2. Academic Validation
  3. Design, synthesis and preliminary biological studies of pyrrolidine derivatives as Mcl-1 inhibitors

Design, synthesis and preliminary biological studies of pyrrolidine derivatives as Mcl-1 inhibitors

  • Bioorg Med Chem. 2015 Dec 15;23(24):7685-93. doi: 10.1016/j.bmc.2015.11.014.
Yichao Wan 1,  Junhua Wang 2,  Feng'e Sun 1,  Minglu Chen 1,  Xuben Hou 1,  Hao Fang 3
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmacy, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, PR China.
  • 2 Institute of Agro-Food Science and Technology, Shandong Academy of Agricultural Sciences, Jinan, Shandong 250100, PR China.
  • 3 Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmacy, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, PR China. Electronic address: haofangcn@sdu.edu.cn.
PMID: 26620718 DOI: 10.1016/j.bmc.2015.11.014
Abstract

Anti-apoptotic proteins, such as B-cell lymphoma (Bcl-2) protein, myeloid cell leukemia sequence 1 (Mcl-1) protein, are potential targets for Cancer treatment. In the studies, a series of pyrrolidine derivatives were developed as potent Mcl-1 inhibitors. The preliminary biological studies suggested that most of target compounds exhibit good abilities for targeting Mcl-1 protein. Among them, compound 21 (Ki=0.53μM) exhibited equal inhibitory activities towards Mcl-1 protein compared to positive control gossypol (Ki=0.39μM). This compound also possessed good antiproliferative activities against MDA-MB-231 and PC-3 Cancer cells.

Keywords

Anti-tumor; Apoptosis; Bcl-2; Mcl-1; Pyrrolidine.

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