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
  • 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: [email protected].
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.