Schiff’s base derivatives bearing nitroimidazole and quinoline nuclei: New class of anticancer agents and potential EGFR tyrosine kinase inhibitors

New Schiff’s base derivatives 5a–j have been synthesized by reaction between 2-phenoxyquinoline-3-carbaldehydes and 2-(2-methyl-5-nitro-1H-imidazol-1-yl)acetohydrazide in presence of nickel(II) nitrate as a catalyst in ethanol under reflux in good yield (78–92%). All compounds were tested for anticancer and inhibition of EGFR. Of the compounds studied, majority of the compounds showed effective antiproliferation and inhibition of EGFR activities. Compound 5h showed most effective inhibition (IC50=0.12±0.05μM) by binding in to the active pocket of EGFR receptor with minimum binding energy (ΔGb=−58.3691kcal/mol). The binding was stabilized by two hydrogen bonds, two π–cation and one π–sigma interactions. Compound 5d showed most effective inhibition (IC50=0.37±0.04μM) against HER-2. New Schiff’s base derivatives 5a–j have been synthesized by reaction between 2-phenoxyquinoline-3-carbaldehydes 3a–j and 2-(2-methyl-5-nitro-1H-imidazol-1-yl)acetohydrazide 4 in presence of nickel(II) nitrate as a catalyst in ethanol under reflux in good yield (78–92%). All compounds were tested for anticancer and inhibition of EGFR. Of the compounds studied, majority of the compounds showed effective antiproliferation and inhibition of EGFR and HER-2 activities. Compound 5h showed most effective inhibition (IC50=0.12±0.05μM) by binding in to the active pocket of EGFR receptor with minimum binding energy (ΔGb=−58.3691kcal/mol). The binding was stabilized by two hydrogen bonds, two π–cation and one π–sigma interactions. Compound 5d showed most effective inhibition (IC50=0.37±0.04μM).