2. Academic Validation
  3. Design, synthesis, and biological activity evaluation of novel tubulin polymerization inhibitors based on pyrimidine ring skeletons

Design, synthesis, and biological activity evaluation of novel tubulin polymerization inhibitors based on pyrimidine ring skeletons

  • Bioorg Med Chem Lett. 2023 Mar 15:84:129195. doi: 10.1016/j.bmcl.2023.129195.
Yingying Kang 1,  Yuanyuan Pei 1,  Jinling Qin 1,  Yixin Zhang 1,  Yongtao Duan 2,  Hua Yang 1,  Yongfang Yao 3,  Moran Sun 4
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, and Institute of Drug Discovery & Development, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, China.
  • 2 Henan Provincial Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou University, Zhengzhou 450018, China.
  • 3 School of Pharmaceutical Sciences, and Institute of Drug Discovery & Development, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, China. Electronic address: [email protected].
  • 4 School of Pharmaceutical Sciences, and Institute of Drug Discovery & Development, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, China. Electronic address: [email protected].
PMID: 36828299 DOI: 10.1016/j.bmcl.2023.129195
Abstract

A library of new pyrimidine analogs was designed and synthesized of these, compound K10 bearing a 1,4‑benzodioxane moiety and 3,4,5‑trimethoxyphenyl group, exhibiting the most potent activity, with IC50 values of 0.07-0.80 μM against four Cancer cell lines. Cellular-based mechanism studies elucidated that K10 inhibited microtubule polymerization, blocked the cell cycle at the G2/M phase, and eventually induced Apoptosis of HepG2 cells. Additionally, K10 inhibited the migration and invasion of HepG2 cells in a dose-dependent manner. Overall, our work indicates that the tubulin polymerization inhibitor incorporating pyrimidine and the 3,4,5‑trimethoxyphenyl ring may deserve consideration for Cancer therapy.

Keywords

Antitumor; Colchicine site; Pyrimidine; Tubulin; Tubulin inhibitors.

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