A molecular informatics and in-vitro approach to evaluate the HMG-CoA reductase inhibitory efficacy of monoterpenes, carvacrol and geraniol

Abstract

Currently, statins, the β-hydroxy-β-methyl-glutaryl-CoA reductase (HMG-R) inhibitors, are widely used to lower cholesterol, nevertheless, they have several side effects. Consequently, the present study is designed to unravel the cardioprotective role of selected natural monoterpenoids (carvacrol and geraniol) via in-vitro targeting and molecular informatics study of HMG-R. Computational molecular informatics study revealed that carvacrol and geraniol efficiently occupies the catalytic site of HMG-R with the binding affinity (ΔG) of −4.60, and −1.99 Kcal/mol, respectively, and molecular mechanical-generalized Born surface area (MM-GBSA) free binding energy was depicted as −17.05 and −29.48 Kcal/mol, respectively. Further, molecular dynamics simulation was carried out for 100 ns. Carvacrol and geraniol potentially and competitively inhibit the in-vitro HMG-R activity with an IC50 value of 78.23 ± 2.21 µM, and 72.91 ± 2.92 µM, respectively. Thus, both carvacrol and geraniol exhibited significant anti-hypercholesterolemic activity while the molecular simulation studies depicted that the GR complex showed better stability than the carvacrol complex.

Keywords

• Atherosclerosis
• hypercholesterolaemia
• monoterpenes
• HMG-R inhibition
• enzyme kinetics
• molecular docking