| Summary: | One of the most widespread biotas in the sea is the sponge. <i>Callyspongia</i> is a sponge genus found in the seas, making it easily available. In this review, the pharmacological activity and mechanism of action of the secondary metabolites of <i>Callyspongia</i> spp. are addressed, which may lead to the development of new drugs and targeted therapeutic approaches. Several scientific databases, such as Google Scholar, PubMed, ResearchGate, Science Direct, Springer Link, and Wiley Online Library, were mined to obtain relevant information. In the 41 articles reviewed, <i>Callyspongia</i> spp. was reported to possess pharmacological activities such as cytotoxicity against cancer cell lines (36%), antifungal (10%), anti-inflammatory (10%), immunomodulatory (10%), antidiabetic and antiobesity (6%), antimicrobial (8%), antioxidant (4%), antineurodegenerative (4%), antihypercholesterolemic (2%), antihypertensive (2%), antiparasitic (2%), antiallergic (2%), antiviral (2%), antiosteoporotic (2%), and antituberculosis (2%) activities. Of these, the antioxidant, antituberculosis, and anti-inflammatory activities of <i>Callyspongia</i> extract were weaker compared with that of the control drugs; however, other activities, particularly cytotoxicity, show promise, and the compounds responsible may be developed into new drugs.
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