Pharmacophore modeling and 3D quantitative structure-activity relationship analysis of febrifugine analogues as potent antimalarial agent

Abstract

Febrifugine and its derivatives are effective against Plasmodium falciparum. Using PHASE algorithm, a five-point pharmacophore model with two hydrogen bond acceptor (A), one positively ionizable (P) and two aromatic rings (R), was developed to derive a predictive ligand-based statistically significant 3D-quantitative structure-activity relationship (QSAR) model (r 2 = 0.972, SD = 0.3, F = 173.4, Q 2 = 0.712, RMSE = 0.3, Person-R = 0.94, and r 2 pred = 0.8) to explicate the structural attributes crucial for antimalarial activity. The developed pharmacophore model and 3D QSAR model can be a substantial tool for virtual screening and related antimalarial drug discovery research.

Keywords

• Antimalarial
• febrifugine
• pharmacophore
• PHASE
• 3D QSAR