Synthesis of biological potent novel 3-(3,5-bis(trifluoromethyl) phenyl)-N-aryl-1,8-naphthyridine derivatives and in vitro antimicrobial, and anticancer activity

Abstract

A straight forward and efficient green method has been outlined for the construction of 3-(3,5-bis(trifluoromethyl)phenyl)-N-aryl-1,8-naphthyridin-2-amines in the presence of [Pd(PPh₃)₄] catalyst accomplished excellent yields in short reaction time. The compounds exhibited strongest antibacterial activity against pathogenic cell lines Staphylococcus aureus (22.5 mm, 35.5 mm), Escherichia coli (31.5 mm, 37.5 mm), and antifungal cell lines Candida albicans (35.5 mm, 35 mm), Aspergillus Niger (38.5 mm, 41.5 mm) compared with clinical drugs. Anticancer activity was conducted against cancer cell lines (breast (MCF7), SiHa (human cervix cancer cell line), and A549 cells (lung carcinoma epithelial cells). Results showed that the compounds 8h, 8d and 8i are most cytotoxic to all three cancer cell lines. IC₅₀ valves of these molecules exhibited significant activity against cancer cell lines MCF7 (13.45 ± 0.06, 15.20 ± 0.04), SiHa (14.32 ± 0.48, 18.25 ± 0.36), and A549 (16.23 ± 0.41, 18.26 ± 0.11). To further understand molecular docking studies were conducted. The docking scores suggested strong binding affinities, and specificity for c-Met target protein.