Synthetic esterification of yacon sesquiterpene lactone, sonchifolinic acid led to cytotoxic SARs study

Abstract

Cytotoxicity on sonchifolinic acid (1) isolated from Samallunthus leaf and synthetic compounds related to compound 1 were comparatively studied for the first time. Derivatives of 1 such as propyl (1a), butyl (1b), pentyl (1c) and 2-methoxy ethyl (1d) sonchifolate were prepared and their cytotoxic activity on HeLa cells were compared with sonchifolin (2), a structurally related natural compound. Alkylation of the carboxylic acid group at C-14 position in 1 enhanced the cytotoxic activity 2-5 times (1a - 1d and 2, IC50 5.29 - 21.07 μM) compared with that of sonchifolinic acid (1) (IC50 47.12 μM). Higher lipophilicity and moderate bulkiness of the inserted alkyl group contributed to the increased SL cytotoxicity in vitro. This result shows sonchifolinic acid (1) could be a valuable leading compound for semi-synthetic derivatives in order to develop new potent anticancer drugs.