Chen Fanglei, Zhang Guiping, Hong Zebin, Lin Zhonghui, Lei Min, Huang Mingdong, Hu Lihong
Shanghai Research Center for the Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, PR China.
Bioorg Med Chem Lett. 2014 May 15;24(10):2379-82. doi: 10.1016/j.bmcl.2014.03.045. Epub 2014 Mar 24.
The natural product embelin was found to have PAI-1 inhibitory activity with the IC50 value of 4.94μM. Based on the structure of embelin, a series of analogues were designed, synthesized, and evaluated for their ability to inhibit PAI-1. The SAR study on these compounds disclosed that the inhibitory potency largely depended on the hydroxyl groups at C2 and C5, and the length of the alkyl chains at C3 and C6. Compound 11 displayed the best PAI-1 inhibitory potency with the IC50 value of 0.18μM.
天然产物紫铆因被发现具有PAI-1抑制活性，IC50值为4.94μM。基于紫铆因的结构，设计、合成了一系列类似物，并对其抑制PAI-1的能力进行了评估。对这些化合物的构效关系研究表明，抑制效力很大程度上取决于C2和C5位的羟基以及C3和C6位烷基链的长度。化合物11表现出最佳的PAI-1抑制效力，IC50值为0.18μM。
