Unlocking Marine Microbial Metabolites of Sponges and Sediments as a Source of Anti‐ <i>Trypanosoma cruzi</i> Compounds

Marine microbial metabolites have long served as valuable sources for drug discovery, exhibiting diverse biological activities, including antiparasitic, antimicrobial, and antiviral effects. Chagas disease (CD), a neglected tropical disease caused by Trypanosoma cruzi, affects approximately 8 million people worldwide. Currently, only two drugs are available for treatment, both associated with significant toxicity, underscoring the urgent need for new therapeutic alternatives. In this context, and considering the remarkable chemical diversity of marine bacteria, the present study investigated the anti-T. cruzi potential of metabolites produced by sediment- and sponge-associated microbial communities from Buzios Island, Brazil. The sponges were identified as Cinachyrella alloclada and Haliclona (Soestella) caerulea. Using 16S rRNA gene sequencing, nine marine bacterial isolates were identified, belonging to the genera Dokdonia, Vibrio, Alteromonas, Planococcus, Shewanella, Micrococcus, and Pseudoalteromonas. The antiparasitic activity of the extracts was evaluated against trypomastigote forms, yielding potent IC₅₀ values ranging from 1 to 87 µg/mL. Dereplication studies based on ¹H nuclear magnetic resonance and high-performance liquid chromatography-tandem mass spectrometry analyses of the Pseudoalteromonas piscicida extract revealed putative antitrypanosomal compounds, annotated as alkaloids and polycyclic tetramate macrolactams. Overall, this study demonstrates the high pharmacological potential of marine bacterial strains as sources of drug candidates for CD.