Promising bioactive compounds from the marine environment and their potential effects on various diseases

Akash Karthikeyan1, Abey Joseph1, Baiju G. Nair1,2
1School of Biotechnology, National Institute of Technology Calicut, Calicut, India
2Nanomedical Engineering Laboratory, Riken, Wako, Japan

Tóm tắt

The marine environment hosts a wide variety of species that have evolved to live in harsh and challenging conditions. Marine organisms are the focus of interest due to their capacity to produce biotechnologically useful compounds. They are promising biocatalysts for new and sustainable industrial processes because of their resistance to temperature, pH, salt, and contaminants, representing an opportunity for several biotechnological applications. Encouraged by the extensive and richness of the marine environment, marine organisms’ role in developing new therapeutic benefits is heading as an arable field. There is currently much interest in biologically active compounds derived from natural resources, especially compounds that can efficiently act on molecular targets, which are involved in various diseases. Studies are focused on bacteria and fungi, isolated from sediments, seawater, fish, algae, and most marine invertebrates such as sponges, mollusks, tunicates, coelenterates, and crustaceans. In addition to marine macro-organisms, such as sponges, algae, or corals, marine bacteria and fungi have been shown to produce novel secondary metabolites (SMs) with specific and intricate chemical structures that may hold the key to the production of novel drugs or leads. The marine environment is known as a rich source of chemical structures with numerous beneficial health effects. Presently, several lines of studies have provided insight into biological activities and neuroprotective effects of marine algae, including antioxidant, anti-neuroinflammatory, cholinesterase inhibitory activity, and neuronal death inhibition. The application of marine-derived bioactive compounds has gained importance because of their therapeutic uses in several diseases. Marine natural products (MNPs) display various pharmaceutically significant bioactivities, including antibiotic, antiviral, neurodegenerative, anticancer, or anti-inflammatory properties. The present review focuses on the importance of critical marine bioactive compounds and their role in different diseases and highlights their possible contribution to humanity.

Tài liệu tham khảo

Bollmann M (2010) World ocean review: living with the oceans Subramani R, Aalbersberg W (2013) Culturable rare Actinomycetes: diversity, isolation and marine natural product discovery. Appl Microbiol Biotechnol 97:9291–9321 Ramirez-Llodra E, Tyler PA, Baker MC, Bergstad OA, Clark MR, Escobar E, Levin LA, Menot L, Rowden AA, Smith CR (2011) Man and the last great wilderness: human impact on the deep sea. PLoS One 6:e22588 Newman DJ, Cragg GM (2018) Marine Natural Products with Pharmacological Properties. In Chemical Ecology. CRC Press, pp. 1–25 Atlas RM (1998) Microbial ecology: fundamentals and applications. Pearson Education India Pinnaka AK, Tanuku NRS (2019) Marine microbial diversity for sustainable development, microbial diversity in ecosystem sustainability and biotechnological applications. Springer, pp 117–158 Mahapatra GP, Raman S, Nayak S, Gouda S, Das G, Patra JK (2020) Metagenomics approaches in discovery and development of new bioactive compounds from marine Actinomycetes. Curr Microbiol 77:645–656 Sekurova ON, Schneider O, Zotchev SB (2019) Novel bioactive natural products from bacteria via bioprospecting, genome mining and metabolic engineering. Microb Biotechnol 12:828–844 Haefner B (2003) Drugs from the deep: marine natural products as drug candidates. Drug Discov Today 8:536–544 Lahlou M (2013) The success of natural products in drug discovery. Pharmacol Pharm 04:17–31 Yarza P, Yilmaz P, Pruesse E, Glockner FO, Ludwig W, Schleifer KH, Whitman WB, Euzeby J, Amann R, Rossello-Mora R (2014) Uniting the classification of cultured and uncultured bacteria and archaea using 16S rRNA gene sequences. Nat Rev Microbiol 12:635–645 Dalmaso GZ, Ferreira D, Vermelho AB (2015) Marine extremophiles: a source of hydrolases for biotechnological applications. Mar Drugs 13:1925–1965 Trincone A (2010) Potential biocatalysts originating from sea environments. J Mol Catal B Enzym 66:241–256 Suleria HAR, Gobe G, Masci P, Osborne SA (2016) Marine bioactive compounds and health promoting perspectives; innovation pathways for drug discovery. Trends Food Sci Technol 50:44–55 Igarashi Y, Ogura H, Furihata K, Oku N, Indananda C, Thamchaipenet A (2011) Maklamicin, an antibacterial polyketide from an endophytic Micromonospora sp. J Nat Prod 74:670–674 Igarashi Y, Iida T, Oku N, Watanabe H, Furihata K, Miyanouchi K (2012) Nomimicin, a new spirotetronate-class polyketide from an actinomycete of the genus Actinomadura. J Antibiot (Tokyo) 65:355–359 Niu S, Li S, Chen Y, Tian X, Zhang H, Zhang G, Zhang W, Yang X, Zhang S, Ju J, Zhang C (2011) Lobophorins E and F, new spirotetronate antibiotics from a South China Sea-derived Streptomyces sp. SCSIO 01127. J Antibiot (Tokyo) 64:711–716 Chen C, Wang J, Guo H, Hou W, Yang N, Ren B, Liu M, Dai H, Liu X, Song F, Zhang L (2013) Three antimycobacterial metabolites identified from a marine-derived Streptomyces sp. MS100061. Appl Microbiol Biotechnol 97:3885–3892 Rateb ME, Ebel R, Jaspars M (2018) Natural product diversity of actinobacteria in the Atacama Desert. Antonie Van Leeuwenhoek 111:1467–1477 Abdelkader MSA, Philippon T, Asenjo JA, Bull AT, Goodfellow M, Ebel R, Jaspars M, Rateb ME (2018) Asenjonamides A-C, antibacterial metabolites isolated from Streptomyces asenjonii strain KNN 42.f from an extreme-hyper arid Atacama Desert soil. J Antibiot (Tokyo) 71:425–431 Hou J, Liu P, Qu H, Fu P, Wang Y, Wang Z, Li Y, Teng X, Zhu W (2012) Gilvocarcin HE: a new polyketide glycoside from Streptomyces sp. J Antibiot (Tokyo) 65:523–526 Lü Y, Shao M, Wang Y, Qian S, Wang M, Wang Y, Li X, Bao Y, Deng C, Yue C, Liu D, Liu N, Liu M, Huang Y, Chen Z, Hu Y (2017) Zunyimycins B and C, New chloroanthrabenzoxocinones antibiotics against methicillin-resistant Staphylococcus aureus and Enterococci from Streptomyces sp. FJS31-2. Molecules (Basel, Switzerland) 22:251 Qin Z, Munnoch JT, Devine R, Holmes NA, Seipke RF, Wilkinson KA, Wilkinson B, Hutchings MI (2017) Formicamycins, antibacterial polyketides produced by Streptomyces formicae isolated from African Tetraponera plant-ants. Chem Sci 8:3218–3227 Cruz JC, Maffioli SI, Bernasconi A, Brunati C, Gaspari E, Sosio M, Wellington E, Donadio S (2017) Allocyclinones, hyperchlorinated angucyclinones from Actinoallomurus. J Antibiot (Tokyo) 70:73–78 Rathod BB, Korasapati R, Sripadi P, Reddy Shetty P (2018) Novel actinomycin group compound from newly isolated Streptomyces sp. RAB12: isolation, characterization, and evaluation of antimicrobial potential. Appl Microbiol Biotechnol 102:1241–1250 Cheng C, Othman EM, Reimer A, Grüne M, Kozjak-Pavlovic V, Stopper H, Hentschel U, Abdelmohsen UR (2016) Ageloline A, new antioxidant and antichlamydial quinolone from the marine sponge-derived bacterium Streptomyces sp. SBT345. Tetrahedron Lett 57:2786–2789 Loureiro DRP, Soares JX, Costa JC, Magalhaes AF, Azevedo CMG, Pinto MMM, Afonso CMM (2019) Structures, activities and drug-likeness of anti-infective xanthone derivatives isolated from the marine environment: a review. Molecules 24(2):243 Liu LL, Xu Y, Han Z, Li YX, Lu L, Lai PY, Zhong JL, Guo XR, Zhang XX, Qian PY (2012) Four new antibacterial xanthones from the marine-derived actinomycetes Streptomyces caelestis. Mar Drugs 10:2571–2583 Mahajan G, Thomas B, Parab R, Patel ZE, Kuldharan S, Yemparala V, Mishra PD, Ranadive P, D’Souza L, Pari K, Sivaramkrishnan H (2013) In vitro and in vivo activities of antibiotic PM181104. Antimicrob Agents Chemother 57:5315–5319 Wu Z, Li S, Li J, Chen Y, Saurav K, Zhang Q, Zhang H, Zhang W, Zhang W, Zhang S, Zhang C (2013) Antibacterial and cytotoxic new napyradiomycins from the marine-derived Streptomyces sp. SCSIO 10428. Mar Drugs 11:2113–2125 Shin B, Kim BY, Cho E, Oh KB, Shin J, Goodfellow M, Oh DC (2016) Actinomadurol, an antibacterial norditerpenoid from a rare actinomycete, Actinomadura sp. KC 191. J Nat Prod 79:1886–1890 Manam RR, Teisan S, White DJ, Nicholson B, Grodberg J, Neuteboom ST, Lam KS, Mosca DA, Lloyd GK, Potts BC (2005) Lajollamycin, a nitro-tetraene spiro-beta-lactone-gamma-lactam antibiotic from the marine actinomycete Streptomyces nodosus. J Nat Prod 68:240–243 Um S, Choi TJ, Kim H, Kim BY, Kim SH, Lee SK, Oh KB, Shin J, Oh DC (2013) Ohmyungsamycins A and B: cytotoxic and antimicrobial cyclic peptides produced by Streptomyces sp. from a volcanic island. J Org Chem 78:12321–12329 Sun P, Maloney KN, Nam SJ, Haste NM, Raju