Bioactive metabolites of Brazilian Red Propolis: Cytotoxic, antimalarial, and antimicrobial properties

Brazilian Red Propolis (BRP) is a natural product known for its rich chemical composition and therapeutic potential. This study investigates the phytochemical profile and evaluates the cytotoxic, antiplasmodial, and antimicrobial properties of red propolis extract and its isolated compounds vestitol (1), neovestitol (2), medicarpin (3), 7-O-methylvestitol (4), and oblongifolin B (5). The extract showed selective cytotoxicity against cancer cell lines (IC₅₀: 16-39 μg/mL). Compound 3 exhibited a promising cytotoxicity against SK-OV-3 with and IC₅₀ of 6.65 μM. BRP had moderate antimicrobial effects; however, 3 was effective against Cryptococcus neoformans (IC₅₀: 19.29 μM), while 5 was active against Pseudomonas aeruginosa (IC₅₀: 15.77 μM). BRP exhibited antiplasmodial activity against Plasmodium falciparum strains D6 and W2 (IC₅₀: 13.8 μg/mL and 5.7 μg/mL); also, 4 and 5 had IC₅₀ concentrations ranging from: 2.99-6.96 μM). Molecular docking for P. falciparum lactate dehydrogenase (PfLDH), suggest that compound 4 has significant interactions with critical residues in the PfLDH active site, such as TYR85, THR97, and ASP53, and falls within optimal ranges for oral bioavailability. These findings highlight the significant bioactive potential of BRP and its compounds, suggesting their potential as therapeutic agents in vitro and in-silico. Further studies are recommended to explore their mechanisms of action and therapeutic applications.