2-Anilino-3-Aroylquinolines as Potent Tubulin Polymerization Inhibitors

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• 作者：P. S. Srikanth ; V. Lakshma Nayak ; Korrapati Suresh Babu ; G. Bharath Kumar ; A. Ravikumar and Dr. Ahmed Kamal
• 刊名：ChemMedChem
• 出版年：2016
• 出版时间：September 20, 2016
• 年：2016
• 卷：11
• 期：18
• 页码：2050-2062
• 全文大小：2288K
• ISSN：1860-7187

文摘

Several 2-anilino-3-aroylquinolines were designed, synthesized, and screened for their cytotoxic activity against five human cancer cell lines: HeLa, DU-145, A549, MDA-MB-231, and MCF-7. Their IC₅₀ values ranged from 0.77 to 23.6 μm. Among the series, compounds 7 f [(4-fluorophenyl)(2-((4-fluorophenyl)amino)quinolin-3-yl)methanone] and 7 g [(4-chlorophenyl)(2-((4-fluorophenyl)amino)quinolin-3-yl)methanone] showed remarkable antiproliferative activity against human lung cancer and prostate cancer cell lines. The IC₅₀ values for inhibiting tubulin polymerization were 2.24 and 2.10 μm for compounds 7 f and 7 g, respectively, and were much lower than that of the reference compound E7010 [N-(2-(4-hydroxyphenylamino)pyridin-3-yl)-4-methoxybenzenesulfonamide]. Furthermore, flow cytometric analysis revealed that these compounds arrest the cell cycle at the G₂/M phase, leading to apoptosis. Apoptosis was also confirmed by mitochondrial membrane potential, Annexin V–FITC assay, and intracellular ROS generation. Immunohistochemistry, western blot, and tubulin polymerization assays showed that these compounds disrupt tubulin polymerization. Molecular docking studies revealed that these compounds bind efficiently to β-tubulin at the colchicine binding site.