R, Aalbersberg W, Jensen PR, Nizet V, Hensler ME, Fenical W (2011) Fijimycins A-C, three antibacterial etamycin-class depsipeptides from a marine-derived Streptomyces sp. Bioorg Med Chem 19:6557–6562 Shazleen AA (2017) Dissertation. Discovery of novel rare actinobacteria isolated from mangrove environments in the east coast of Peninsular Malaysia Veena S, Swetha D, Karthik L, Bhaskara Rao K (2016) Assessment of anti-typhoid and antioxidant activity of marine actinobacteria isolated from Chennai marine sediments. Der Pharm Lett 8:166–172 Vijayakumar R, Muthukumar C, Thajuddin N, Panneerselvam A, Saravanamuthu R (2007) Studies on the diversity of actinomycetes in the Palk Strait region of Bay of Bengal, India. Actinomycetologica 21(2):0712050027 Avilala J, Kumar AP, Viswanath B, Gopal DVRS, Narasimha G (2018) Antiviral and larvicidal properties of novel bioactive compounds produced from marine actinomycetes. Russ J Mar Biol 44:424–428 Saha S, Dhanasekaran D, Shanmugapriya S, Latha S (2013) Nocardiopsis sp. SD5: a potent feather degrading rare actinobacterium isolated from feather waste in Tamil Nadu, India. J Basic Microbiol 53:608–616 Kirst HA (2010) The spinosyn family of insecticides: realizing the potential of natural products research. J Antibiot 63(3):101–111 Dhanasekaran D, Sakthi V, Thajuddin N, Panneerselvam A (2010) Preliminary evaluation of anopheles mosquito larvicidal efficacy of mangrove actinobacteria. Int J Appl Biol Pharm 1(2):374–81 Vo TS, Ngo DH, Kang KH, Jung WK, Kim SK (2015) The beneficial properties of marine polysaccharides in alleviation of allergic responses. Mol Nutr Food Res 59:129–138 Cardoso ML, Xavier CA, Bezerra MB, Paiva AO, Carvalho MF, Benevides NM, Rocha FA, Leite EL (2010) Assessment of zymosan-induced leukocyte influx in a rat model using sulfated polysaccharides. Planta Med 76:113–119 Matsui MS, Muizzuddin N, Arad S, Marenus K (2003) Sulfated polysaccharides from red microalgae have antiinflammatory properties in vitro and in vivo. Appl Biochem Biotechnol 104:13–22 Medeiros VP, Queiroz KCS, Cardoso ML, Monteiro GRG, Oliveira FW, Chavante SF, Guimaraes LA, Rocha HAO, Leite EL (2008) Sulfated galactofucan from Lobophora variegata: anticoagulant and anti-inflammatory properties. Biochem (Moscow) 73:1018–1024 De Jesus Raposo MS, De Morais AM, De Morais RM (2015) Marine polysaccharides from algae with potential biomedical applications. Mar Drugs 13:2967–3028 Cheung RC, Wong JH, Pan W, Chan YS, Yin C, Dan X, Ng TB (2015) Marine lectins and their medicinal applications. Appl Microbiol Biotechnol 99:3755–3773 Da Conceicao Rivanor RL, Chaves HV, Do Val DR, De Freitas AR, Lemos JC, Rodrigues JA, Pereira KM, De Araujo IW, Bezerra MM, Benevides NM (2014) A lectin from the green seaweed Caulerpa cupressoides reduces mechanical hyper-nociception and inflammation in the rat temporomandibular joint during zymosan-induced arthritis. Int Immunopharmacol 21:34–43 Sepcic K, Marcel V, Klaebe A, Turk T, Suput D, Fournier D (1998) Inhibition of acetylcholinesterase by an alkylpyridinium polymer from the marine sponge, Reniera sarai. Biochim Biophys Acta 1387:217–225 Tan L, Guo S, Ma F, Chang, Gómez-Betancur I (2018) In vitro inhibition of acetylcholinesterase, alphaglucosidase, and xanthine oxidase by bacteria extracts from coral reef in Hainan, South China Sea. J Mar Sci Eng 6(2):33 Mitchell SS, Nicholson B, Teisan S, Lam KS, Potts BC (2004) Aureoverticillactam, a novel 22-atom macrocyclic lactam from the marine actinomycete Streptomyces aureoverticillatus. J Nat Prod 67:1400–1402 Stritzke K, Schulz S, Laatsch H, Helmke E, Beil W (2004) Novel caprolactones from a marine streptomycete. J Nat Prod 67:395–401 Li F, Maskey RP, Qin S, Sattler I, Fiebig H, Maier A, Zeeck A, Laatsch H (2005) Chinikomycins A and B: isolation, structure elucidation, and biological activity of novel antibiotics from a marine Streptomyces sp. isolate M045. J Nat Prod 68:349–353 Malet-Cascon L, Romero F, Espliego-Vazquez F, Gravalos D, Fernandez-Puentes JL (2003) IB-00208, a new cytotoxic polycyclic xanthone produced by a marine-derived Actinomadura. I. Isolation of the strain, taxonomy and biological activities. J Antibiot (Tokyo) 56:219–225 Beer LL, Moore BS (2007) Biosynthetic convergence of salinosporamides A and B in the marine actinomycete Salinispora tropica. Org Lett 9:845–848 Ganesan S, Velsamy G, Sivasudha T, Manoharan N (2013) MALDI-TOF mass