Chapter 6. Stevensine: A Bromopyrrole Alkaloid from Marine Sponges


Ankit Kumar1,2, Rekha Jethi3, Ravindra Semwal1, Ganesh Kumarand Deepak Kumar Semwal4
Research and Development Centre, Faculty of Biomedical Sciences, Uttarakhand Ayurved University, Dehradun, India
2College of Pharmacy, Shivalik campus, Dehradun, India
3Patanjali Research Institute, Patanjali Yogpeeth, Haridwar, Uttarakhand, India
4Department of Phytochemistry, Faculty of Biomedical Science, Uttarakhand Ayurved University, Dehradun, India

Part of the book: The Essential Guide to Alkaloids


The dependency of humankind on nature for food and medicine, since time immemorial, has continued so far. Plants, animals, micro-organisms and marine organisms are excellent sources of bioactive molecules like alkaloids, glycosides, steroids, tannins, flavonoids, terpenoids and saponins etc. Due to the efficacy and potency of the naturally derived molecules, at present, no alternative is available for natural molecules, such as morphine, digitoxin, quinine, penicillin and cephalosporin. Due to the development of resistance against current medication in the case of micro-organism infection, parasite infection and cancer, the need for a new compensatory generation of therapeutic agents is today’s demand. Other than plants, animals and microorganisms, marine life has been introduced as an alternative source of medicinal agents in the last 50 years. At present, more than 200,000 marine species, as representative of each Phylum, are found in the ocean. About 30,000 bioactive compounds have been discovered in marine organisms. More than 8,500 species of sponges, are scientifically documented and identified but Researchers believed more than 25,000 species exist in the ocean. As a source of medicine, about 5,300 bioactive compounds are reported in marine sponges from diverse chemical classes, like alkaloids, peptides, and terpenoids. This book chapter discussed biological source, synthesis and pharmacological studies of a bromopyrrole alkaloid “Stevensine” isolated from different species of marine sponge. It was also synthesized from the related marine alkaloid hymenin. Stevensine has been shown several pharmacological potentials in different in-vitro and in-vivo studies, such as protein kinase inhibitor, neurological, anti-microbial, anti-tubercular, anti-cancer and anti-parasite activity. The previously available report concludes that further studies are needed to explore the mechanism of action of stevensine in cancer, diabetes and neurological disorders.

