Bacillus sp.	Dentigerumycin E	Antiproliferative and antimetastatic activities against human carcinoma	Shin et al., 2018
Aerococcus uriaeequi HZ	Exopolysaccharides	Antioxidant activities	Wang et al., 2018a
Streptosporangium sp.	Hexaricins (pradimicin-like polyketides)	Potent antioxidant activity	Gao et al., 2018
Streptomyces sp. IMB094	Neo-actinomycins A and B (chromopeptides)	Cytotoxic activities against human cancer HCT116 and A549 cell lines; Moderate inhibitory activities against vancomycin-resistant Enterococci strains and methicillin-resistant Staphylococcus aureus	Wang et al., 2017a
Streptomyces sp. HZP-2216E	Streptopertusacin A (Alkaloid)	Antibacterial activity against methicillin-resistant Staphylococcus aureus	Zhang et al., 2017
Chromobacterium sp. HS-13-94	Chromopeptide A (depsipeptide)	Cytotoxic activity against HL-60, K-562, and Ramos cells.	Zhou et al., 2015
Saccharothrix sp.	Saccharothrixones A–D	Moderate cytotoxicity against the HepG2 cancer cell line in vitro (Saccharothrixone D)	Gan et al., 2015
Shewanella piezotolerans	Shewanellines A–C	Antitumor activity against the HL-60 cell line	Wang et al., 2014b
Serinicoccus profundi sp.	3-((6-methylpyrazin-2-yl) methyl)-1H-indole (Alkaloid)	Antibacterial activity against Staphylococcus aureus	Yang et al., 2013

**Table 11.** Biological activities of a few natural products derived from marine fungi
Fungi	Bioactive compound	Biological activity	Reference
HepG2 - human liver cancer cell line, A549 - human lung adenocarcinoma cell line, LNCaP - human prostate adenocarcinoma cells, B16F10 - murine melanoma cell line, A-375 - human melanoma cell line, CNE2 - human nasopharyngeal carcinoma cell line, LoVo - lymph node metathesis cells, 95-D – human lung cancer cells.
Aspergillus sp. LS116	Aspergillsteroid A	Antibacterial effect on aquatic pathogen Vibrio harveyi	Xu et al., 2020
Penicillium minioluteum ZZ1657	N-acetyl-L-valine conjugated drimarane sesquiterpenoids	Antimicrobial activity against methicillin-resistant S. aureus, E. coli, and C. albicans	Ma et al., 2020
Penicillium minioluteum ZZ1657	Drimane sesquiterpenoids	Antiproliferative activities against human glioma cells	Ma et al., 2020
Aspergillus sp.	Asperphenin A	Antitumoral activity against human colon cancer cells	Bae et al., 2020
Penicillium chrysogenum	Tyrosol	Anti-quorum sensing activity against P. aeruginosa and Chromobacterium violaceum	Chang et al., 2019
Penicillium sclerotiorin	Azaphilone derivative	Anti-inflammatory activity	Liu et al., 2019
Penicillium sp.	2-[(5-methyl-1,4-dioxan-2-yl) methoxy] ethanol; 2-[(2R Hydroxypropanoyl) amino] benzamide, 4- hydroxybenzandehyde	Antimicrobial activity	Le et al., 2019
Penicillium sp.	20,30-Dihydrosorbicillin	Anti-α-glucosidase activity	Le et al., 2019
Penicillium citrinum HDN-152–088	Dicitrones	Antioxidant activity	Wang et al., 2019b
Penicillium sp. IMB17-046	Trypilepyrazinol; 3b-Hydroxyergosta-8,14,24(28)-trien-7-one	Antiviral activity against HIV-1, hepatitis C virus and influenza A virus	Li et al., 2019
Penicillium sp. IMB17-046	(+)-Neocitreoviridin	Antibacterial against Helicobacter pylori; Antiviral activity against influenza A virus	Li et al., 2019
Curvularia sp. IFB-Z10	Spirocurvulaide	Cytotoxic effect on model cells of hepatomas	An et al., 2019
Chaetomium sp. NA-S01-R1	Chaephilone, chaetovirides	Antimicrobial activities; Cytotoxic effects on Hep G2 and HeLa cells	Wang et al., 2018d
Penicillium sp. ZZ901	(+)-Scleroderolide	Inhibited the growth of glioma cells; Antibacterial activity against pathogenic S. aureus and E. coli	Li et al., 2018a
Trichoderma sp. SCSIO41004	5-acetyl-2-methoxy-1,4,6-trihydroxy-anthraquinone	Antiviral activity against human Enterovirus 71	Pang et al., 2018a
Aspergillus niger AKV-MKBU	L-asparaginase	Anticancer activity	Vala et al., 2018
Truncatella angustata	Isoprenylated cyclohexanols	Antiviral effect on HIV-1 and swine-origin influenza A virus	Zhao et al., 2018b
Fusarium equiseti	(11S)-1,3,6-trihydroxi-7-(1-hydroxyethyl)-anthracene-9,10-dione	Cytotoxic activity against HepG2, A-549, and cervical (HeLa) carcinoma human cell lines	Zhao et al., 2018a
	7-acetyl-1,3,6-trihydroxyanthracene-9,10-dione	Antifungal activity against Alternaria brassicicola and Pestallozzia theae
	Alterperylenol	Antibacterial effect on Clavibacter michiganensis
Hansfordia sinuosae	Hansforesters A–M (Polyketides)	Strong inhibitory activity against numerous bacterial strains (Hansforester A)	Wu et al., 2018
