Discovery of novel vinyl sulfone derivatives as anti-tumor agents with microtubule polymerization inhibitory and vascular disrupting activities

Li, Wenlong; Yin, Ying; Yao, Hong; Shuai, Wen; Sun, Honghao; Xu, Shengtao; Liu, Jie; Yao, Hequan; Zhu, Zheying; Xu, Jinyi

Abstract

Vinyl sulfone or sulfoxide moieties were firstly introduced to the structure of chalcone compound by replacing the carbonyl group to afford a series of novel compounds as potential anti-tubulin agents. All of the target compounds were evaluated for their anti-proliferative activity. Among them, compound 12m showed the most potent activity against a panel of cancer cell lines with IC50 values ranging from 0.128 to 0.606??M. Further mechanism studies demonstrated that compound 12m caused G2/M phase arrest, induced cell apoptosis and disrupted the intracellular microtubule network. Moreover, compound 12m reduced the cell migration and disrupted the capillary-like tube formation in human umbilical vein endothelial cell (HUVEC) assays. Importantly, compound 12m significantly and dose dependently inhibited tumor growth in H22 liver cancer allograft mouse model, which is more potent than control compound CA-4, suggesting that 12m deserves further research as a potential anti-tubulin agent targeting colchicine binding site on tubulin.

Citation

Li, W., Yin, Y., Yao, H., Shuai, W., Sun, H., Xu, S., …Xu, J. (2018). Discovery of novel vinyl sulfone derivatives as anti-tumor agents with microtubule polymerization inhibitory and vascular disrupting activities. European Journal of Medicinal Chemistry, 157, 1068-1080. https://doi.org/10.1016/j.ejmech.2018.08.074

• Journal Article Type: Article
• Acceptance Date: Aug 26, 2018
• Online Publication Date: Aug 28, 2018
• Publication Date: Sep 5, 2018
• Deposit Date: Dec 5, 2018
• Journal: European Journal of Medicinal Chemistry
• Print ISSN: 0223-5234
• Electronic ISSN: 1768-3254
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 157
• Pages: 1068-1080
• DOI: https://doi.org/10.1016/j.ejmech.2018.08.074
• Keywords: Organic Chemistry; Pharmacology; Drug Discovery; General Medicine
• Public URL: https://nottingham-repository.worktribe.com/output/1370759
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0223523418307463
• Additional Information: This article is maintained by: Elsevier; Article Title: Discovery of novel vinyl sulfone derivatives as anti-tumor agents with microtubule polymerization inhibitory and vascular disrupting activities; Journal Title: European Journal of Medicinal Chemistry; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.ejmech.2018.08.074; Content Type: article; Copyright: © 2018 Elsevier Masson SAS. All rights reserved.