Improved binding affinities of pyrrolidine derivatives as Mcl-1 inhibitors by modifying amino acid side chains |
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Authors: | Yichao Wan Tingting Liu Xiaoxian Li Chen Chen Hao Fang |
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Affiliation: | 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 |
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Abstract: | As an important member of anti-apoptotic Bcl-2 protein, myeloid cell leukemia sequence 1 (Mcl-1) protein is an attractive target for cancer therapy. In this study, a new series of pyrrolidine derivatives as Mcl-1 inhibitors were developed by mainly modifying the amino acid side chain of compound 1. Among them, compound 18 (Ki = 0.077 μM) exhibited better potent inhibitory activities towards Mcl-1 protein compared to positive control Gossypol (Ki = 0.18 μM). In addition, compound 40 possessed good antiproliferative activities against PC-3 cells (Ki = 8.45 μM), which was the same as positive control Gossypol (Ki = 7.54 μM). |
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Keywords: | Bcl-2 Mcl-1 Cancer Pyrrolidine Target |
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