Determination of the Inhibitory and Pharmacokinetic Properties of Helipyrone, Norhelipyrone, Italipyrone, Bisnorhelipyrone, and Plicatipyrone by in Silico Methods

Abstract

Helichrysum stoechas (L.), commonly known as the eternal flower, has long been used in traditional medicine for the treatment of many diseases. Previous phytochemical studies have reported that H. stoechas contains a variety of secondary metabolites, including the pyrones helipyrone, norhelipyrone, bisnorhelipyrone, plicatipyrone and italipyrone, which have been isolated from the plant. In this study, the inhibitory potential of these compounds against monoamine oxidase A (MAO-A), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tyrosinase, cyclooxygenase-2 (COX-2), dipeptidyl peptidase-4 (DPP4), angiotensin-converting enzyme (ACE), and stable 5-lipoxygenase (stable-5-LOX) was investigated using in silico approaches, including molecular docking, molecular dynamics (MD) simulations, MM/PBSA analyses, and density functional theory (DFT) calculations. In addition, the pharmacokinetic and toxicity profiles of the compounds were evaluated using ADME/T and PASS prediction tools. The molecular docking results indicated that italipyrone and plicatipyrone exhibited relatively strong binding affinities toward several target enzymes. The MD simulations and MM/PBSA analyses revealed that the ACE-N-domain-plicatipyrone and stable-5-LOX-italipyrone complexes showed binding free energies of -42.79 and -26.32 kcal/mol, respectively. The DFT results showed favorable electronic stability characteristics for the compounds studied, while ADME/T estimates showed relatively high blood-brain barrier permeability for italipyrone and plicatipyrone, and no toxicity was predicted for the tested molecules. Overall, the findings suggest that these compounds may be promising candidates for further experimental evaluation; however, additional in vitro and in vivo studies are needed to confirm their biological activities and pharmacological potential.