International Journal of Pharmaceutical Science and Health Care Volume 15, Number 5, 2025 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 DOI: 10.5281/zenodo.17446284 Original Article ©2025 RS Publication, rspublicati[email protected] 168 Bioactive Compounds from Sponges and Corals: New Frontiers in Drug Discovery Mr. Ayan Biswas 1 1 Assistant Professor, Department of Zoology, Barasat Government College, 10, K.N.C. Road, Barasat, North 24-Paraganas, PIN700124, West Bengal, India. E-mail:
[email protected] ARTICLE INFO ABSTRACT ©2025 RS Publication Paper ID: IJPHC68FDA17B77414 Received: 2025-09-26 Published: 2025-10-26 DOI: https://dx.doi.org/ 10.5281/zenodo.1744 6284 Page No: 168-173 Marine ecosystems represent a vast and largely unexplored reservoir of pharmacologically active natural products. Among marine organisms, sponges and corals have emerged as prolific sources of structurally diverse and biologically potent compounds with significant therapeutic potential. These sessile invertebrates produce a wide array of secondary metabolites like alkaloids, terpenoids, peptides, polyketides, and sterols, that serve as chemical defenses against predation, microbial infection, and competition. Many of these metabolites exhibit potent anticancer, antimicrobial, antiviral, anti-inflammatory, and neuroprotective activities, often acting through novel molecular mechanisms. Recent advances in marine biotechnology, metagenomics, and synthetic biology have accelerated the discovery and sustainable production of these compounds, overcoming the limitations of natural harvesting. Notable examples include cytarabine, eribulin, and discodermolide, which have advanced from marine sponges to clinically approved drugs or promising leads. This review highlights the chemical diversity, pharmacological potential, and biotechnological innovations driving the translation of spongeand coral-derived compounds into modern therapeutics, emphasizing their importance in the post genomic era of drug discovery. Keywords: Marine natural products, Porifera, Anthozoa, Secondary metabolites, Drug discovery, Marine biotechnology Corresponding Author: Mr. Ayan Biswas International Journal of Pharmaceutical Science and Health Care Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 Cite This Paper: Mr. Ayan Biswas (2025). "Bioactive Compounds from Sponges and Corals: New Frontiers in Drug Discovery". INTERNATIONAL JOURNAL PHARMACEUTICAL SCIENCE AND HEALTH CARE (IJPHC), vol. 15, no. 5, 2025, pp. 168-173. DOI: https://dx.doi.org/10.5281/zenodo.17446284
International Journal of Pharmaceutical Science and Health Care Volume 15, Number 5, 2025 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 DOI: 10.5281/zenodo.17446284 Original Article ©2025 RS Publication, rspublicati[email protected] 169 1. Introduction The ocean covers over 70% of Earth’s surface and harbors an extraordinary diversity of life forms adapted to extreme ecological niches. Marine organisms have evolved unique biochemical pathways that produce structurally diverse secondary metabolites not found in terrestrial species. These bioactive compounds play key ecological roles and have become an invaluable source for pharmaceutical innovation. Marine sponges (belong to the phylumPorifera) and corals (phylumAnthozoa) represent two of the most chemically prolific groups of marine invertebrates. Their sessile lifestyles and exposure to intense competition and predation have driven the evolution of potent chemical defense mechanisms. As a result, sponges and corals synthesize metabolites with unusual molecular scaffolds and high biological activity, many of which interact with cellular targets that are relevant to human disease. Here a comprehensive synthesis of the chemical diversity, pharmacological potential, and recent technological advances enabling the sustainable exploration of spongeand coral-derived bioactive compounds for modern drug discovery has been organized. 