Ligand-based CoMFA and CoMSIA studies on chromone derivatives as radical scavengers

Abstract

The antioxidant activity for a series of chromone compounds, evaluated by DPPH free radical scavenging assay, were subjected to 3D-QSAR studies using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). All 48 chromone derivatives were geometry optimized by AM1 and HF/6-31G*calculations. The CoMFA and CoMSIA results were compared between different alignment strategies. The best CoMFA model obtained from HF/6-31G*optimization with field fit alignment gave cross-validated r2(q2) = 0.821, noncross-validated r2= 0.987, S =0.095, and F= 388.255. The best CoMSIA model derived from AM1 optimized structures and superimposition alignment gave q2= 0.876, noncross-validated r2=0.976, S = 0.129, and F=208.073, including electrostatic, hydrophobic, hydrogen bond donor and acceptor fields. The contour maps provide the fruitful structure-radical scavenging activity relationships which are useful for designing new compounds with higher activity. © 2013 Elsevier Inc. All rights reserved.