spectrum profiling, antibacterial and anticancer activity of marine Streptomyces fradiae BDMS1. World J Pharm Pharm Sci 2:5148–5165 Leet JE, Schroeder DR, Golik J, Matson JA, Doyle TW, Lam KS, Hill SE, Lee MS, Whitney JL, Krishnan BS (1996) Himastatin, a new antitumor antibiotic from Streptomyces hygroscopicus. III. Structural elucidation. J Antibiot (Tokyo) 49:299–311 Asolkar RN, Jensen PR, Kauffman CA, Fenical W (2006) Daryamides A-C, weakly cytotoxic polyketides from a marine-derived actinomycete of the genus Streptomyces strain CNQ-085. J Nat Prod 69:1756–1759 Kim SK, Hoang VL, Kim MM (2006) Bioactive compounds derived from marine bacteria: anti-cancer activity. J Mar Biosci Biotechnol 1:232–242 Martin GD, Tan LT, Jensen PR, Dimayuga RE, Fairchild CR, Raventos-Suarez C, Fenical W (2007) Marmycins A and B, cytotoxic pentacyclic C-glycosides from a marine sediment-derived actinomycete related to the genus Streptomyces. J Nat Prod 70:1406–1409 Smith WC, Xiang L, Shen B (2000) Genetic localization and molecular characterization of the nonS gene required for macrotetrolide biosynthesis in Streptomyces griseus DSM40695. Antimicrob Agents Chemother 44:1809–1817 Butler MS (2008) Natural products to drugs: natural product-derived compounds in clinical trials. Nat Prod Rep 25:475–516 Takahashi A, Kurasawa S, Ikeda D, Okami Y, Takeuchi T (1989) Altemicidin, a new acaricidal and antitumor substance. J Antibiot 42:1556–1561 Shin HJ, Jeong HS, Lee HS, Park SK, Kim HM, Kwon HJ (2007) Isolation and structure determination of streptochlorin, an antiproliferative agent from a marine-derived Streptomyces sp. 04DH110. J Microbiol Biotechnol 17:1403–1406 Boonlarppradab C, Kauffman CA, Jensen PR, Fenical W (2008) Marineosins A and B, cytotoxic spiroaminals from a marine-derived actinomycete. Org Lett 10:5505–5508 Pan E, Oswald NW, Legako AG, Life JM, Posner BA, Macmillan JB (2013) Precursor-directed generation of amidine containing ammosamide analogs: ammosamides E-P. Chem Sci 4:482–488 Losada AA, Cano-Prieto C, Garcia-Salcedo R, Brana AF, Mendez C, Salas JA, Olano C (2017) Caboxamycin biosynthesis pathway and identification of novel benzoxazoles produced by cross-talk in Streptomyces sp. NTK 937. Microb Biotechnol 10:873–885 Malloy KL, Choi H, Fiorilla C, Valeriote FA, Matainaho T, Gerwick WH (2012) Hoiamide D, a marine cyanobacteria-derived inhibitor of p53/MDM2 interaction. Bioorg Med Chem Lett 22:683–688 Kato H, Nehira T, Matsuo K, Kawabata T, Kobashigawa Y, Morioka H, Losung F, Mangindaan RE, De Voogd NJ, Yokosawa H (2015) Niphateolide A: isolation from the marine sponge Niphates olemda and determination of its absolute configuration by an ECD analysis. Tetrahedron 71:6956–6960 Tsukamoto S, Yoshida T, Hosono H, Ohta T, Yokosawa H (2006) Hexylitaconic acid: a new inhibitor of p53–HDM2 interaction isolated from a marine-derived fungus, Arthrinium sp. Bioorg Med Chem Lett 16:69–71 Clement JA, Kitagaki J, Yang Y, Saucedo CJ, O’Keefe BR, Weissman AM, McKee TC, McMahon JB (2008) Discovery of new pyridoacridine alkaloids from Lissoclinum cf. badium that inhibit the ubiquitin ligase activity of Hdm2 and stabilize p53. Bioorg Med Chem 16:10022–10028 Tsukamoto S, Hirota H, Imachi M, Fujimuro M, Onuki H, Ohta T, Yokosawa H (2005) Himeic acid A: a new ubiquitin-activating enzyme inhibitor isolated from a marine-derived fungus, Aspergillus sp. Bioorg Med Chem Lett 15:191–194 Tsukamoto S, Yamashita K, Tane K, Kizu R, Ohta T, Matsunaga S, Fusetani N, Kawahara H, Yokosawa H, Bulletin P (2004) Girolline, an antitumor compound isolated from a sponge, induces G2/M cell cycle arrest and accumulation of polyubiquitinated p53. Biol Pharm Bul 27:699–701 Tsukamoto S, Takeuchi T, Rotinsulu H, Mangindaan RE, Van Soest RW, Ukai K, Kobayashi H, Namikoshi M, Ohta T, Yokosawa H (2008) Leucettamol A: a new inhibitor of Ubc13-Uev1A interaction isolated from a marine sponge, Leucetta aff. Microrhaphis Bioorg Med Chem Lett 18:6319–6320 Gunasekera SP, McCarthy PJ, Kelly-Borges M, Lobkovsky E, Clardy J (1996) Dysidiolide: a novel protein phosphatase inhibitor from the Caribbean sponge Dysidea etheria de Laubenfels. J Am Chem Soc 118:8759–8760 Nagle DG, Zhou YD, Mora FD, Mohammed KA, Kim YP (2004) Mechanism targeted discovery of antitumor marine natural products. Curr Med Chem 11:1725–1756 Loukaci S, Le Saout I, Samadi M, Leclerc S, Damiens E, Meijer L, Debitus C, Guyot M (2001) Coscinosulfate, a