2. Marine Sponges: Chemical and Biological Diversity 2.1 Overview of Sponge Metabolites Sponges are the oldest metazoans (sometimes classified as parazoa), possessing remarkable metabolic versatility due to their symbiotic associations with bacteria, fungi, and cyanobacteria. Approximately 30–60% of sponge biomass may consist of microbial symbionts, which contribute significantly to their chemical repertoire. The metabolites isolated from sponges encompass diverse chemical classes, including alkaloids (e.g., manzamine A, hymenialdisine), polyketides (e.g., discodermolide, latrunculin A), terpenoids (e.g., avarol, manoalide), peptides (e.g., theonellamides), sterols and macrolides [1]. These compounds often display potent bioactivities against tumor cells, bacteria, viruses, and inflammatory pathways. 2.2 Anticancer Agents from Sponges Sponges have yielded several clinically relevant anticancer compounds. Cytarabine (Ara-C), derived from Cryptotethya crypta, was the first marine natural product to become a clinically approved anticancer drug, used in leukemia treatment. Eribulin mesylate, a synthetic analog of halichondrin B from Halichondria okadai, inhibits microtubule dynamics and is approved for metastatic breast cancer [2]. Other promising leads include discodermolide, which stabilizes microtubules similar to taxol, and peloruside A, a potent tubulin-binding macrolide. These discoveries underscore the pharmacological richness of sponges as a foundation for antineoplastic drug development. 2.3 Antimicrobial and Antiviral Compounds Sponge-derived compounds demonstrate broad-spectrum antimicrobial and antiviral properties. For example, manzamine A, a β-carboline alkaloid, shows potent antimalarial and antibacterial activity, whereas avinosol and crambescidin 800 exhibit antiviral action against herpes and HIV [3]. Recent research has focused on compounds with activity against drug-resistant pathogens, making sponge metabolites promising candidates in the fight against antimicrobial resistance.
International Journal of Pharmaceutical Science and Health Care Volume 15, Number 5, 2025 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 DOI: 10.5281/zenodo.17446284 Original Article ©2025 RS Publication, rspublicati[email protected] 170 3. Bioactive Compounds from Corals 3.1 Soft Corals and Their Metabolites Soft corals (Order Alcyonacea) are rich in terpenoid compounds, particularly diterpenes, sesquiterpenes, and steroids. These molecules often serve as potent cytotoxins and antiinflammatory agents [4]. Examples include sarcophine, pseudopterosin, and briantheolide, which exhibit strong bioactivity at micromolar concentrations. 3.2 Pseudopterosins: Marine Anti-inflammatory Agents The pseudopterosins, isolated from the Caribbean gorgonian Pseudopterogorgia elisabethae, represent a class of diterpene glycosides with potent anti-inflammatory and analgesic properties. These compounds inhibit eicosanoid biosynthesis and stabilize lysosomal membranes. Extracts containing pseudopterosins have even been incorporated into commercial skin-care products due to their wound-healing activity [5]. 3.3 Coral Steroids and Neuroprotective Compounds Coral-derived steroids such as cembrene, sinulariolide, and sarcophytol A demonstrate notable anti-tumor, anti-inflammatory, and neuroprotective effects. Sinulariolide, for example, induces apoptosis in hepatocellular carcinoma cells via mitochondrial pathways, while cembrane diterpenes modulate neuroinflammation and oxidative stress. 4. Ecological and Evolutionary Context of Marine Chemical Defense Marine sponges and corals occupy competitive benthic environments where spatial competition and predation are intense. Their production of toxic or deterrent metabolites provides a survival advantage. Evolutionarily, these compounds function as allelochemicals, antifoulants, and antimicrobial agents. Symbiotic microorganisms also play a critical role, particularly in sponges, where microbial consortia contribute biosynthetic gene clusters responsible for metabolite production. This symbiosis-driven metabolic diversity is now being harnessed through metagenomic and microbiome-based approaches for drug discovery. 5. Modern Biotechnological Approaches 5.1 Metagenomics and Genome Mining Traditional extraction from wild specimens is unsustainable and ecologically harmful. Metagenomic techniques allow scientists to sequence and analyze biosynthetic gene clusters from uncultured symbionts. Genome mining helps identify novel nonribosomal peptide synthetases (NRPS) and polyketide synthases (PKS) responsible for bioactive compound synthesis.