Cladosporium sp. OUCMDZ-1635	Cladodionen	Cytotoxicity against several cancer cells lines	Zhu et al., 2018
Penicillium sumatrense	Sumalactones A–D; Curvularin; Dehydrocurvularin (Polyketides)	Dehydrocurvularin showed anti-inflammatory activity via inhibiting NO production	Wu et al., 2017
Penicillium chrysogenum V11	Penochalasin K	Antimicrobial activities against Rhizoctonia solani and Colletotrichum gloeosporioides; Moderate activity against a panel of cancer cell lines	Zhu et al., 2017
Penicillium sp. ZJ-SY2.	Peniphenone; Methyl peniphenone	Immunosuppressive activity	Liu et al., 2016
Chaetomium globosum	Cytoglobosins H and I (cytochalasan alkaloids) along with seven analogs	Antiproliferative activity against LNCaP and B16F10 cell lines	Zhang et al., 2016c
Penicillium citrinum	Penicitrinine A	Inhibitory effects on different tumor types, particularly on human malignant melanoma cell A-375	Liu et al., 2015a
Hansfordia sinuosae	Punctaporonins H–M (caryophyllene-type sesquiterpenoids)	Potent lipid-lowering activity by reducing the intracellular levels of triglycerides and total cholesterol (Punctaporonins K)	Wu et al., 2014
Aspergillus ochraceus Jcma1F17	6b,9a-dihydroxy-14-p nitrobenzoyl cinnamolide (nitrobenzoyl sesquiterpenoid); Insulicolide A	Anticancer effects towards a panel of cancer cell lines	Fang et al., 2014
Chondrostereum sp.	Chondrosterins A–E (triquinane-type sesquiterpenoids)	Cytotoxic activities against the cancer lines A549, CNE2, and LoVo (Chondrosterins A)	Li et al., 2012a
Penicillium sp.	Penicinoline (pyrrolyl 4-quinolinone alkaloid)	Inhibitory activity against 95-D and HepG2 cell lines	Shao et al., 2010

**Table 12.** Principles of novel techniques for extracting bioactive compounds from marine sources
Technique	Principle	References
Supercritical Fluid Extraction (Supercritical CO₂ Extraction)	Increasing pressure and temperature above their critical points while maintaining liquid and gas characteristics. Carbon dioxide (CO₂) is the frequently used solvent. Numerous combinations of temperature and pressure can be used.	Sánchez-Camargo et al., 2017
Subcritical Water Extraction	Placing liquid water for a short time (5–10 min) at high pressure (10–60 bar) and temperatures above its boiling point (100–374°C)	Zakaria and Kamal, 2016
Pulse Electric Field-Assisted Method	Disrupting cell membranes (by forming pores) using the electric field of 0.5–1.0 kV/cm field strength for 100–10,000 seconds, or 1–10 kV/cm field strength for 5–100 s. Commonly used treatment is –20 kJ/kg specific energy with 0.7–3 kV/cm electric field intensity.	Grosso et al., 2015
Microwave-Assisted Method	Due to microwaves, the moisture in the cells evaporates as the temperature rises, resulting in high pressure in the cell. It causes the rupture of cell walls and increases of porosity of the matrix	Bruno et al., 2019
Ultrasound-Assisted Method	These mechanical waves in the range of 20–1000 kHz travel through the cell matrices and make them porous. These waves create a pressure difference in the solvent and stimulate bubble formation. Then these bubbles burst, resulting in cavitation and triggering the rupture of particles. Thus, releasing bioactive chemicals into the matrix.	Ojha et al., 2020
Pressurized Liquid Extraction	High pressures (10–15 MPa), temperatures in the range of 50 to 200°C, and short time duration are used along with small volumes of non-toxic solvents (hot water can also be used). When the temperature rises, the surface tension and viscosity of liquid reduce, whereas diffusivity rises, increasing the efficiency and speed of extraction.	Otero et al., 2019
High Hydrostatic Pressure	Under high pressure (100–1000 MPa) and at a temperature of 5–35°C, cell permeability increases due to the deprotonation of charged particles, breakdown of salt bridges, and weak interactions (hydrogen bonds, electrostatic bonds, and hydrophobic bonds)	Ali et al., 2021
Membrane Separation Technologies	Compounds are isolated depending on their molecular size by semi-permeable membranes and sometimes, depending on their chemical composition by microporous membranes	Nędzarek et al., 2017
Enzymatic Extraction	Hydrolysis of compounds by using enzymes. It is a safe method, which saves time and energy. More widely used in nutraceutical applications	Ghosh et al., 2022
Fermentative Extraction	Hydrolysis of compounds by microbial fermentation. It is a better approach for deproteination, proteolysis, and demineralization	Routray et al., 2019