CDC25 phosphatase inhibitor from the sponge Coscinoderma mathewsi. Bioorg Med Chem 9:3049–3054 Skropeta D, Pastro N, Zivanovic A (2011) Kinase inhibitors from marine sponges Mar. Drugs 9:2131–2154 Cherigo L, Lopez D, Martinez-Luis S (2015) Marine natural products as breast cancer resistance protein inhibitors. Mar Drugs 13:2010–2029 Wang R, Zhang Q, Peng X, Zhou C, Zhong Y, Chen X, Qiu Y, Jin M, Gong M, Kong D (2016) Stellettin B induces G1 arrest, apoptosis and autophagy in human non-small cell lung cancer A549 cells via blocking PI3K/Akt/mTOR pathway. Sci Rep 6:1–10 Bister B, Bischoff, Strobele M, Riedlinger J, Reicke A, Wolter F, Bull AT, Zahner H, Fiedler HP, Sussmuth RD (2004) Abyssomicin C-A polycyclic antibiotic from a marine Verrucosispora strain as an inhibitor of the p-aminobenzoic acid/tetrahydrofolate biosynthesis pathway. Angew Chem Int Ed Engl 43:2574–2576 Bruntner C, Binder T, Pathom-aree W, Goodfellow M, Bull AT, Potterat O, Puder C, Horer S, Schmid A, Bolek W, Wagner K, Mihm G, Fiedler HP (2005) Frigocyclinone, a novel angucyclinone antibiotic produced by a Streptomyces griseus strain from Antarctica. J Antibiot (Tokyo) 58:346–349 Lu Y, Dong X, Liu S, Bie X (2009) Characterization and identification of a novel marine Streptomyces sp. produced antibacterial substance. Mar Biotechnol (NY) 11:717–724 Maskey RP, Helmke E, Kayser O, Fiebig HH, Maier A, Busche A, Laatsch H (2004) Anti-cancer and antibacterial trioxacarcins with high anti-malaria activity from a marine Streptomycete and their absolute stereochemistry. J Antibiot 57:771–779 Flora DO, Adeyemi AI, George WP (2015) Himalomycin A and cycloheximide-producing marine actinomycete from Lagos Lagoon soil sediment. J Coast Life Med 3:361–365 Phan LY, Jian T, Chen Z, Qiu YL, Wang Z, Beach T, Polemeropoulos A, Or YS (2004) Synthesis and antibacterial activity of a novel class of 4’-substituted 16-membered ring macrolides derived from tylosin. J Med Chem 47:2965–2968 Igarashi M, Sawa R, Yamasaki M, Hayashi C, Umekita M, Hatano M, Fujiwara T, Mizumoto K, Nomoto A (2017) Kribellosides, novel RNA 5’-triphosphatase inhibitors from the rare actinomycete Kribbella sp. MI481-42F6. J Antibiot (Tokyo) 70:582–589 Brana AF, Sarmiento-Vizcaino A, Osset M, Perez-Victoria I, Martin J, De Pedro N, De la Cruz M, Diaz C, Vicente F, Reyes F, Garcia LA, Blanco G (2017) Lobophorin K, a new natural product with cytotoxic activity produced by Streptomyces sp. M-207 associated with the deep-sea coral Lophelia pertusa. Mar Drugs 15(5):144 Moon K, Chung B, Shin Y, Lee SK, Oh KB, Shin J, Oh DC (2015) Discovery of new bioactive secondary metabolites from bacteria in extreme habitats. Planta Med 81(11):PT24 Rao M, Wei W, Ge M, Chen D, Sheng X (2013) A new antibacterial lipopeptide found by UPLC-MS from an actinomycete Streptomyces sp. HCCB10043. Nat Prod Res 27:2190–2195 Ramalingam V, Varunkumar K, Ravikumar V, Rajaram R (2018) p53 mediated transcriptional regulation of long non-coding RNA by 1-hydroxy-1-norresistomycin triggers intrinsic apoptosis in adenocarcinoma lung cancer. Chem Biol Interact 287:1–12 Yu Y, Wu J, Lei F, Chen L, Wan W, Hai L, Guan M, Wu Y (2013) Design, synthesis and anticancer activity evaluation of diazepinomicin derivatives. Lett Drug Des Disc 10:369–373 Jensen PR, Williams PG, Oh DC, Zeigler L, Fenical W (2007) Species-specific secondary metabolite production in marine actinomycetes of the genus Salinispora. Appl Environ Microbiol 73:1146–1152 Itoh T, Kinoshita M, Aoki S, Kobayashi M (2003) Komodoquinone A, a novel neuritogenic anthracycline, from marine Streptomyces sp. KS3. J Nat Prod 66:1373–1377 Oja T, San Martin Galindo P, Taguchi T, Manner S, Vuorela PM, Ichinose K, Metsa-Ketela M, Fallarero A (2015) Effective antibiofilm polyketides against Staphylococcus aureus from the pyranonaphthoquinone biosynthetic pathways of Streptomyces species. Antimicrob Agents Chemother 59:6046–6052 Meijer L, Thunnissen AM, White A, Garnier M, Nikolic M, Tsai L, Walter J, Cleverley K, Salinas P, Wu Y, Biernat J (2000) Inhibition of cyclin-dependent kinases, GSK-3β and CK1 by hymenialdisine, a marine sponge constituent. Chem Biol 7:51–63 Barry CE III, Slayden RA, Sampson AE, Lee RE (2000) Use of genomics and combinatorial chemistry in the development of new antimycobacterial drugs. Biochem Pharm 59:221–231 Copp BR (2003) Antimycobacterial natural products. Nat Prod Rep 20:535–557 Tiberi