Bioorganic & Medicinal Chemistry ( IF 3.3 ) Pub Date : 2017-08-15 , DOI: 10.1016/j.bmc.2017.08.024 Guangsen Xu , Tingting Liu , Yi Zhou , Xinying Yang , Hao Fang
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-XL. Furthermore, Compound 9c and 9h showed better anti-proliferative activity than WL-276.
中文翻译:
1-苯基-1 H-吲哚衍生物作为新型的Bcl-2 / Mcl-1双重抑制剂:设计,合成和初步生物学评估
Bcl-2蛋白,例如B细胞淋巴瘤(Bcl-2)蛋白,髓样细胞白血病序列1(Mcl-1)蛋白,已牵涉多种肿瘤类型的进展和存活,并成为经验证且有吸引力的靶标癌症治疗。在这项工作中,已经设计并合成了一系列的1-苯基-1 H-吲哚衍生物。初步的生物学研究(Bcl-2蛋白的结合测定和MTT测定)表明,某些活性化合物对Bcl-2 / Mcl-1表现出有效的抑制活性,而对Bcl-XL不起约束作用。此外,化合物9c和9h显示出更好的抗-增殖活性高于WL-276。