A novel series of indazole tethered oxadiazoles (OTDs) derivatives were synthesized, characterized and screened for their anti-proliferative activity against hepatocellular carcinoma (HCC) cells. OTDs structure was further confirmed by Single-crystal X-ray diffraction studies. Among the tested OTDs, compound 2-(4-methoxyphenyl)-5-(1-methyl-1H-indazol-3-yl)-1,3,4-oxadiazole was found to inhibit the catalytical activity of SIRT2 and brings about apoptosis as shown by western blot analysis and flow cytometry data. Also, the tested OTDs were found to interact with the active site of human SIRT2 in silico but not with the cavity of co-crystal ligand 5-(3- hydroxypropyl)-3-(4-chlorophenyl)-1,2,4-oxadiazole, which indicate that these OTDs has potential in the development of SIRT2 inhibitors in liver cancer models.

合成，表征和筛选了一系列新型的吲唑系氧杂二唑（OTDs）衍生物，它们针对肝细胞癌（HCC）细胞具有抗增殖活性。通过单晶X射线衍射研究进一步证实了OTD的结构。在测试的OTD中，发现化合物2-（4-甲氧基苯基）-5-（1-甲基-1H-吲唑-3-基）-1,3,4-恶二唑抑制SIRT2的催化活性并导致细胞凋亡如蛋白质印迹分析和流式细胞仪数据所示。而且，发现测试的OTD在计算机中与人SIRT2的活性位点相互作用，但与共结晶配体5-（3-羟丙基）-3-（4-氯苯基）-1,2,4-的空腔不相互作用。恶二唑，表明这些OTD在肝癌模型中具有开发SIRT2抑制剂的潜力。