Design, synthesis and molecular modeling of new quinoline analogues as potential anti-cancer agents

Abstract A series of novel 3-Phenyltrifluoromethyl quinoline derivatives were designed, synthesized and evaluated for anti-cancer activity. The synthesis of target mixtures was achieved by cyclization reaction by means of aromatic aldehydes and amines. The in vitro anticancer activity was evaluated by SRB assay (sulforhodamine B) against b MCF-7 breast cell line. Ko (synthesized compound) showed the maximum anti-cancer action on particularly breast cancer cell line. The SAR study exposed that phenyl group with electronegative group on R position of 3-phenyltrifluoromethyl quinoline ring exhibited important growth inhibitory action. Studies of molecular modeling revealed that Kl, Ko, and Kh, compounds showed the interaction of H- bond with amino acid residues SER217, HIS116, SER117, THR151, TYR199, and LYS221 of PDB ID: 1UOU (thymidine phosphorylase). The present study also showed that the addition of electron pulling groups on 5th position of 3-phenyltrifluoromethyl quinoline are responsible for better anti-cancer activity.