Anticancer potential of piericidin A1 and derivatives isolated from Streptomyces sp. associated with Palythoa variabilis from Brazilian Reefs

Marine holobionts are prolific sources of bioactive natural products. Previously, our group investigated cytotoxic compounds in zoantharians of the genus Palythoa and, herein, we further explored the anticancer potential of marine bacteria associated with P. variabilis . After isolating 10 culturable bacterial strains, we screened for cytotoxic activity on metastatic prostate tumor cells (PC-3/M) using the MTT assay. The crude extract of one of the strains (BRA-035), identified as Streptomyces sp., was selected due to its bioactivity profile and submitted to cytotoxicity-guided fractionation. This approach allowed us to isolate piericidin A1 and identify other 2 piericidin derivatives. Piericidin A1 displayed a wide range of potency, with IC ₅₀ varying from pM to low nM for several tumor cells (OVCAR, PC-3, PC-3/M, HCT-116) or non active (IC ₅₀ >12uM) for leukemia cell line (HL-60) and murine melanoma (B16-F10). Overall, our findings demonstrate that P. variabilis hosts bacteria with biotechnological potential, confirming piericidin A1 as a promising candidate for anticancer applications.