International Journal of Pharmaceutical Science and Health Care Volume 15, Number 5, 2025 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 DOI: 10.5281/zenodo.17446284 Original Article ©2025 RS Publication, rspublicati[email protected] 171 5.2 Synthetic Biology and Heterologous Expression Synthetic biology has enabled the transfer of marine biosynthetic genes into easily cultivable hosts such as E. coli or Streptomyces. This approach facilitates scalable production of compounds like palau’amide and onchidin, bypassing the need for large-scale marine collection [6]. 5.3 Sustainable Aquaculture and Cell Culture Techniques Coral and sponge cell culture systems are being developed to enable metabolite production in vitro. Marine bioreactors using sponge cell lines or coral fragments cultured under controlled conditions can yield stable metabolite outputs, representing a promising avenue for sustainable drug sourcing. 6. Pharmacological Potential and Mechanisms of Action 6.1 Anticancer as microtubule stabilization (eribulin, discodermolide) Marine sponges have yielded an exceptional array of cytotoxic metabolites with potent anticancer properties, primarily acting through interference with critical cellular processes such as microtubule dynamics, apoptosis induction, and DNA synthesis inhibition. Compounds like eribulin mesylate, a synthetic analog of halichondrin B from the sponge Halichondria okadai, and discodermolide from Discodermia dissoluta, exert their effects by stabilizing microtubules, thereby preventing their depolymerization during mitosis [2]. This stabilization disrupts spindle assembly, causes cell-cycle arrest at the G2/M phase, and ultimately triggers mitochondriamediated apoptosis through activation of caspase-3 and caspase-9 pathways. In parallel, several sponge-derived alkaloids and polyketides promote programmed cell death by enhancing p53 expression, altering the Bcl-2/Bax ratio, and promoting cytochrome c release from mitochondria. Other compounds, such as nucleoside analogs and sesquiterpenes, act as DNA polymerase or topoisomerase inhibitors, interfering with DNA replication and repair mechanisms, leading to replication stress and double-strand DNA breaks [7]. These multifaceted mechanisms contribute to the suppression of tumor proliferation and metastasis. 6.2 Antimicrobial as membrane disruption, quorum sensing inhibition, and inhibition of bacterial efflux pumps Many marine peptides and alkaloids, such as theonellamides from Theonella swinhoei, target bacterial membrane sterols and phospholipids, leading to membrane permeabilization, ion imbalance, and cell lysis [6]. In addition to direct bactericidal action, certain coral-derived furanones act as quorum sensing inhibitors (QSIs), blocking the acyl-homoserine lactone (AHL) signaling pathways that regulate biofilm formation and virulence gene expression in pathogens like Pseudomonas aeruginosa. Furthermore, several sponge metabolites, including bromotyrosine derivatives and pyrroloiminoquinones, inhibit bacterial efflux pumps (e.g., NorA, MexAB-OprM), thereby enhancing intracellular antibiotic accumulation and reversing multidrug resistance (MDR) [8].
International Journal of Pharmaceutical Science and Health Care Volume 15, Number 5, 2025 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 DOI: 10.5281/zenodo.17446284 Original Article ©2025 RS Publication, rspublicati[email protected] 172 6.3 Anti-inflammatory as cyclooxygenase and nitric oxide synthase inhibition (pseudopterosins) Pseudopterosins, a class of diterpene glycosides isolated from the coral Pseudopterogorgia elisabethae, exert their effects by inhibiting cyclooxygenase (COX-2) and inducible nitric oxide synthase (iNOS) enzymes, thereby reducing the synthesis of pro-inflammatory mediators such as prostaglandin E₂ (PGE₂) and nitric oxide (NO). These compounds further downregulate NF-κB and MAPK (ERK and p38) signaling pathways, leading to suppressed transcription of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) [9]. Through simultaneous inhibition of eicosanoid and reactive nitrogen species production, pseudopterosins effectively mitigate inflammatory responses, demonstrating their potential as novel marinederived anti-inflammatory therapeutics. 