2. Academic Validation
  3. Design, synthesis and biological evaluation of hydantoin derivatives as Mcl-1 selective inhibitors

Design, synthesis and biological evaluation of hydantoin derivatives as Mcl-1 selective inhibitors

  • Bioorg Chem. 2022 Apr;121:105643. doi: 10.1016/j.bioorg.2022.105643.
Xiao Liang 1,  Xue Li 2,  Zhiyuan Zhao 1,  Yiming Nie 1,  Zefu Yao 1,  Wandi Ren 3,  Xinying Yang 3,  Xuben Hou 4,  Hao Fang 5
Affiliations

Affiliations

  • 1 Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Science, Cheeloo College of Medicine, Shandong University, Ji'nan, Shandong 250012, PR China.
  • 2 Institute of Immunopharmaceutical Sciences, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, PR China.
  • 3 Department of Pharmaceutical Analysis, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Ji'nan, Shandong 250012, PR China.
  • 4 Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Science, Cheeloo College of Medicine, Shandong University, Ji'nan, Shandong 250012, PR China. Electronic address: hxb@sdu.edu.cn.
  • 5 Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Science, Cheeloo College of Medicine, Shandong University, Ji'nan, Shandong 250012, PR China. Electronic address: haofangcn@sdu.edu.cn.
PMID: 35150958 DOI: 10.1016/j.bioorg.2022.105643
Abstract

As a member of Bcl-2 protein family, myeloid cell leukemia-1 (Mcl-1) plays a critical role in cell Apoptosis and has become a promising anti-cancer drug target. Herein, we designed and synthesized a series of hydantoin derivatives as novel Mcl-1 inhibitors based on our previously developed lead compound. Among them, compound M23 and M24 exhibited good binding affinities against Mcl-1 with Ki values of 0.49 μM and 0.33 μM respectively. Especially, compound M23 exhibited good selectivity over Bcl-xL, whereas compound M24 possessed good selectivity over both Bcl-2 and Bcl-xL. Furthermore, we also investigated the effects of these new Mcl-1 inhibitors on cell proliferation, Apoptosis and mitochondrial membrane potential, as well as the stability in plasma.

Keywords

Apoptosis; Cancer; Hydantoin derivatives; Mcl-1 inhibitors.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-115928
    Mcl-1抑制剂
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