S, Munoz-Torrico M, Duarte R, Dalcolmo M, D’Ambrosio L, Migliori GB (2018) New drugs and perspectives for new anti-tuberculosis regimens. Pulmonology 24:86–98 Patridge E, Gareiss P, Kinch MS, Hoyer D (2016) An analysis of FDA-approved drugs: natural products and their derivatives. Drug Discov Today 21:204–207 Leiros M, Alonso E, Rateb ME, Ebel R, Jaspars M, Alfonso A, Botana LM (2015) The Streptomyces metabolite anhydroexfoliamycin ameliorates hallmarks of Alzheimer’s disease in vitro and in vivo. Neuroscience 305:26–35 Adsersen A, Gauguin B, Gudiksen L, Jager AK (2006) Screening of plants used in Danish folk medicine to treat memory dysfunction for acetylcholinesterase inhibitory activity. J Ethnopharmacol 104:418–422 Dohi S, Terasaki M, Makino M (2009) Acetylcholinesterase inhibitory activity and chemical composition of commercial essential oils. J Agric Food Chem 57:4313–4318 Chang CJ, Floss HG, Soong P, Chang CT (1975) Identity of the antitumor antibiotic litmomycin with granaticin A. J Antibiot (Tokyo) 28:156 Elson AL, Box SJ, Gilpin ML (1988) New quinone antibiotics of the granaticin type, isolated from Streptomyces lateritius. I. Production, isolation and properties. J Antibiot (Tokyo) 41:570–572 Almasi F, Mohammadipanah F, Adhami HR, Hamedi J (2018) Introduction of marine-derived Streptomyces sp. UTMC 1334 as a source of pyrrole derivatives with anti-acetylcholinesterase activity. J Appl Microbiol 125:1370–1382 Karran E, Mercken M, De Strooper B (2011) The amyloid cascade hypothesis for Alzheimer’s disease: an appraisal for the development of therapeutics. Nat Rev Drug Discov 10:698–712 Sharma V, Lansdell TA, Jin G, Tepe JJ (2004) Inhibition of cytokine production by hymenialdisine derivatives. J Med Chem 47:3700–3703 Huang C, Zhang Z, Cui W (2019) Marine-derived natural compounds for the treatment of Parkinson’s disease. Mar Drugs 17(4):221 Nikapitiya C (2012) Bioactive secondary metabolites from marine microbes for drug discovery. Adv Food Nutr Res 65:363–387 Monciardini P, Iorio M, Maffioli S, Sosio M, Donadio S (2014) Discovering new bioactive molecules from microbial sources. Microb Biotechnol 7:209–220 Koppula S, Kumar H, More SV, Kim BW, Kim IS, Choi DK (2012) Recent advances on the neuroprotective potential of antioxidants in experimental models of Parkinson’s disease. Int J Mol Sci 13:10608–10629 Mena MA, Casarejos MJ, Solano R, Rodriguez-Navarro JA, Gomez A, Rodal I, Medina M, De Yebenes JG (2009) NP7 protects from cell death induced by oxidative stress in neuronal and glial midbrain cultures from parkin null mice. FEBS Lett 583:168–174 Takeuchi T, Ogawa K, Iinuma H, Suda H, Ukita K (1973) Monoamine oxidase inhibitors isolated from fermented broths. J Antibiot (Tokyo) 26:162–167 Lee HW, Choi H, Nam SJ, Fenical W, Kim H (2017) Potent inhibition of monoamine oxidase B by a piloquinone from marine-derived Streptomyces sp. CNQ-027. J Microbiol Biotechnol 27:785–790 Moore BS, Trischman JA, Seng D, Kho D, Jensen PR, Fenical W (1999) Salinamides, antiinflammatory depsipeptides from a marine streptomycete. J Org Chem 64:1145–1150 Renner MK, Shen YC, Cheng XC, Jensen PR, Frankmoelle W, Kauffman CA, Fenical W, Lobkovsky E, Clardy J (1999) Cyclomarins A−C, new antiinflammatory cyclic peptides produced by a marine bacterium (Streptomyces sp.). J Am Chem Soc 121:11273–11276 Wen SJ, Hu TS, Yao ZJ (2005) Macrocyclization studies and total synthesis of cyclomarin C, an anti-inflammatory marine cyclopeptide. Tetrahedron 61:4931–4938 Pietra F (1997) Secondary metabolites from marine microorganisms: bacteria, protozoa, algae and fungi. Achievements and prospects. Nat Prod Rep 14:453–464 Gomathi A, Gothandam KM (2016) Ocean dwelling actinobacteria as source of antitumor compounds. Braz Arch Biol Technol 59 Kwon HC, Kauffman CA, Jensen PR, Fenical W (2006) Marinomycins A−D, antitumor-antibiotics of a new structure class from a marine actinomycete of the recently discovered genus “Marinispora”. J Am Chem Soc 128:1622–1632 Wu SJ, Fotso S, Li F, Qin S, Laatsch H (2007) Amorphane sesquiterpenes from a marine Streptomyces sp. J Nat Prod 70:304–306 Asolkar RN, Maskey RP, Helmke E, Laatsch H (2002) Chalcomycin B, a new macrolide antibiotic from the marine isolate Streptomyces sp. B7064. J Antibiot (Tokyo) 55:893–898 Gupta RS, Murray W, Gupta R (1988) Cross resistance pattern towards anticancer drugs of a human carcinoma multidrug-resistant cell line. Br