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

Abstract

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 μM. 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 μM. 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.

Graphical Abstract

Keywords:

• Anticancer activity
• caspase-3
• cresol
• cytotoxicity
• hydrazone
• synthesis

Disclosure statement

The authors have declared no conflict of interest.