Computational, Experimental Structural Characterization and Molecular Docking Studies of 5,7-Dihydroxy-4-methoxyflavone against Cytochrome P450 Enzymes

Abstract

In this work, the geometry optimization and harmonic vibrational wavenumbers of kaempferide (5,7-dihydroxy-4-methoxyflavone) were computed by density functional theory (DFT) method. Theoretically computed vibrational wavenumbers were compared with experimental values and the interpretation of the vibrational spectra has been studied. Frontier molecular orbitals (FMO) and molecular electrostatic potential (MEP) analysis of the title compound have been carried out. The 1H & 13C NMR, UV visible and electronic properties of the compound were investigated theoretically and compared with the experimental values. Molecular docking study of the compound against cytochrome P450 family enzymes (CYPs 1A1, 1A2, 3A4, 2C8, 2C9 and 2D6) were also studied and the results revealed that the title compound interact with human CYP2C8 enzymes with minimum binding energy of -9.43 kcal/mol. The compound forms hydrogen bond with the residues of Thr302, Thr305, Leu361, Val362, Cys435, Gln356 and Ala297. Thus, these studies assist to understand the inhibitory mechanism of kaempferide with CYP450 enzymes and may facilitate significant clinical implications in the prevention and treatment of various therapeutic diseases.