Keywords: alkaloids, marine compounds, sponges, protein kinase inhibitory


Acquah, K. S., Beukes, D. R., Seldon, R., Jordaan, A., Sunassee, S. N., Warner, D. F., &
Gammon, D. W. (2022). Identification of antimycobacterial natural products from a
library of marine invertebrate extracts. Medicines, 9(2), 9.
Aiello, A., D’Esposito, M., Fattorusso, E., Menna, M., Müller, W. E. G., Perović-Ottstadt,
S., & Schröder, H. C. (2006). Novel bioactive bromopyrrole alkaloids from the
Mediterranean sponge Axinella verrucosa. Bioorganic & Medicinal Chemistry, 14(1),
Albizati, K. F., & Faulkner, D. J. (1985). Stevensine, a novel alkaloid of an unidentified
marine sponge. Journal of Organic Chemistry, 50(21), 4163–4164.
Andrade, P., Willoughby, R., Pomponi, S. A., & Kerr, R. G. (1999). Biosynthetic studies
of the alkaloid, stevensine, in a cell culture of the marine sponge Teichaxinella
morchella. Tetrahedron Letters, 40(26), 4775–4778.
Andrews, K. T., Fisher, G., & Skinner-Adams, T. S. (2014). Drug repurposing and human
parasitic protozoan diseases. International Journal for Parasitology: Drugs and Drug
Resistance, 4(2), 95-111.
Anshabo, A. T., Milne, R., Wang, S., & Albrecht, H. (2021). CDK9: a comprehensive
review of its biology, and its role as a potential target for anti-cancer agents. Frontiers
in Oncology, 11, 678559.
Arrow, K. J., Panosian, C., & Gelband, H. (2004). Antimalarial drugs and drug resistance.
In : Saving Lives, Buying Time: Economics of Malaria Drugs in an Age of Resistance.
National Academies Press (US).
Bar-On, Y. M., Phillips, R., & Milo, R. (2018). The biomass distribution on Earth.
Proceedings of the National Academy of Sciences, 115(25), 6506-6511
Bickmeyer, U., Grube, A., Klings, K.-W., & Köck, M. (2007). Disturbance of voltage-induced cellular
calcium entry by marine dimeric and tetrameric pyrrole–imidazole
alkaloids. Toxicon, 50(4), 490–497.
Buynak, J. D. (2004). The discovery and development of modified penicillin-and
cephalosporin-derived β-lactamase inhibitors. Current Medicinal Chemistry, 11(14),
Cheng, S., Yang, G. J., Wang, W., Ma, D. L., & Leung, C. H. (2022). Discovery of a
tetrahydroisoquinoline-based CDK9-cyclin T1 protein–protein interaction inhibitor as
an anti-proliferative and anti-migration agent against triple-negative breast cancer
cells. Genes & Diseases, 9(6), 1674-1688.
Cheung, R. C. F., Ng, T. B., Wong, J. H., Chen, Y., & Chan, W. Y. (2015). Marine natural
products with anti-inflammatory activity. Applied Microbiology and Biotechnology,
100(4), 1645–1666.
de Oliveira, M. F., de Oliveira, J. H., Galetti, F. C., de Souza, A. O., Silva, C. L., Hajdu,
E., Peixinho, S., & Berlinck, R. G. (2006). Antimycobacterial brominated metabolites
from two species of marine sponges. Planta Medica, 72(05), 437-441.
Ebada, S. S., & Proksch, P. (2012). The chemistry of marine sponges∗. Handbook of marine
natural products, 191-293.
Ebada, S. S., Linh, M. H., Longeon, A., de Voogd, N. J., Durieu, E., Meijer, L., Bourguet-Kondracki, M. L., Singab, A. N., Müller, W. E., & Proksch, P. (2014). Dispacamide
E and other bioactive bromopyrrole alkaloids from two Indonesian marine sponges of
the genus Stylissa. Natural Product Research, 29(3), 231–238.
Eldar-Finkelman, H., & Martinez, A. (2011). GSK-3 inhibitors: preclinical and clinical
focus on CNS. Frontiers in molecular neuroscience, 4, 32.
Farmer, G. T., & Cook, J. (2013). The World Ocean. In : Climate Change Science: A
Modern Synthesis (pp. 247-259). Springer, Dordrecht.
Fattorusso, E., & Taglialatela-Scafati, O. (2009). Marine antimalarials. Marine Drugs, 7(2),
Faulkner D. J. 1991 Marine natural products. Nat Prod Rep 8:97-147, and earlier reports
Scheuer P. J. (ed.) 1991 Bioorganic marine chemistry, vol IV. Springer-Verlag, Berlin,
and earlier volumes.
Fenical, W. (1999). Marine-derived pharmaceuticals and related bioactive agents. From
Monsoons to Microbes, Understanding the Ocean’s Role in Human Health, 73-82.
Fiore, C., Baraghini, A., Shemchuk, O., Sambri, V., Morotti, M., Grepioni, F., & Braga, D.
(2022). Inhibition of the Antibiotic Activity of Cephalosporines by Co-Crystallization
with Thymol. Crystal Growth & Design, 22(2), 1467-1475.
Fouad, M. A., Debbab, A., Wray, V., Müller, W. E. G., & Proksch, P. (2012). New
bioactive alkaloids from the marine sponge Stylissa sp. Tetrahedron, 68(49), 10176–10179.
Hafez Ghoran, S., & Kijjoa, A. (2021). Marine-Derived Compounds with Anti-Alzheimer’s
Disease Activities. Marine Drugs, 19(8), 410.
Janovská, P., Normant, E., Miskin, H., & Bryja, V. (2020). Targeting casein kinase 1 (CK1)
in hematological cancers. International Journal of Molecular Sciences, 21(23), 9026.
Kim, S. K., & Karadeniz, F. (2011). Anti-HIV activity of extracts and compounds from
marine algae. Advances in food and nutrition research, 64, 255-265.
Kiuru P, D’Auria MV, Muller CD, Tammela P, Vuorela H, Yli-Kauhaluoma J. Exploring
marine resources for bioactive compounds. Planta Med. 2014;80:1234–1246. Marine
Kobayashi, J., Ohizumi, Y., Nakamura, H., Hirata, Y., Wakamatsu, K. and Miyazawa, T.
