2. Academic Validation
  3. Design, synthesis and biological evaluation of novel pteridinone derivatives possessing a hydrazone moiety as potent PLK1 inhibitors

Design, synthesis and biological evaluation of novel pteridinone derivatives possessing a hydrazone moiety as potent PLK1 inhibitors

  • Bioorg Med Chem Lett. 2020 Aug 15;30(16):127329. doi: 10.1016/j.bmcl.2020.127329.
Zhiwei Li 1,  Le Xu 1,  Liangyu Zhu 1,  Yanfang Zhao 1,  Tao Hu 2,  Bixi Yin 2,  Yajing Liu 3,  Yunlei Hou 4
Affiliations

Affiliations

  • 1 School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.
  • 2 Yangtze River Pharmaceutical Group Pharmaceutical Co., Ltd, 1 South Yangtze River Road Taizhou, Jiangsu 225321, China.
  • 3 School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China. Electronic address: lyjpharm@126.com.
  • 4 School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China; Yangtze River Pharmaceutical Group Pharmaceutical Co., Ltd, 1 South Yangtze River Road Taizhou, Jiangsu 225321, China. Electronic address: houyunlei901202@163.com.
PMID: 32631534 DOI: 10.1016/j.bmcl.2020.127329
Abstract

A series of novel pteridinone derivatives possessing a hydrazone moiety were designed, synthesized and evaluated for their biological activity. Most of the synthesized compounds demonstrated moderate to excellent activity against A549, HCT116 and PC-3 Cancer cell lines. In particular, compound L19 exhibited the most potent antiproliferative effects on three cell lines with IC50 values of 3.23 μM, 4.36 μM and 8.20 μM, respectively. In kinase assays, the compound L19 also showed potent inhibition activity toward PLK1 with % inhibition values of 75.1. Further mechanism studies revealed that compound L19 significantly inhibited proliferation of HCT-116 cell lines, induced a great decrease in mitochondrial membrane potential resulting in Apoptosis of Cancer cells, inhibited the migration of tumor cells, and arrested G1 phase of HCT116 cells.

Keywords

Anti-cancer; PLK1; Pteridinone derivatives.

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