<em>In silico</em> pharmacokinetic and toxicological study of Flavone analogues

Abstract

Flavone analogs are natural compounds of the flavonoid class that have a wide range of biological activities. The present study aimed to predict, with the aid of in silico methodologies, the oral bioavailability and pharmacokinetic and toxicological analyzes for three flavone analogues (apigenin, chrysin and luteonlin). The study revealed that the analogues have good oral availability, favorable pharmacokinetic and toxicological parameters. The Virtual Screening performed to predict oral bioavailability revealed that all analogues did not violate Lipinski's Rule. The in silico pharmacokinetic study revealed that all analogues have high intestinal absorption, do not cross the blood-brain barrier, are permeable by Caco-2 cells and do not inhibit P-glycoprotein. The in silico ADME study showed that all analogues inhibit the enzymes of the cytochrome P450 complex (CYP4501A2, CYP4502C9, CYP4502C19, CYP4503A4) and not only the CYP4502D6 enzyme. The in silico Toxicology study indicated that the analogues do not show toxicity by the AMES Test and are not carcinogenic. Apigenin and chrysin have low toxicity, while luteolin has moderate toxicity.