3D-QSAR and docking studies on adenosine A_2A receptor antagonists by the CoMFA method

Abstract

Parkinson’s disease affects millions of people around the world. Recently, adenosine A_2A receptor antagonists have been identified as a drug target for the treatment of Parkinson’s disease. Consequently, there is an immediate need to develop new classes of A_2A receptor antagonists. In the present analysis, three-dimensional quantitative structure–activity relationship (3D-QSAR) studies were performed on a series of pyrimidines, using comparative molecular field analysis (CoMFA). The best prediction was obtained with a CoMFA standard model (q² = 0.475, r² = 0.977) and a CoMFA region focusing model (q² = 0.637, r² = 0.976) combined with steric and electrostatic fields. The structural insights derived from the contour maps helped to better interpret the structure–activity relationships. Also, to understand the structure–activity correlation of A_2A receptor antagonists, we have carried out molecular docking analysis. Based on the results obtained from the present 3D-QSAR and docking studies, we have identified some key features for increasing the activity of compounds, which have been used to design new A_2A receptor antagonists. The newly designed molecules showed high activity with the obtained models.

Keywords:

• 3D-QSAR
• docking
• CoMFA
• A_2A receptor antagonists
• drug design