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 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 +/- 0.05 mu M) by binding in to the active pocket of EGFR receptor with minimum binding energy (Delta G(b) = -58.3691 kcal/mol). The binding was stabilized by two hydrogen bonds, two pi-cation and one pi-sigma interactions. Compound 5d showed most effective inhibition (IC50 = 0.37 +/- 0.04 mu M). (c) 2014 Elsevier Ltd. All rights reserved.