Computational Investigation of Ligand Binding of Flavonoids in Cytochrome P450 Receptors

Abstract

Aim: The cytochrome P450 enzymes play a significant role in regulating cellular and physiological processes by activating endogenous compounds. They also play an essential role in the detoxification process of xenobiotics. Flavonoids belong to a class of polyphenols found in food, such as vegetables, red wine, beer, and fruits, which modulate biological functions in the body.

Methods: The inhibition of CYP1A1 and CYP1B1 using nutritional sources has been reported as a strategy for cancer prevention. This study investigated the interactions of selected flavonoids binding to the cytochrome P450 enzymes (CYP1A1 and CYP1B1) and their ADMET properties in silico. From docking studies, our findings showed flavonoids, isorhamnetin and pedalitin, to have the strongest binding energies in the crystal structures 6DWM and 6IQ5.

Results: The amino acid residues Asp 313 and Phe 224 in 6DWM interacted with all the ligands investigated, and Ala 330 in 6IQ5 interacted with all the ligands examined. The ligands did not violate any drug-likeness parameters.

Conclusion: These data suggest roles for isorhamnetin and pedalitin as potential precursors for natural product- derived therapies.

Keywords: ADMET; CYP1A1; CYP1B1.; Flavone; cytochrome P450; ligand docking.