Design, synthesis and preliminary biological studies of pyrrolidine derivatives as Mcl-1 inhibitors. Issue 24 (15th December 2015)

• Record Type: Journal Article
• Authors: Wan, Yichao; Wang, Junhua; Sun, Feng'e; Chen, Minglu; Hou, Xuben; Fang, Hao
• Is Part Of: Bioorganic & medicinal chemistry. Volume 23:Issue 24(2015)
• Page Start: 7685
• Page End: 7693
• Publication Date: 2015-12-15
• Subjects: Apoptosis -- Bcl-2 -- Mcl-1 -- Pyrrolidine -- Anti-tumor; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2015.11.014
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: 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, compound21 ( K i = 0.53 μM) exhibited equal inhibitory activities towards Mcl-1 protein compared to positive control gossypol ( K i = 0.39 μM). This compound also possessed good antiproliferative activities against MDA-MB-231 and PC-3 cancer cells.