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Use of Molecular Electrostatic Potentials for Analysis of Anticonvulsant Activities of Phenylsuccinimides

 

作者: W. Kwiatkowski,   J. Karolak-wojciechowska,  

 

期刊: SAR and QSAR in Environmental Research  (Taylor Available online 1993)
卷期: Volume 1, issue 2-3  

页码: 233-244

 

ISSN:1062-936X

 

年代: 1993

 

DOI:10.1080/10629369308028831

 

出版商: Taylor & Francis Group

 

关键词: anticonvulsants;conformational analysis;MNDO, ab initio;MEP

 

数据来源: Taylor

 

摘要:

The present study was performed on a group of 27 derivatives of phenylsuccinimides, of which only 12 were active against maximal electrical shock in spite of the structural similarities of these compounds. The work consisted of four main parts: 1. crystallographic investigations of a subset of chosen compounds; 2. conformational analysis of characteristic molecules from the investigated series, performed by means of molecular mechanics calculations; 3. molecular orbital optimization of all the molecules using the MNDO method starting with conformations obtained in 2; 4. molecular electrostatic potential (MEP) analysis which was performed on the semiempirical (MNDO) and ab initio levels. This research showed that MEP maps provide a signature that distinguishes between active and inactive compounds. There are MEP minima close to the two carbonyl oxygens of the imide ring, and although the magnitude of the difference between the two minima is approximately constant, the sign of the difference provides an activity index. The initial orientations of phenylsuccinimide molecules in relation to the receptor are not equivalent and they depend on the potential distribution around both the succinimide molecules and around the receptor. In the active compounds the negative potential difference at the discussed points most probably influences the initial set-up of the molecules in relation to the receptor and results in a considerably higher probability of the molecules being bound at the right place on the receptor.

 

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