Synthesis, biological evaluation, and structure–activity relationship study of novel cytotoxic aza-caffeic acid derivatives

摘要: Abstract Three series of aza-caffeic acid derivatives with different linkers were designed and synthesized. Each the synthesized was then used in cytotoxicity screening on either 8 or 12 human cancer cell lines. The structure–activity relationships three structural regions A, B, C are analyzed detail, indicating that a nine bond linker containing piperazine unit, is most favorable leading to generation molecules potent cytotoxicities. Compound ( E )-1-(4-(3,4-dichlorobenzyl)piperazin-1-yl)-3-(4-(4-ethoxybenzyloxy)-3,5-dimethoxyphenyl)prop-2-en-1-one 80 ) exhibited significant selective KB, BEL7404, K562, Eca109 lines, IC 50 values 0.2, 2.0, 1.7, 1.1 μM, respectively, stronger than seen for caffeic phenethyl ester (CAPE) cisplatin (CDDP). Flow cytometric western blot analysis indicate compound plays role mitochondria-dependent apoptosis activity by suppressing K562 proliferation concentration- time-dependent manner.