Molecular Docking & In Silico ADME Analysis of 5-O-Methyl-11-O-Acetylalkannin

Abstract

In the early phases of drug development, prediction of pharmacokinetic parameters including absorption, distribution, metabolism, and elimination (ADME), before synthesis may be helpful in the selection of candidates with less significant pharmacokinetic profiles. 5-O-methyl-11-O-acetylalkannin (MAA) is naphthoquinone isolated from the roots of Alkanna genus, Alkanna cappadocica. The aim of the present study is to predict the in silico ADME study of MAA using web tool called SwissADME. The 2D structure of the compound was drawn on Chemdraw Ultra version 8.0. The colored zone represents the optimal physicochemical region for oral bioavailability, according to the bioavailability radar, which takes into account the characteristics of flexibility, lipophilicity, saturation, size, polarity, and solubility. The pharmacokinetic properties were analyzed using the boiled egg model. The yolk-colored yellow component has a high chance of entering the brain, whereas the white portion has a high chance of being passively absorbed by the gastrointestinal tract. The study concluded that MAA did not violate the recommended ranges for Lipinski’s rule of five, rotational bond count, and Topological Polar Surface Area (TPSA). MAA also showed moderate lipophilicity and good water solubility. It did not act as a substrate for P-glycoprotein. MAA displayed a potential to inhibit CYP1A2, CYP2C19, CYP2C9 and CYP3A4. Besides that, MAA exhibited no action against CYP2D6. It exhibited a uniform and good bioavailability score of 0.55 (55%) with high gastrointestinal (GI) absorption capabilities. Additionally, the Synthetic Accessibility score of the MAA represented easy-step reactions of synthesis. MAA does not violate any of the five drug-likeness parameters including Lipinski, Muegge, Ghose, Veber, and Egan rules. As a result, MAA could be considered a promising molecule in drug discovery. Moreover, the molecular docking analysis showed the formation of a stable protein ligand complex between TNFα and the ligand molecule.