作用于神经系统药物的研究——Ⅲ、加锡果宁类似物构效关系的量子药理学研究

STUDIES ON POTENTIAL AGENTS ACTING ON NERVOUS SYSTEM——Ⅲ QUANTUM PHARMACOLOGY INVESTIGATION OF STRUCTURE-ACTIVITY RELATIONSHIPS OF EDULININE ANALOGUES

用Huckel分子轨道法计算了12个加锡果宁(Edulinine)类似物,并使用QSAR研究中的Hansch途径研究了它们对中枢神经系统抑制活性的各项药理指标与计算所获的分子轨道指数间的相关关系。结果表明生物活性仅与喹啉酮上2位羰基的碳氧两个原子的亲电超离域度之和S_C^E=O与3、4位双键的两个碳原子的亲电超离城变之和S_C^E有良好的线性关系。这表明加锡果宁类似物与受体作用机制可能是一个亲电作用过程。

Edulinine is one of the active ingredients isolated from Chinese herb Zanthoxylum Simulans Hance which is widely distributed in China. According to the pharmacological and preliminary clinical tests, edulinine and its analogues have potent activities on central nervous system. Attempts were made to study the quantum pharmacology through Huckel Molecular ordital and Hansch approach. We caculated 12 edulinine analogues and obtained various molecular orbital ndices, isuch as E_(HOMO), E_(LUMO), bond order el- ectron density net charge, frontal orbital index etc. The following equation was derived by the regression of such data: log1/C=2. 485-1. 501(+0.259) S_C^E=0+ 2.777(+0.357) S_C^E=C n=11; r=0.942; S=0.105; F=31.56 where 1/e represents anticovulsive activ- ity, S_C^E=0 is the sum of electrophilic superdelocalizability of carbonylcarbon a- nd oxygen atoms of quionlinones: S_CE=C is the sum of electrophilic superdelocali- zability of α, β carbon atoms by the ca- rbonyl group. As a result of regression analys, we suggest that the mechanism of edulinine analogues-receptor complex my be a electrophilic process.