J Cancer 58:441–447 Jeong SY, Shin HJ, Kim TS, Lee HS, Park SK, Kim HM (2006) Streptokordin, a new cytotoxic compound of the methylpyridine class from a marine-derived Streptomyces sp. KORDI-3238. J Antibiot (Tokyo) 59:234–240 Borrel MN, Pereira E, Fiallo M, Garnier-Suillerot A (1994) Mobile ionophores are a novel class of P-glycoprotein inhibitors. The effects of ionophores on 4’-O-tetrahydropyranyl-adriamycin incorporation in K562 drug-resistant cells. Eur J Biochem 223:125–133 Xu Z, Jakobi K, Welzel K, Hertweck C (2005) Biosynthesis of the antitumor agent chartreusin involves the oxidative rearrangement of an anthracyclic polyketide. Chem Biol 12:579–588 Lorico A, Long BH (1993) Biochemical characterisation of elsamicin and other coumarin-related antitumour agents as potent inhibitors of human topoisomerase II. Eur J Can 29:1985–1991 Hughes CC, MacMillan JB, Gaudencio SP, Jensen PR, Fenical W (2009) The ammosamides: structures of cell cycle modulators from a marine-derived Streptomyces species. Angew Chem Int Ed Engl 48:725–727 Liu R, Cui CB, Duan L, Gu QQ, Zhu WM (2005) Potent in vitro anticancer activity of metacycloprodigiosin and undecylprodigiosin from a sponge-derived actinomycete Saccharopolyspora sp. nov. Arch Pharm Res 28:1341–1344 Wasserman H, Keith D, Rodgers G (1976) The structure of metacycloprodigiosin. Tetrahedron 32:1855–1861 Perez-Tomas R, Montaner B, Llagostera E, Soto-Cerrato V (2003) The prodigiosins, proapoptotic drugs with anticancer properties. Biochem Pharmacol 66:1447–1452 Mi Y, Zhang J, He S, Yan X (2017) New peptides isolated from marine cyanobacteria, an overview over the past decade. Mar Drugs 15:132 Schneider K, Keller S, Wolter FE, Röglin L, Beil W, Seitz O, Nicholson G, Bruntner C, Riedlinger J, Fiedler HP (2008) Proximicins A, B, and C—antitumor furan analogues of netropsin from the marine actinomycete Verrucosispora induce upregulation of p53 and the cyclin kinase inhibitor p21. Angew Chem Int Ed Engl 47:3258–3261 Zhang W, Che Q, Tan H, Qi X, Li J, Li D, Gu Q, Zhu T, Liu M (2017) Marine Streptomyces sp. derived antimycin analogues suppress HeLa cells via depletion HPV E6/E7 mediated by ROS-dependent ubiquitin–proteasome system. Sci Rep 7:1–14 Zhang JY, Tao LY, Liang YJ, Yan YY, Dai CL, Xia XK, She ZG, Lin YC, Fu LW (2009) Secalonic acid D induced leukemia cell apoptosis and cell cycle arrest of G1 with involvement of GSK-3β/β-catenin/c-Myc pathway. Cell Cycle 8:2444–2450 Barbieri F, Thellung S, Würth R, Gatto F, Corsaro A, Villa V, Nizzari M, Albertelli M, Ferone D, Florio T (2014) Emerging targets in pituitary adenomas: role of the CXCL12/CXCR4-R7 system. Int J Endocrinol 2014:753524 Vitale RM, Gatti M, Carbone M, Barbieri F, Felicità V, Gavagnin M, Florio T, Amodeo P (2013) Minimalist hybrid ligand/receptor-based pharmacophore model for CXCR4 applied to a small-library of marine natural products led to the identification of phidianidine a as a new CXCR4 ligand exhibiting antagonist activity. Chem Biol 8:2762–2770 Kwak JY (2014) Fucoidan as a marine anticancer agent in preclinical development. Mar Drugs 12:851–870 Sharma A, Nandi S (2020) Abnormal signal transduction via over-expression of Pim-1 regulated senescence, cell cycle, apoptosis and metastatic invasion: novel anticancer targets and their potent inhibitors from marine sources. Curr Signal Trans Ther 15(1):3–11 Rinehart KL, Gloer JB, Hughes RG, Renis HE, McGovren JP, Swynenberg EB, Stringfellow DA, Kuentzel SL, Li LH (1981) Didemnins: antiviral and antitumor depsipeptides from a Caribbean tunicate. Science 212:933–935 Canonico PG, Pannier WL, Huggins JW, Rienehart KL (1982) Inhibition of RNA viruses in vitro and in Rift Valley fever-infected mice by didemnins A and B. Antimicrob Agents Chemother 22:696–697 Reuschl AK, Thorne LG, Zuliani-Alvarez L, Bouhaddou M, Obernier K, Soucheray M, Turner J, Fabius JM, Nguyen GT, Swaney DL, Rosales R (2021) Host-directed therapies against early-lineage SARS-CoV-2 retain efficacy against B. 1.1. 