Activity and QSAR study of baogongteng A and its derivatives as muscarinic agonists.
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.
Niu
Yin-Yao
YY
Institute of Materia Medica, Shanghai Second Medical University, Shanghai 200025, China.
Yang
Li-Min
LM
Liu
Hui-Zhong
HZ
Cui
Yong-Yao
YY
Zhu
Liang
L
Feng
Ju-Mei
JM
Yao
Jian-Hua
JH
Chen
Hong-Zhuan
HZ
Fan
Bo-Tao
BT
Chen
Ze-Nai
ZN
Lu
Yang
Y
D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000494:pharmacology; D006168:Guinea Pigs; D008958:Models, Molecular; D018721:Muscarinic Agonists / Q000138:chemical synthesis* / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000737:chemistry; D010936:Plant Extracts; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D011976:Receptors, Muscarinic / Q000737:chemistry / Q000378:metabolism; D014326:Tropanes / Q000138:chemical synthesis / Q000494:pharmacology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D018721:Muscarinic Agonists; D010936:Plant Extracts; D011976:Receptors, Muscarinic; D014326:Tropanes; C027863:bao gong teng A