6.4 Neuroprotective as modulation of calcium channels and oxidative pathways (sinulariolide, cembrane diterpenes) Marine natural products such as sinulariolide and cembrane diterpenes, predominantly isolated from soft corals of the genus Sinularia, exhibit remarkable neuroprotective effects through the modulation of calcium signaling and oxidative stress pathways. These compounds regulate voltage-gated calcium channels (VGCCs) and NMDA receptor activity, preventing calcium overload -induced excitotoxicity, a key pathological event in neurodegenerative disorders. Additionally, they activate the Nrf2/ARE signaling cascade, leading to upregulation of endogenous antioxidant enzymes including superoxide dismutase (SOD), catalase, and heme oxygenase-1 (HO-1). This enhances neuronal resistance to reactive oxygen species (ROS) and mitigates mitochondrial dysfunction [10]. By simultaneously stabilizing intracellular calcium homeostasis and strengthening antioxidant defenses, sinulariolide and cembrane diterpenes provide a dual protective mechanism against neuronal apoptosis and oxidative damage, highlighting their potential in the development of therapeutics for neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Such multi-target pharmacological profiles make marine metabolites valuable candidates for multi-drug resistant diseases and chronic inflammatory disorders. 7. Conclusion Sponges and corals represent a frontier in natural product based pharmaceutical discovery. Their unparalleled chemical diversity, combined with technological advances in genomics and biotechnology, has reinvigorated marine pharmacology as a vital source of next generation therapeutics. The continued exploration of their metabolites holds immense promise for addressing pressing global health challenges, from cancer and infectious diseases to inflammation and neurodegeneration. Sustainable harvesting, ethical bioprospecting, and international cooperation
International Journal of Pharmaceutical Science and Health Care Volume 15, Number 5, 2025 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 DOI: 10.5281/zenodo.17446284 Original Article ©2025 RS Publication, rspublicati[email protected] 173 are essential to ensure that the pharmacological treasures of the sea are preserved and translated responsibly into medical innovation. References [1] Ancheeva, E., El-Neketi, M., Song, W., Lin, W., Daletos, G., Ebrahim, W. & Proksch, P. Structurally Unprecedented Metabolites from Marine Sponges. Curr. Org. Chem. 21(5), 2017. [2] Schwartsmann G, Brondani da Rocha A, Berlinck RG, Jimeno J. Marine organisms as a source of new anticancer agents. Lancet Oncol. 2001 Apr;2(4):221-225. [3] Ashok P, Ganguly S, Murugesan S. Manzamine alkaloids: isolation, cytotoxicity, antimalarial activity and SAR studies. Drug Discov Today. 2014 Nov;19(11):1781-1791. [4] Ng, S.-Y., Phan, C.-S., Ishii, T., Kamada, T. & Vairappan, C. S. “Terpenoids from Marine Soft Coral of the Genus Xenia in 1977 to 2019.” Molecules 25(22): 5386 (2020). [5] Look, S. A., Fenical, W., Jacobs, R. S. & Clardy, J. “The pseudopterosins: anti-inflammatory and analgesic natural products from the sea whip Pseudopterogorgia elisabethae.” Proc. Natl. Acad. Sci. USA 83 (17): 6238-6240 (1986). [6] Zhao S, Feng R, Gu Y, Han L, Cong X, Liu Y, Liu S, Shen Q, Huo L, Yan F. Heterologous expression facilitates the discovery and characterization of marine microbial natural products. Eng Microbiol. 2023 Dec 19;4(2):100137. [7] Jimeno A. Eribulin: rediscovering tubulin as an anticancer target. Clin Cancer Res. 2009 Jun 15;15(12):3903-5. [8] Boakye A, Seidu MP, Adomako A, Laryea MK, Borquaye LS. Marine-Derived Furanones Targeting Quorum-Sensing Receptors in Pseudomonas aeruginosa: Molecular Insights and Potential Mechanisms of Inhibition. Bioinform Biol Insights. 2024 Sep 5;18:11779322241275843. [9] Correa H., Valenzuela A. L., Ospina L. F., Duque C. “Anti-inflammatory effects of the gorgonian Pseudopterogorgia elisabethae collected at the Islands of Providencia and San Andrés (SW Caribbean).” J. Inflamm. 6: 5 (2009). [10] Rivai, B., Umar, A.K. Neuroprotective compounds from marine invertebrates. Beni-Suef Univ J Basic Appl Sci 12, 71 (2023).