A geometry optimization and molecular electrostatic potential mapping study of structure-activity relationship for some anti-Alzheimer agents

Abstract

<span style="font-size:12.0pt;font-family: " times="" new="" roman";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-in;mso-fareast-language:en-in;mso-bidi-language:ar-sa"="" lang="EN-IN">Molecular geometries of some substituted (pyrroloamino)pyridines which possess anti-Alzheimer activity were optimized and potential-derived CHelpG point charges were computed using <i>ab initio </i>SCF molecular orbital approach employing the 3-21 G basis set. AM I molecular orbital calculations were performed using these optimized geometries and thus optimized Hybridization Displacement Charges (HOC) combined with Lowdin charges continuously distributed in three dimension were obtained. Molecular electrostatic potential (MEP) maps of the molecules were obtained in two ways: (i) using the HOC-based model with the help of which MEP minima near the molecules were located, and (ii) using the CHelpG point charges, MEP values on the van der Waals surfaces of the molecules were computed. The MEP maps computed using both the methods have negative MEP regions near the pyridine nitrogen atom which appears to be the main binding site of the molecules with the appropriate receptor. Both electrostatic interaction and lipophilic association between these molecules and the receptor appear to contribute to biological activity.</span>