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

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 (K-i = 0.53 mu M) exhibited equal inhibitory activities towards Mcl-1 protein compared to positive control gossypol (K-i = 0.39 mu M). This compound also possessed good antiproliferative activities against MDA-MB-231 and PC-3 cancer cells. (c) 2015 Elsevier Ltd. All rights reserved.