CHEMICAL DIVERSITY AND PHARMACOLOGICAL ACTIVITIES OF FRESHWATER SPONGE-DERIVED METABOLITES: A SYSTEMATIC REVIEW

Freshwater sponges (Porifera) are underexplored sources of structurally diverse natural products with emerging pharmacological potential. This systematic review synthesized evidence on the chemical diversity and biological activities of freshwater sponge-derived metabolites and evaluated their predicted drug-likeness and pharmacokinetic properties. The review followed PRISMA 2020 guidelines and was prospectively registered in PROSPERO (CRD420250626419). Scopus, Web of Science, PubMed/MEDLINE, and Embase were systematically searched from database inception to 20 January 2025 for experimental studies investigating freshwater sponge extracts or isolated metabolites. Nine studies met the inclusion criteria. Antioxidant activity was the most consistently reported activity, with evidence of free-radical scavenging, oxidative-stress modulation, and changes in redox-associated biomarkers. Antimicrobial, cytotoxic, and genotoxic were also reported, whereas no included study provided direct experimental evidence of anti-inflammatory activity. Chemical characterization identified diverse metabolite classes, including fatty acids, sterols, peptides, glycolipids, alkaloids, and terpenoids. SwissADME and Deep-PK analyses indicated that several metabolites possess favourable physicochemical and predicted pharmacokinetic properties, although some structurally complex compounds exceeded conventional Lipinski criteria. Overall, the evidence indicates that freshwater sponge-derived metabolites represent an underexplored chemical resource with diverse biological activities and potential relevance to natural-product drug discovery. The integration of chemical characterization, experimental bioactivity, and computational assessment identifies priority areas for metabolite isolation, mechanistic validation, and pharmacological development.