7 variant. BioRxiv González-Cano R, Ruiz-Cantero MC, Santos-Caballero M, Gómez-Navas C, Tejada MA, Nieto FR (2021) Tetrodotoxin, a potential drug for neuropathic and cancer pain relief? Toxins 13:483 Kitagawa H, Takenouchi T, Azuma R, Wesnes KA, Kramer WG, Clody DE, Burnett AL (2003) Safety, pharmacokinetics, and effects on cognitive function of multiple doses of GTS-21 in healthy, male volunteers. Neuropsychopharmacology 28:542–551 Teixidó C, Arguelaguet E, Pons B, Aracil M, Jimeno J, Somoza R, Marés R, Ramón y Cajal S, Hernández-Losa J (2012) ErbB3 expression predicts sensitivity to elisidepsin treatment: in vitro synergism with cisplatin, paclitaxel and gemcitabine in lung, breast and colon cancer cell lines. Int J Oncol 41:317–324 Xue C, Liang F, Mahmood R, Vuolo M, Wyckoff J, Qian H, Tsai KL, Kim M, Locker J, Zhang ZY, Segall JE (2006) ErbB3-dependent motility and intravasation in breast cancer metastasis. Cancer Res 66:1418–1426 Correa H, Aristizabal F, Duque C, Kerr R (2011) Cytotoxic and antimicrobial activity of pseudopterosins and seco-pseudopterosins isolated from the octocoral Pseudopterogorgia elisabethae of San Andrés and Providencia Islands (Southwest Caribbean Sea). Mar Drugs 9:334–344 Bowers Z, Caraballo D, Bentley A (2021) Therapeutic potential of pseudopterosin H on a prostate cancer cell line. J Cancer Prev Curr Res 12:82–91 Ly C, Shimizu AJ, Vargas MV, Duim WC, Wender PA, Olson DE (2020) Bryostatin 1 promotes synaptogenesis and reduces dendritic spine density in cortical cultures through a PKC-dependent mechanism. ACS Chem Neurosci 11:1545–1554 Hong DS, Concin N, Vergote I, De Bono JS, Slomovitz BM, Drew Y, Arkenau HT, Machiels JP, Spicer JF, Jones R, Forster MD (2020) Tisotumab vedotin in previously treated recurrent or metastatic cervical cancer. Clin Can Res 26:1220–1228 Costantino V, Fattorusso E, Imperatore C, Mangoni A (2003) Ectyoceramide, the first natural hexofuranosylceramide from the marine sponge Ectyoplasia ferox. Eur J Org Chem 2003(8):1433–1437 Costantino V, Fattorusso E, Imperatore C, Mangoni A (2008) Glycolipids from sponges. 20. J-coupling analysis for stereochemical assignments in furanosides: structure elucidation of vesparioside B, a glycosphingolipid from the marine sponge Spheciospongia vesparia. J Org Chem 73:6158–6165 Malve H (2016) Exploring the ocean for new drug developments: marine pharmacology. J Pharm Bioallied Sci 8:83 Jaspars M, De Pascale D, Andersen JH, Reyes F, Crawford AD, Ianora A (2016) The marine biodiscovery pipeline and ocean medicines of tomorrow. J Mar Biol Ass U K 96:151–158 Löwenberg B (2013) Sense and nonsense of high-dose cytarabine for acute myeloid leukemia. J Am Soc Hematol 121:26–28 Menis J, Twelves C (2011) Eribulin (Halaven): a new, effective treatment for women with heavily pretreated metastatic breast cancer. Breast Cancer 3:101 Klotz U (2006) Ziconotide-a novel neuron-specific calcium channel blocker for the intrathecal treatment of severe chronic pain-a short review. Int J Clin Pharm Ther 44(10):478–483 Sagar S, Kaur M, Minneman KP (2010) Antiviral lead compounds from marine sponges. Mar Drugs 8:2619–2638 Umeyama A, Matsuoka N, Mine R, Nakata A, Arimoto E, Matsui M, Shoji N, Arihara S, Takei M, Hashimoto T (2010) Polyacetylene diols with antiproliferative and driving Th1 polarization effects from the marine sponge Callyspongia sp. J Nat Med 64(2010):93–97 Takei M, Umeyama A, Shoji N, Hashimoto T (2010) Polyacetylenediols regulate the function of human monocyte-derived dendritic cells. Int Immunopharmacol 10:913–921 Velmurugan BK, Lee CH, Chiang SL, Hua CH, Chen MC, Lin SH, Yeh KT, Ko YC (2018) PP2A deactivation is a common event in oral cancer and reactivation by FTY720 shows promising therapeutic potential. J Cell Phys 233:1300–1311 Lin Z, Antemano RR, Hughen RW, Tianero MDB, Peraud O, Haygood MG, Concepcion GP, Olivera BM, Light A, Schmidt EW (2010) Pulicatins A−E, neuroactive thiazoline metabolites from cone snail-associated bacteria. J Nat Prod 73:1922–1926 Asolkar RN, Freel KC, Jensen PR, Fenical W, Kondratyuk TP, Park EJ, Pezzuto JM (2009) Arenamides A− C, cytotoxic NFκB inhibitors from the marine actinomycete Salinispora arenicola. J Nat Prod 72:396–402 Ueoka R, Nakao Y, Kawatsu S, Yaegashi J, Matsumoto Y, Matsunaga S, Furihata K, Van Soest RW, Fusetani N (2009) Gracilioethers A−C, antimalarial metabolites from the marine sponge Agelas gracilis. J Org Chem 74:4203–4207 Martins A, Vieira H, Gaspar H, Santos S (2014) Marketed marine natural products in the pharmaceutical and cosmeceutical industries: tips for success. Mar Drugs 12(2):1066–1101 Molinski TF, Dalisay DS, Lievens SL, Saludes JP (2009) Drug development from marine natural products. Nat Rev Drug Dis 8(1):69–85 Montaser R, Luesch H (2011) Marine natural products: a new wave of drugs? Future Med Chem 3(12):1475–1489