2‐Anilino‐3‐Aroylquinolines as Potent Tubulin Polymerization Inhibitors. (28th July 2016)

• Record Type: Journal Article
• Authors: Srikanth, P. S.; Nayak, V. Lakshma; Suresh Babu, Korrapati; Kumar, G. Bharath; Ravikumar, A.; Kamal, Ahmed
• Is Part Of: ChemMedChem. Volume 11:Number 18(2016)
• Page Start: 2050
• Page End: 2062
• Publication Date: 2016-07-28
• Subjects: antitumor agents -- apoptosis -- cell cycle -- colchicine -- tubulin; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201600259
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract: 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, compounds7 f [(4‐fluorophenyl)(2‐((4‐fluorophenyl)amino)quinolin‐3‐yl)methanone] and7 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 compounds7 f and7 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. Abstract : A red light for cell division : A new series of 2‐anilino‐3‐aroylquinolines were synthesized and evaluated for their anticancer activity. Tubulin polymerization assays, western blot analyses, Annexin V–FITC assays, analysis of intracellular ROS generation, and immunohistochemistry data indicate that these compounds effectively disrupt tubulin polymerization by interacting with the colchicine binding site of tubulin.