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.
复制标题
DOI：
10.1016/j.bmc.2015.11.014
复制
发表时间：
2015-12
影响因子：
3.5
通讯作者：
Yichao Wan;Junhua Wang;F. Sun;Ming-Dian Chen;Xuben Hou;H. Fang
中科院分区：
文献类型：
--
作者：
Yichao Wan;Junhua Wang;F. Sun;Ming-Dian Chen;Xuben Hou;H. Fang
抗凋亡蛋白，如b细胞淋巴瘤（Bcl-2）蛋白，髓细胞白血病序列1 （Mcl-1）蛋白，是癌症治疗的潜在靶点。在研究中，一系列吡咯烷衍生物被开发为有效的Mcl-1抑制剂。初步的生物学研究表明，大多数靶化合物对Mcl-1蛋白具有良好的靶向能力。其中化合物21（Ki= 0.53 μM）对Mcl-1蛋白的抑制活性与阳性对照棉酚（Ki= 0.39 μM）相当。该化合物对MDA-MB-231和PC-3癌细胞也具有良好的抗增殖活性。
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(Ki= 0.53 μM) exhibited equal inhibitory activities towards Mcl-1 protein compared to positive control gossypol (Ki= 0.39 μM). This compound also possessed good antiproliferative activities against MDA-MB-231 and PC-3 cancer cells.