Synthesis and Biological Evaluation of New Madecassic Acid Derivatives Targeting ERK Cascade Signaling.

ABSTRACT: In the present study, a series of novel madecassic acid derivatives was synthesized and screened against the National Cancer Institute's 60 human cancer cell line panel. Among them, compounds 5, 12, and 17 displayed potent and highly differential antiproliferative activity against 80% of the tumor cells harboring the B-Raf^V600E mutation within the nanomolar range. Structure-activity analysis revealed that a 5-membered A ring containing an α,β-unsaturated aldehyde substituted at C-23 with a 2-furoyl group seems to be crucial to produce this particular growth inhibition signature. In silico analysis of the cytotoxicity pattern of these compounds identified two highly correlated clinically approved drugs with known B-Raf^V600E inhibitory activi

SUBMITTER: Valdeira ASC 

PROVIDER: S-EPMC6172662 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature