State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
Bioorg Med Chem. 2011 Nov 1;19(21):6518-24. doi: 10.1016/j.bmc.2011.08.013. Epub 2011 Aug 16.
In present study, a series of new 1,3,4-oxadiazole derivatives containing 1,4-benzodioxan moiety (6a-6s) as potential telomerase inhibitors were synthesized. The bioassay tests demonstrated that compounds 6k, 6l, 6m, 6n and 6s exhibited broad-spectrum antitumor activity with IC(50) concentration range from 7.21 μM to 25.87 μM against the four cancer cell lines, HEPG2, HELA, SW1116 and BGC823. Moreover, all the title compounds were assayed for telomerase inhibition using the TRAP-PCR-ELISA assay. The results showed compound 6k possessed the most potent telomerase activity (IC(50)=1.27 ± 0.05 μM). Docking simulation was performed to position compound 6k into the active site of telomerase (3DU6) to determine the probable binding model.
在本研究中，合成了一系列含有 1,4-苯并二恶烷结构的新型 1,3,4-噁二唑衍生物（6a-6s）作为潜在的端粒酶抑制剂。生物测定试验表明，化合物 6k、6l、6m、6n 和 6s 对四种癌细胞系 HEPG2、HELA、SW1116 和 BGC823 表现出广谱抗肿瘤活性，IC50 浓度范围为 7.21 μM 至 25.87 μM。此外，还使用 TRAP-PCR-ELISA 测定法对所有标题化合物进行了端粒酶抑制测定。结果表明，化合物 6k 具有最强的端粒酶活性（IC50=1.27±0.05 μM）。进行了对接模拟，将化合物 6k 定位到端粒酶（3DU6）的活性部位，以确定可能的结合模型。
