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

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

Volume: 20 Issue: 3

Author(s): Chunyan Zhang*, Zhi Li, Jiahai Ma, Jing Zhang, Longming Zhang, Tao Li and Shijian Zheng*

Affiliation:

• Department of Anesthesiology, Yantai Yuhuangding Hospital, Affiliated Hospital of Medical College, Qingdao University, Shandong 264000,China

• Department of Anesthesiology, Yantai Yuhuangding Hospital, Affiliated Hospital of Medical College, Qingdao University, Shandong 264000,China

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

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.

Cite this article as:

Zhang Chunyan *, Li Zhi , Ma Jiahai , Zhang Jing , Zhang Longming , Li Tao and Zheng Shijian *, Combined Approach of QSAR and Docking Studies for the Design of Local Anaesthetic Agents, Combinatorial Chemistry & High Throughput Screening 2017; 20 (3) . https://dx.doi.org/10.2174/138620732003170803113816