Activity and QSAR study of baogongteng A and its derivatives as muscarinic agonists

  • Bioorg Med Chem Lett. 2005 Nov 1;15(21):4814-8. doi: 10.1016/j.bmcl.2005.07.045.
Yin-Yao Niu  1 ,  Li-Min Yang ,  Hui-Zhong Liu ,  Yong-Yao Cui ,  Liang Zhu ,  Ju-Mei Feng ,  Jian-Hua Yao ,  Hong-Zhuan Chen ,  Bo-Tao Fan ,  Ze-Nai Chen ,  Yang Lu
Affiliations
  • 1. Institute of Materia Medica, Shanghai Second Medical University, Shanghai 200025, China.
PMID: 16153841 DOI: 10.1016/j.bmcl.2005.07.045
Abstract

Baogongteng A (BGT-A), a naturally occurring tropane muscarinic agonist isolated from Chinese medicinal plant, exhibits a bioactive effect different from those of many Tropane Alkaloids that are muscarinic antagonists. A series of racemic derivatives of BGT-A was synthesized to study the structure-activity relationships (SAR). To explore further the SAR in this series and to ultimately design muscarinic agonists for drug development, a Comparative Molecular Field Analysis (CoMFA) was performed. The values of the leave-one-out cross-validated correlation coefficient q2 and the conventional correlation coefficient r2 for the model are 0.613 and 0.965, respectively. The regression analysis of the data indicated that the steric effect of N-substituted group on tropane of analyzed compounds critically affected the agonistic activity to muscarinic receptors.

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