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

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...

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Published inPharmaceuticals (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
LanguageEnglish
Published Switzerland MDPI AG 17.01.2022
MDPI
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Summary: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.
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ISSN:1424-8247
1424-8247
DOI:10.3390/ph15010106