Synthesis and antiproliferative activity of 2-aryl-4-(3, 4, 5-trimethoxybenzoyl)-1, 2, 3-triazol derivatives as microtubule-destabilizing agents. Issue 46 (5th June 2017)

• Record Type: Journal Article
• Authors: Feng, Dongjie; Wu, Yue; Wang, Hao; Bai, Zhaoshi; Wang, Defa; Zuo, Daiying; Bao, Kai; Wu, Yingliang; Zhang, Weige
• Is Part Of: RSC advances. Volume 7:Issue 46(2017)
• Page Start: 29103
• Page End: 29111
• Publication Date: 2017-06-05
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c7ra02720f
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : A series of 2-aryl-4-(3, 4, 5-trimethoxybenzoyl)-1, 2, 3-triazols were designed as analogs of substituted methoxybenzoyl-aryl-thiazole (SMART) under the consideration of geometric features. Abstract : A series of 2-aryl-4-(3, 4, 5-trimethoxybenzoyl)-1, 2, 3-triazols were designed as analogs of substituted methoxybenzoyl-aryl-thiazole (SMART) under the consideration of geometric features. The target compounds were synthesized via concise and efficient processes including microwave-assisted cyclization, and were evaluated for their antiproliferative activity against three human cancer cell lines. Most compounds exhibited moderate antiproliferative activity with IC50 values in the micromolar to sub-micromolar range. Tubulin polymerization and immunofluorescence studies demonstrated that( Z )-9a was a potent microtubule-destabilizing agent and disrupted the polymerization dynamics. Moreover, ( Z )-9a significantly induced accumulation of cells in the G2/M phase and caused microtubule destabilization. Molecular modeling studies showed that( Z )-9a probably binds to the colchicine site of tubulin.