2. Academic Validation
  3. Discovery of novel vinyl sulfone derivatives as anti-tumor agents with microtubule polymerization inhibitory and vascular disrupting activities

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

  • Eur J Med Chem. 2018 Sep 5:157:1068-1080. doi: 10.1016/j.ejmech.2018.08.074.
Wenlong Li 1,  Ying Yin 1,  Hong Yao 1,  Wen Shuai 1,  Honghao Sun 1,  Shengtao Xu 2,  Jie Liu 3,  Hequan Yao 1,  Zheying Zhu 4,  Jinyi Xu 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, PR China.
  • 2 State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, PR China. Electronic address: cpuxst@163.com.
  • 3 Department of Organic Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, PR China; State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, and School of Chemistry and Pharmacy, Guangxi Normal University, Guilin, 541004, China.
  • 4 Division of Molecular Therapeutics & Formulation, School of Pharmacy, The University of Nottingham, University Park Campus, Nottingham, NG7 2RD, UK.
  • 5 State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, PR China. Electronic address: jinyixu@china.com.
PMID: 30176537 DOI: 10.1016/j.ejmech.2018.08.074
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 μM. 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.

Keywords

Anti-tumor activity; Colchicine binding site; Tubulin inhibitors; Vinyl sulfone.

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