Small Structural Changes in Chili-Derived Capsaicin Resulting in Nonivamide Analogs of Significantly Improved Cytotoxicity and Good Tumor/Non-Tumor Cell Selectivity.

ABSTRACT: Capsaicin, the major pungent alkaloid in Capsicum species, has been reported to exhibit cytotoxic activity through various mechanisms. In this study, capsaicin and 37 structurally related vanillylamide and ester analogs were synthesized and evaluated for cytotoxic activity and tumor cell/non-tumor cell selectivity in vitro and compared with a Capsicum baccatum (Aji mochero) extract. Seven analogs with superior potency and selectivity compared to capsaicin were identified. Notably, vanillylamides with a C₁₆-C₁₈ chain exhibited IC₅₀ values five-fold lower than capsaicin (15-84 µM), with selectivity indices up to 35. The extract obtained from the dried chili fruit, known to hold capsaicin as its primary component, however, exhibited signif

SUBMITTER: Heise NV 

PROVIDER: S-EPMC12429925 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature