Synthesis and biological evaluation of novel aryloxyacetic acid hydrazide derivatives as anticancer agents

In our continuing search for new anticancer agents, herein we report the synthesis of 2-(4-chloro-3-methylphenoxy)-N'-[(aryl)methylidene]acetohydrazides 3a-j and the evaluation of their anticancer activities on cell viability, morphological changes and caspase-3 activity in cancer cell lines including gastric cancer (MKN45), cervical cancer (HeLa) and breast cancer (MDA-MB-231) cells. 2-(4-chloro-3-methylphenoxy)-N'-[(4-phenylthiophen-2-yl)methylidene] acetohydrazide 3g presented the strongest growth inhibition against MKN45 gastric cancer cell lines with the IC50 value of 1.471 +/- 0.23 mu M. Moreover, compounds 3b and 3g showed high potency against the HeLa and MDA-MB-231 cell lines having IC50 in the range of 2.38-9.72 mu M. These compounds are more selective for the tested human cancer cells than for the mouse fibroblast cell line (NIH/3T3). As a result of the studies conducted in order to understand the molecular mechanism, compounds 3b and 3g enhanced expression of the caspase-3 pro-apoptotic proteins levels besides caspase-3 gene.

Automated summary

Novel anticancer compounds were synthesized in this study, with compound 3g showing the strongest growth inhibition against gastric cancer cell lines. Compounds 3b and 3g also demonstrated high potency against cervical and breast cancer cell lines. These compounds exhibit greater selectivity for human cancer cells and could be potential anticancer agents.