In silico drug-likeness /ADMET prediction and molecular docking studies on key chemical constituents of Crataegus Azarolus L. for preventing cardiovascular disease

Elevated plasma LDL cholesterol levels play a crucial role in cardiovascular disease development. Squalene synthase (SQS), a regulatory enzyme in cholesterol biosynthesis, is a target for controlling hypercholesterolemia. Traditional medicine recommends Crataegus Azarolus L. for heart-related conditions, including high blood pressure, irregular heartbeat, and arteriosclerosis. Our research focuses on drug-likeness/ADMET prediction and molecular docking studies of C. azarolus constituents for cardiovascular disease prevention.

Chemical constituents of C. azarolus L. were selected based on the squalene synthase co-crystal molecule (3ASX). After energy optimization with Hyperchem, Auto Dock Vina facilitated ligand docking into the SQS active site, providing data on binding methods and compound binding energy. SwissADME and SCF Bio IITD webserver were used for in silico drug-likeness/ADME predictions.

Auto Dock Vina results and pharmacokinetic (PK) studies revealed that 2,4-Di-tert-butylphenol exhibited the highest alignment with the synthetic co-crystal molecule concerning position, binding energy, and pharmacokinetic properties among herbal compounds.

Overall, 2,4-Di-tert-butylphenol demonstrated significant affinity for squalene synthase, suggesting its potential to occupy the enzyme's active site. This compound holds promise as a viable substitute for the synthetic co-crystal molecule, pending laboratory confirmation.