Identification of Cyclic Sulfonamides with an N- Arylacetamide Group as α-Glucosidase and α-Amylase Inhibitors: Biological Evaluation and Molecular Modeling

• Published in: Pharmaceuticals (Basel, Switzerland) Vol. 15; no. 1; p. 106
• Main Authors: Saddique, Furqan Ahmad, Ahmad, Matloob, Ashfaq, Usman Ali, Muddassar, Muhammad, Sultan, Sadia, Zaki, Magdi E A
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 17.01.2022; MDPI
• Subjects: 1,2-benzothiazine; acetamide; Arthritis; Carbohydrates; Diabetes; Enzymes; Glucose; Hydrogen bonds; Hyperglycemia; Insulin resistance; Ligands; molecular modeling; Severe acute respiratory syndrome coronavirus 2; synthesis; α-amylase; α-glucosidase; synthesis; α-glucosidase; α-amylase; 1,2-benzothiazine; molecular modeling; anti-diabetic; acetamide
• ISSN: 1424-8247; 1424-8247
• DOI: 10.3390/ph15010106

Diabetes mellitus (DM), a complicated metabolic disorder, is due to insensitivity to insulin function or reduction in insulin secretion, which results in postprandial hyperglycemia. α-Glucosidase inhibitors (AGIs) and α-amylase inhibitors (AAIs) block the function of digestive enzymes, which delays the carbohydrate hydrolysis process and ultimately helps to control the postprandial hyperglycemia. Diversified 2-(3-(3-methoxybenzoyl)-4-hydroxy-1,1-dioxido-2 -benzo[ ][1,2]thiazin-2-yl)- -arylacetamides were synthesized and evaluated for their in vitro inhibitory potential against α-glucosidase and α-amylase enzymes. The compounds with chloro, bromo and methyl substituents demonstrated good inhibition of α-glucosidase enzymes having IC values in the range of 25.88-46.25 μM, which are less than the standard drug, acarbose (IC = 58.8 μM). Similarly, some derivatives having chloro, bromo and nitro substituents were observed potent inhibitors of α-amylase enzyme, with IC values of 7.52 to 15.06 μM, lower than acarbose (IC = 17.0 μM). In addition, the most potent compound, -(4-bromophenyl)-2-(4-hydroxy-3-(3-methoxybenzoyl)-1,1-dioxido-2 -benzo[e][1,2]thiazin-2-yl)acetamide ( ), was found to be a non-competitive and competitive inhibitor of α-glucosidase and α-amylase enzymes, respectively, during kinetic studies. The molecular docking studies provided the binding modes of active compounds and the molecular dynamics simulation studies of compound in complex with α-amylase also showed that the compound is binding in a fashion similar to that predicted by molecular docking studies.