新型Caspase-3抑制剂1,2–苯并异噻唑–3–酮–1,4–二取代–1,2,3–三唑类衍生物的合成

Synthesis of 1,2-benzisothiazol-3-one-derived 1,2,3-triazoles as a Novel Class of Caspase-3 Inhibitors

为探究对Caspase-3有更高抑制活性的非肽类小分子抑制剂,用"点击反应"合成了一系列1,2–苯并异噻唑–3–酮–1,4–二取代–1,2,3–三唑类衍生物.通过体外Caspase-3和Caspase-7抑制活性测试发现,化合物7c对Caspase-3有最好的抑制活性,IC50达到11.0±1.2,nmol/L.为了更好的理解这些化合物与Caspase-3蛋白的相互作用模式,进行了分子对接实验.结果表明,化合物7c与蛋白作用位点具有很好的结合模式,验证了该化合物具有很好的体外Caspase-3抑制活性.

In order to get a non-peptide inhibitor with higher inhibitory activities against caspase-3,a series of 1,2-benzisothiazol-3-one-derived 1,4-disubstituted 1,2,3-triazoles was prepared using the “click reaction” and evaluated as inhibitors against caspase-3,-7. The most potent caspase-3 inhibitor was found to be 7c with IC50-values of 11.0±1.2,nmol/L. Moreover,in order to better rationalize the action and the binding mode of these compounds,docking studies were carried out. The result suggests that there is good binding mode between 7c and caspase-3,protein.