Synthesis and α-Glucosidase Inhibition Activity of 2-[3-(Benzoyl/4-bromobenzoyl)-4-hydroxy-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl]-N-arylacetamides: An In Silico and Biochemical Approach
| Autor: | Sana Aslam, Usman Ali Ashfaq, Sadia Sultan, Magdi E. A. Zaki, Muhammad Muddassar, Muzammil Hussain, Matloob Ahmad, Dae Sung Lee, Furqan Ahmad Saddique, Saman Taj |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
synthesis
medicine.medical_treatment In silico Drug Evaluation Preclinical Thiazines Pharmaceutical Science 1 2-Benzothiazines 01 natural sciences Article Analytical Chemistry Inhibitory Concentration 50 Structure-Activity Relationship QD241-441 Drug Discovery Acetamides medicine Diabetes Mellitus Monosaccharide Structure–activity relationship Humans Hypoglycemic Agents Computer Simulation Glycoside Hydrolase Inhibitors Physical and Theoretical Chemistry IC50 Acarbose chemistry.chemical_classification 010405 organic chemistry Insulin α-glucosidase inhibition Organic Chemistry molecular docking anti-diabetic 0104 chemical sciences Molecular Docking Simulation 010404 medicinal & biomolecular chemistry Enzyme chemistry Biochemistry Chemistry (miscellaneous) Docking (molecular) Molecular Medicine medicine.drug |
| Zdroj: | Molecules Volume 26 Issue 10 Molecules, Vol 26, Iss 3043, p 3043 (2021) |
| ISSN: | 1420-3049 |
| Popis: | Diabetes mellitus (DM) is a chronic disorder and has affected a large number of people worldwide. Insufficient insulin production causes an increase in blood glucose level that results in DM. To lower the blood glucose level, various drugs are employed that block the activity of the α-glucosidase enzyme, which is considered responsible for the breakdown of polysaccharides into monosaccharides leading to an increase in the intestinal blood glucose level. We have synthesized novel 2-(3-(benzoyl/4-bromobenzoyl)-4-hydroxy-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl)-N-arylacetamides and have screened them for their in silico and in vitro α-glucosidase inhibition activity. The derivatives 11c, 12a, 12d, 12e, and 12g emerged as potent inhibitors of the α-glucosidase enzyme. These compounds exhibited good docking scores and excellent binding interactions with the selected residues (Asp203, Asp542, Asp327, His600, Arg526) during in silico screening. Similarly, these compounds also showed good in vitro α-glucosidase inhibitions with IC50 values of 30.65, 18.25, 20.76, 35.14, and 24.24 μM, respectively, which were better than the standard drug, acarbose (IC50 = 58.8 μM). Furthermore, a good agreement was observed between in silico and in vitro modes of study. |
| Databáze: | OpenAIRE |
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