Identification of pentacyclic triterpenes derivatives as potent inhibitors against glycogen phosphorylase based on 3D-QSAR studies

作者：Liang Zhongjie; Zhang Liying; Li Lianchun; Liu Jun; Li Hongling; Zhang Luyong; Chen Limin; Cheng Keguang; Zheng Mingyue; Wen Xiaoan; Zhang Pu; Hao Jia; Gong Yanchun; Zhang Xia; Zhu Xiaoyun; Chen Jun; Liu Hong; Jiang Hualiang; Luo Cheng^*; Sun Hongbin

来源：European Journal of Medicinal Chemistry, 2011, 46(6): 2011-2021.

DOI：10.1016/j.ejmech.2011.02.053

• 3D-QSAR
• Pentacyclic triterpenes
• Glycogen phosphorylase

Naturally occurring pentacyclic triterpenes (PT), a novel class of inhibitors against glycogen phosphorylase (GP), hold promise for the treatment of type-2 diabetes and other diseases with disorders in glycogen metabolism. To identify novel and more potent GP inhibitors, the receptor-based comparative molecular field analysis (CoMFA) and comparative molecular similarity analysis (CoMSIA) approaches were performed to investigate the quantitative structure activity relationships (QSAR) among 106 PT analogues. The validated models demonstrated that the elongated or bulky substitutions in C17 position and/or C2, C3 positions are favorable. Then based on the structural information extracted from these models, 56 derivatives were synthesized and biochemically tested in this study. The IC(50) value of the most potent compound P50 was found to be 1.1 mu M.

• 单位
  中国科学院上海药物研究所; 中国药科大学; 苏州大学; 东华大学