New substituted quinazoline analogs: Synthesis, anticancer evaluation and docking study

Abstract

In this work, fifteen new substituted quinazoline analogs were synthesized in good yields through the reaction of 7-(2-chloroethoxy)-6-methoxy-N-arylquinazoline-4-amine and secondary amines such as dimethylamine, pyrrolidine, and piperidine.MTT method was used to evaluate the cytotoxicity of all synthesized substituted quinazolines on HU02 (foreskin fibroblast) and A431 (human carcinoma cell) cell lines. With the help of molecular docking, the binding mode between EGFR and the most effective compound 3f was investigated and analyzed. The results showed that at a concentration of less than 100 µM, the growth of A431 cells could be inhibited by the most effective synthesized compounds. Compared to Erlotinib as positive control, the highest cytotoxic property with IC50 equal to 1.21 µM belonged to compound 3f carrying piperidine with 3-chloroaniline.Cytotoxicity against HU02 cell line was not favorable in all synthesized compounds. Compared to Erlotinib, the hydrogen bond distance of quinazoline N1 of the compound with the Met-769 residue of EGFR (1.071 Å) is smaller, indicating greater cytotoxicity of this compound. The reasons for the stronger 3f can be most likely attributed to the two phenomena of greater lipophilicity and flexibility of piperidine.