Synthesis, biological evaluation and molecular docking studies of aminochalcone derivatives as potential anticancer agents by targeting tubulin colchicine binding site

• Published in: Bioorganic chemistry Vol. 78; pp. 332 - 340
• Main Authors: Wang, Guangcheng, Peng, Zhiyun, Zhang, Jiebing, Qiu, Jie, Xie, Zhenzhen, Gong, Zipeng
• Format: Journal Article
• Language: English
• Published: SAN DIEGO Elsevier Inc 01.08.2018; Elsevier
• Subjects: Anticancer activity; Biochemistry & Molecular Biology; Chalcone; Chemistry; Chemistry, Organic; Claisen-Schmidt condensation; Life Sciences & Biomedicine; Naphthalene; Physical Sciences; Science & Technology; Tubulin; Tubulin; Naphthalene; Claisen-Schmidt condensation; Chalcone; Anticancer activity; DESIGN; ACID; ANALOGS; ANTITUBULIN; COMBRETASTATIN A-4; MICROTUBULE DYNAMICS; CHALCONE DERIVATIVES; MILLEPACHINE DERIVATIVES; ANTIMITOTIC CHALCONES; INHIBITORS
• ISSN: 0045-2068; 1090-2120; 1090-2120
• DOI: 10.1016/j.bioorg.2018.03.028

[Display omitted] •A novel series of aminochalcone derivatives were designed and synthesized.•In vitro anticancer activities were determined.•Compound 4 was found to be the most active compound.•Compound 4 inhibited tubulin polymerization and induced cell cycle arrest.•Molecular docking study was carried out. A series of aminochalcone derivatives have been synthesized, characterized by HRMS, 1H NMR and 13C NMR and evaluated for their antiproliferative activity against HepG2 and HCT116 human cancer cell lines. The most of new synthesized compounds displayed moderate to potent antiproliferative activity against test cancer cell lines. Among the derivatives, compound 4 displayed potent inhibitory activity with IC50 values ranged from 0.018 to 5.33 μM against all tested cancer cell lines including drug resistant HCT-8/T. Furthermore, this compound showed low cytotoxicity on normal human cell lines (LO2). The in vitro tubulin polymerization assay showed that compound 4 inhibited tubulin assembly in a concentration-dependent manner with IC50 value of 7.1 μM, when compared to standard colchicine (IC50 = 9.0 μM). Further biological evaluations revealed that compound 4 was able to arrest the cell cycle in G2/M phase. Molecular docking study demonstrated the interaction of compound 4 at the colchicine binding site of tubulin. All the results indicated that compound 4 is a promising inhibitor of tubulin polymerization for the treatment of cancer.