Abstract

QSAR rationales for the 5-HT6 antagonistic activity of Epiminocyclohepta[b]indoles

Author(s): Manju Choudhary and Brij Kishore Sharma

The 5-HT6 receptor binding affinities of the epiminocyclohepta[b]indole derivatives have been quantitatively expressed in terms of topological and molecular features. The analysis revealed that more number of rings (nBnz, nCIC and nR05) and lesser number of rotatable bonds (RBN) in molecular structure are advantageous to improve 5-HT6 receptor binding affinity. A higher value of the molecular topology and symmetry accounting parameters (SIC4, structural information content of 3-order neighborhood symmetry and IC5, information content index of 5- order neighborhood symmetry) is favorable to the activity. A lower value of atomic polarizabilities associated to path length 8 of the Geary autocorrelation (GATS8p) and more hydrophobicity of molecule (MLOGP) are favorable to activity. Presence or absence of certain structural fragments X- -CH..X (descriptor C-033), R- - N- -R or R- -N- - X (descriptor N-075) and more number of hydrogen atoms attached to sp or sp2 or sp3 hybridized carbon atoms (H- 047) in a molecular structure are also relevant for the binding affinity. The derived models and participating descriptors in them have suggested that the substituents of epiminocyclohepta[b]indole moiety have sufficient scope for further modification.

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