Design, synthesis and biological evaluation of new 4-(4-substituted-anilino)quinoline derivatives as anticancer agents

A new series of 4-(4-substituted-anilino)quinoline derivatives 6a–f was synthesized from amine derivatives via Gould–Jacobs reaction. All synthesized compounds were evaluated for their cytotoxic activity against two human cancer cell lines; breast carcinoma (MCF-7) and non-small cell lung cancer (A549). The tested compounds showed a broad range of activities (IC₅₀ = 3.42–23.32 and 5.97–22.01 µM) in comparison with doxorubicin (IC₅₀ = 2.07 and 0.02 µM) and erlotinib (IC₅₀ = 1.14 and 19.26 µM) for MCF-7 and A549 respectively. The 4-(4-chloroanilino)quinoline derivative (6c, IC₅₀ = 3.42 and 5.97 µM) was the most potent among all compounds against both MCF-7 and A549 cell lines respectively. In addition, molecular docking studies were performed and the results were in agreement with the in vitro cytotoxic data.