Identification and evaluation of natural organosulfur compounds as potential dual inhibitors of α-amylase and α-glucosidase activity: an in-silico and in-vitro approach

• Published in: Medicinal chemistry research 2021-12, Vol.30 (12), p.2184-2202
• Main Authors: Ahmad, Parvej, Alvi, Sahir Sultan, Iqbal, Johar, Khan, M. Salman
• Format: Article
• Language: English
• Subjects: Acetylcysteine; Amylases; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Crystal structure; Cysteine; Enzyme kinetics; Glucosidase; Inhibitors; Inorganic Chemistry; Medicinal Chemistry; Organosulfur compounds; Original Research; Pharmacology/Toxicology; α-Amylase; α-Glucosidase; γ-Glutamylcysteine
• ISSN: 1054-2523; 1554-8120
• DOI: 10.1007/s00044-021-02799-2

We aimed to identify and evaluate natural organosulfur compounds (OSCs) from the genus Allium as potent dual inhibitors of α-amylase and α-glucosidase via a set of molecular simulations and in-vitro analysis. We reported that all OSCs fall under the acceptable scores of Lipinski’s rules and desirable ADME parameters. In-silico screening revealed that OSCs strongly interacted with α-amylase and α-glucosidase crystal structures. Our in-vitro studies with four OSCs having best ΔG-scores demonstrated that alliin, S-allyl-L-cysteine (SAC), N-acetylcysteine (NAC), and S-ethyl-L-cysteine (SEC) exhibit a marked in-vitro inhibition of α-amylase activity, whereas, γ-glutamylcysteine (GGC), SEC, alliin, and SAC potentially inhibited the in-vitro α-glucosidase activity. Our enzyme kinetics studies depicted that the selected OSCs competitively inhibited the α-amylase and α-glucosidase activity. In conclusion, this initial in-silico and the in-vitro report demonstrates the drug-likeness and ADME indices of OSCs and identifies alliin, SAC, NAC, SEC, and GGC as potential dual inhibitors of α-amylase and α-glucosidase.