Combined Approach of QSAR and Docking Studies for the Design of Local Anaesthetic Agents

Abstract

Background: Heterocyclic scaffold, benzotriazole and its derivatives are potential anaesthetic agents that act locally.

Objective: QSAR and docking analysis of previously synthesized benzotriazolyl derivatives were modelled for their local anaesthetic action using computer assisted multiple regression analysis. It provides the insight about the structural requirements for the local anaesthetic action.

Method: A training set comprising of 16 molecules and test set of 8 molecules were selected for present investigation by using sphere exclusion method with dissimilarity value of +4.0. The validation of the QSAR models was performed by cross-validation and external test set prediction. Docking studies was performed using GRIP docking methodology.

Results & conclusion: Further GRIP docking with the pentameric ligand gated ion channel, 2XQ3 facilitated the mechanistic analysis of interactions of the test molecules active site residues.

Keywords: 2D-QSAR; GRIP docking; benzotriazolyl derivatives; heterocyclics; lead optimization; local anaesthetic agent.