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

Pharmaceuticals

Usman Ali Ashfaq¹  Muhammad Muddassar²  Magdi E. A. Zaki³  Matloob Ahmad⁴  Furqan Ahmad Saddique⁴  Sadia Sultan⁵ 

[1]Department of Bioinformatics and Biotechnology, Government College University, Faisalabad 38000, Pakistan

[2]Department of Biosciences, COMSATS University Islamabad, Park Road, Islamabad 45500, Pakistan

[3]Department of Chemistry, Faculty of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia

[4]Department of Chemistry, Government College University, Faisalabad 38000, Pakistan

[5]Faculty of Pharmacy, Puncak Alam Campus, Universiti Teknologi MARA, Bandar Puncak Alam 42300, Selangor Darul Ehsan, Malaysia

关键词: 1,2-benzothiazine;    acetamide;    synthesis;    α-glucosidase;    α-amylase;    molecular modeling;   

DOI  :  10.3390/ph15010106

来源: DOAJ

【 摘 要 】

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-2H-benzo[e][1,2]thiazin-2-yl)-N-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 IC₅₀ values in the range of 25.88–46.25 μM, which are less than the standard drug, acarbose (IC₅₀ = 58.8 μM). Similarly, some derivatives having chloro, bromo and nitro substituents were observed potent inhibitors of α-amylase enzyme, with IC₅₀ values of 7.52 to 15.06 μM, lower than acarbose (IC₅₀ = 17.0 μM). In addition, the most potent compound, N-(4-bromophenyl)-2-(4-hydroxy-3-(3-methoxybenzoyl)-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl)acetamide (12i), 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 12i in complex with α-amylase also showed that the compound is binding in a fashion similar to that predicted by molecular docking studies.

【 授权许可】

Unknown