Design, synthesis and biological evaluation of 4-amino-quinolines as antitumor agents

Fifteen novel 4-amino-quinolines (I1-III3) as antitumor agent were synthesized by p-nitroaniline and ethoxymethylene malonic ester (EMME) via condensation, cyclization, hydrolysis, decarboxylation, chlorination, nucleophilic substitution, reduction and amidation. The antitumor activity of compounds I₁-III₃ was evaluated on SGC-7901, BEL-7402 and A549 cancer cell lines. In vitro bioassay indicated that some compounds showed different degree activity against all tested cancer cell lines. Compound I₁, I₄ and II₂ exhibited high effects against A549 cell lines (IC₅₀ = 1.34μM, 1.36μM and 3.00μM, respectively). In addition, the result of molecular docking showed that compound I₁, I₄ and II₂ could dock into the pocket of EGFR.