IN-SILICO STUDY OF ARYL SULPHONAMIDES AS 5-HT6 SEROTONIN LIGAND: A 2D QSAR STUDY USING TOPOLOGICAL DESCRIPTORS

Serotonin plays a crucial role in various cognitive and behavioral functions. The serotonin signaling is mediated by binding of serotonin to specific receptors on the cell surface. Serotonin 5-HT₆ receptors turned out to be promising biological targets for the modulation of central nervous system dysfunctions. Several classes of serotonin 5-HT₆ receptor ligands have been discovered. Among them, many aryl sulphonamides derivatives as 5-HT₆ antagonists were reported to have better affinity towards the receptor. In the present study, a quantitative structure-activity relationship (QSAR) study of forty derivatives of aryl sulphonamide and sulfone based 5-HT₆antagonists has been made with the help of topological parameters. The descriptors that have been used are valence connectivity indices of order 0, 1 & 2 and shape indices of order 1, 2 & 3. The biological activities of compounds have been taken from the literature. The study indicates that the valence connectivity index (order-0) appears an important descriptor for the QSAR study of aryl sulphonamides which alone gives a QSAR model with reliable predictive power. The best combination of descriptors obtained for this study is valence connectivity index (order-0), shape index (order-1) and shape index (order-2). The predicted activities obtained from this QSAR model are very close to observed activities. This QSAR model can be used to find the activity of any new derivative of aryl sulphonamides.