Abstract
In the present study, we evaluate garlic, Allium sativum L., Amaryllidaceae, derived natural organosulfur compounds as effective antioxidant as well as inhibitors of human beta-hydroxy-beta-methyl-glutaryl-CoA reductase. The initial in silico screening analysis of organosulfur compounds depicted that among all the tested products, N-acetylcysteine, S-ethyl-l-cysteine, alliin, and S-allyl-l-cysteine were among the best commercially available modulators of HMG-R activity (Delta G: - 4.59, - 4.57, - 4.56, and - 4.53 kcal/mol, respectively), when compared to pravastatin (Delta G: - 4.80 kcal/mol). The above-mentioned organosulfur compounds also exhibited an intense DPPH and ABTS radical scavenging potential with the best IC50 observed in N-acetylcysteine, i.e., 7.031 +/- 0.51 mu M and 5.77 +/- 0.22 mu M, respectively, which was much better than the IC50 value of ascorbic acid (16.25 +/- 0.62 mu M and 26.73 +/- 0.53 mu M, respectively). On the other hand, N-acetylcysteine, S-ethyl-l-cysteine, and alliin exhibited significant in vitro HMG-R inhibitory activity with IC50 of 139.26 +/- 1.8 mu M, 264.66 +/- 5.8 mu M, and 292.86 +/- 6.8 mu M, respectively. Additionally, our enzyme kinetics studies revealed that N-acetylcysteine exhibits competitive inhibition against in vitro beta-hydroxy-beta-methyl-glutaryl-CoA reductase activity. Based in our in silico and in vitro studies, we concluded that among other selected organosulfur compounds, N-acetylcysteine possesses significant antioxidant potential and competitively inhibits the enzymatic activity of beta-hydroxy-beta-methyl-glutaryl-CoA.