Novel N‐pyrocatechoyl and N‐pyrogalloyl hydrazone antioxidants endowed with cytotoxic and antibacterial activity

Abstract

Over the years, pharmacological agents bearing antioxidant merits arose as beneficial in the prophylaxis and treatment of various health conditions. Hazardous effects of radical species hyperproduction disrupt normal cell functioning, thus increasing the possibility for the development of various oxidative stress‐associated disorders, such as cancer. Contributing to the efforts for efficient antioxidant drug discovery, a thorough in vitro and in silico assessment of antioxidant properties of 14 newly synthesized N‐pyrocatechoyl and N‐pyrogalloyl hydrazones (N‐PYRs) was accomplished. All compounds exhibited excellent antioxidant potency against the 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) radical. The extensive in silico analysis revealed multiple favorable features of N‐PYRs to inactivate harmful radical species, which supported the obtained in vitro results. Also, in silico experiments provided insights into the preferable antioxidant pathways. Prompted by these findings, the cytotoxicity effects and the influence on the redox status of cancer HCT‐116 cells and healthy fibroblasts MRC‐5 were evaluated. These investigations exposed four analogs exhibiting both cytotoxicity and selectivity toward cancer cells. Furthermore, the frequently uncovered antimicrobial potency of hydrazone‐type hybrids encouraged investigations on G+ and G– bacterial strains, which revealed the antibacterial potency of several N‐PYRs. These findings highlighted the N‐PYRs as excellent antioxidant agents endowed with cytotoxic and antibacterial features.