Synthesis, docking, and cytotoxic activities of novel 2-aryl-4-(arylamino)quinazolines

Abstract

A synthesis of functionalized 2-aryl-4-(arylamino)quinazolines from 4-chloro-2-arylquinazolines (derived from 2-arylquinazolin-4(3H)-one) and 5-chloroaniline derivatives in DMF is described. The interaction of 2-aryl-4-(arylamino)quinazolines with their biological target, human epithelial growth factor receptor (EGFR), was investigated by molecular docking. Docking results indicated lower binding energy for all compounds towards EGFR active sites. The cytotoxic activities of fifteen 2-aryl-4-(arylamino)quinazolines are evaluated against lung adenocarcinoma (A549) and ovarian cancer (SKOV3) cell lines using MTT method. Our results demonstrated that among the tested compounds 2-(4-bromophenyl)-N-(5-chloro-2-methylphenyl)quinazolin-4-amine and N-(2,5-dichlorophenyl)-2-(4-chlorophenyl)quinazolin-4-amine showed desirable cytotoxic activities on both cell lines. Compounds 2-(3-bromophenyl)-N-(5-chloro-2-methylphenyl)quinazolin-4-amine and 2-(4-bromophenyl)-N-(2,5-dichlorophenyl)quinazolin-4-amine displayed appropriate cytotoxic activities on A549 and SKOV3 cell lines, respectively.