(1986). Hymenin, a novel a-adrenoceptor blocking agent from the Okinawan marine
sponge Hymeniacidon sp. Experientia, 42(9), 1064-1065.
Mapelli, M., & Musacchio, A. (2003). The structural perspective on CDK5. Neurosignals,
12(4-5), 164-172.
Martín Moyano, P., Němec, V., & Paruch, K. (2020). Cdc-like kinases (CLKs): biology,
chemical probes, and therapeutic potential. International Journal of Molecular
Sciences, 21(20), 7549.
Masch, A., & Kunick, C. (2015). Selective inhibitors of Plasmodium falciparum glycogen
synthase-3 (PfGSK-3): new antimalarial agents?. Biochimica et Biophysica Acta
(BBA)-Proteins and Proteomics, 1854(10), 1644-1649.
Mayer, A. M., & Gustafson, K. R. (2004). Marine pharmacology in 2001–2: antitumour
and cytotoxic compounds. European Journal of Cancer, 40(18), 2676-2704.
Mohammed, R., Peng, J., Kelly, M., & Hamann, M. T. (2006). Cyclic Heptapeptides from
the Jamaican Sponge Stylissa caribica. Journal of Natural Products, 69(12), 1739–1744.
Newbold, R. W., Jensen, P. R., Fenical, W., & Pawlik, J. R. (1999). Antimicrobial activity
of Caribbean sponge extracts. Aquatic microbial ecology, 19(3), 279-284.
Nguyen, T., & Tepe, J. (2009). Preparation of Hymenialdisine, Analogues and Their
Evaluation as Kinase Inhibitors. Current Medicinal Chemistry, 16(24), 3122–3143.
Rao, K. V., Donia, M. S., Peng, J., Garcia-Palomero, E., Alonso, D., Martinez, A., … &
Hamann, M. T. (2006). Manzamine B and E and ircinal A related alkaloids from an
Indonesian Acanthostrongylophora sponge and their activity against infectious,
tropical parasitic, and Alzheimer’s diseases. Journal of natural products, 69(7), 1034-1040.
Renard, E., Gazave, E., Fierro-Constain, L., Schenkelaars, Q., Ereskovsky, A., Vacelet, J.,
& Borchiellini, C. (2013). Porifera (sponges): recent knowledge and new perspectives.
Rinehart, K. L. (2007). Secondary Metabolites from Marine Organisms. Novartis
Foundation Symposia, 236–254.
Rodríguez, I. I., Rodríguez, A. D., Wang, Y., & Franzblau, S. G. (2006). Ileabethoxazole:
a novel benzoxazole alkaloid with antimycobacterial activity. Tetrahedron Letters,
47(19), 3229-3232.
Scala, F., Fattorusso, E., Menna, M., Taglialatela-Scafati, O., Tierney, M., Kaiser, M., &
Tasdemir, D. (2010). Bromopyrrole Alkaloids as Lead Compounds against Protozoan
Parasites. Marine Drugs, 8(7), 2162–2174.
Semwal, D. K., Kumar, A., Semwal, R. B., & Andola, H. C. (2021). Convolvulus
prostratus. In : Naturally Occurring Chemicals Against Alzheimer’s Disease (pp. 409-
424). Academic Press.
Shah B. N. and Seth A. K. (2014). Textbook of pharmacognosy and phytochemistry.
Elsevier India. 2nd Edition.
Sunada, S., Saito, H., Zhang, D., Xu, Z., & Miki, Y. (2021). CDK1 inhibitor controls G2/M
phase transition and reverses DNA damage sensitivity. Biochemical and Biophysical
Research Communications, 550, 56-61.
Tadesse, S., Caldon, E., Tilley, W., & Wang, S. (2018). Cyclin Dependent Kinase 2
Inhibitors in Cancer Therapy: an Update. Journal of Medicinal Chemistry.
Umumararungu, T., Mukazayire, M. J., Mpenda, M., Mukanyangezi, M. F., Nkuranga, J.
B., Mukiza, J., & Olawode, E. O. (2020). A review of recent advances in anti-tubercular drug development. Indian journal of tuberculosis, 67(4), 539-559.
Vitale, R. M., Rispoli, V., Desiderio, D., Sgammato, R., Thellung, S., Canale, C., Vassalli,
M., Carbone, M., Ciavatta, M. L., Mollo, E., Felicità, V., Arcone, R., Gavagnin
Capoggiani, M., Masullo, M., Florio, T., & Amodeo, P. (2018). In Silico identification
and experimental validation of novel anti-alzheimer’s multitargeted ligands from a
marine source featuring a “2-aminoimidazole plus aromatic group” scaffold. ACS
Chemical Neuroscience, 9(6), 1290-1303.
Wang, C., Lu, Y., & Cao, S. (2020). Antimicrobial compounds from marine actinomycetes.
Archives of pharmacal research, 43(7), 677-704.
World Health Organization. (2022). Retrieved on 03 September from
Xu, Y., Yakushijin, K., & Horne, D. A. (1996). Transbromination of brominated pyrrole
and imidazole derivatives: Synthesis of the C11N5 marine alkaloid stevensine.
Tetrahedron Letters, 37(45), 8121–8124.
Xu, Y., Yakushijin, K., & Horne, D. A. (1997). Synthesis of C11N5Marine Sponge
Alkaloids: (±)-Hymenin, Stevensine, Hymenialdisine, and Debromohymenialdisine.
The Journal of Organic Chemistry, 62(3), 456–464.
Yoon, H. R., Balupuri, A., Choi, K. E., & Kang, N. S. (2020). Small molecule inhibitors of
DYRK1A identified by computational and experimental Approaches. International
journal of molecular sciences, 21(18), 6826.
Zhang, H., Khalil, Z., Conte, M. M., Plisson, F., & Capon, R. J. (2012). A search for kinase
inhibitors and antibacterial agents: bromopyrrolo-2-aminoimidazoles from a deep-water Great Australian Bight sponge, Axinella sp. Tetrahedron Letters, 53(29), 3784–3787.
Zhang, M., Zhang, L., Hei, R., Li, X., Cai, H., Wu, X., … & Cai, C. (2021). CDK inhibitors
in cancer therapy, an overview of recent development. American journal of cancer
research, 11(5), 1913


Publish with Nova Science Publishers

We publish over 800 titles annually by leading researchers from around the world. Submit a Book Proposal Now!