Xu Guangsen, Liu Tingting, Zhou Yi, Yang Xinying, Fang Hao
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.
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.
Bioorg Med Chem. 2017 Oct 15;25(20):5548-5556. doi: 10.1016/j.bmc.2017.08.024. Epub 2017 Aug 15.
Bcl-2 proteins, such as B-cell lymphoma (Bcl-2) protein, myeloid cell leukemia sequence 1 (Mcl-1) protein, has been implicated in the progression and survival of multiple tumor types and become a validated and attractive target for cancer therapy. In this work, a series of 1-phenyl-1H-indole derivatives has been designed and synthesized. The preliminary biological studies (binding assay for Bcl-2 proteins and MTT assay) suggested that some active compounds showed potent inhibitory activities on Bcl-2/Mcl-1 without binding on Bcl-X Furthermore, Compound 9c and 9h showed better anti-proliferative activity than WL-276.
Bcl-2蛋白，如B细胞淋巴瘤（Bcl-2）蛋白、髓样细胞白血病序列1（Mcl-1）蛋白，与多种肿瘤类型的进展和存活有关，已成为癌症治疗中一个经过验证且具有吸引力的靶点。在这项工作中，设计并合成了一系列1-苯基-1H-吲哚衍生物。初步生物学研究（Bcl-2蛋白结合测定和MTT测定）表明，一些活性化合物对Bcl-2/Mcl-1具有强效抑制活性，而不与Bcl-X结合。此外，化合物9c和9h显示出比WL-276更好的抗增殖活性。
