Design, Synthesis, Biological Evaluation, and Molecular Docking Studies of 4‐Nitrobenzohydrazide Derivatives as Potential Anticancer Agents

Abstract A series of new acylhydrazone derivatives were synthesized from the condensation of different substituted salicylaldehydes with 4‐nitrobenzohydrazide at a molar ratio of 1 : 1 in a one‐step reaction. These compounds have been characterized by spectroscopic techniques such as FT‐IR, NMR, ESI‐MS and CHN analysis. All compounds were examined for anticancer activity in three cancer cell lines viz. melanoma (A375), colon (HT‐29) and lung (A549). Compound 3 exhibits good cytotoxicity activity with an IC 50 value of 0.38±0.08 μM against A375 and compound 2 exhibits better cytotoxicity 1.34±0.02 μM and 1.48±0.04 μM against HT‐29 and A549, respectively. Similarly, other compounds have also shown significant cytotoxicity activity against three cell lines. The cytocompatibility assay on the normal mouse fibroblast cell line (L929) and the hemolysis assay on human red blood cells were used to confirm the nontoxic activity. DAPI(4 ′ ,6‐diamidino‐2‐phenyliindole) staining experiments demonstrated that compounds induced apoptosis in the A375 cell line. Further, in silico molecular docking was performed against three various targets. In silico studies demonstrated that compounds 1 (ΔGb=−9.3 kcal/mol), 2 (ΔGb=−8.8 kcal/mol), and compound 3 (ΔGb=−9.0 kcal/mol) have a good binding energy score with an active pocket of protein inhibitor kinases. The outcomes of the current study showed that these compounds have anticancer action and might be used to create more potent drugs to treat melanoma, colon, and lung cancers.