Design, Synthesis and Pharmacological Evaluation of 2-(3-BenzoyI-4-Hydroxy-1,1-Dioxido-2H-Benzo[e][1,2]thiazin-2-yI)-N-(2-Bromophenyl) Acetamide as Antidiabetic Agent

• Main Authors: Rashid F, Ahmad M, Ashfaq UA, Al-Mutairi AA, Al-Hussain SA
• Format: Article in Journal/Newspaper
• Language: English
• Published: Dove Medical Press 2022
• Subjects: diabetes; benzothiazine; enzyme kinetics; mice model; drug discovery; Therapeutics. Pharmacology; RM1-950; sami
• Online Access: https://doaj.org/article/fb2ae59fff61484abccd4a94907cc9bf

Fatima Rashid,1 Matloob Ahmad,2 Usman Ali Ashfaq,1 Aamal A Al-Mutairi,3 Sami A Al-Hussain3 1Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan; 2Department of Chemistry, Government College University, Faisalabad, Pakistan; 3Department of Chemistry, Faculty of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, 11623, Saudi ArabiaCorrespondence: Usman Ali Ashfaq, Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan, Email [e-mail] Sami A Al-Hussain, Department of Chemistry, Faculty of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, 11623, Saudi Arabia, Email [e-mail]: The present study is based on screening new and potent synthetic heterocyclic compounds as anti-diabetic drugs using various computational tools, lab experiments, and animal models.Methods: A potent synthetic compound 2-(3-benzoyl-4-hydroxy-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl)-1-(2-bromophenyl) acetamide (FA2) was checked against diabetes and screened via enzyme inhibition assays, enzyme kinetics against alpha-glucosidase and alpha-amylase. Protein–ligand interaction was analyzed via molecular docking and toxicological analysis via ADMET. Experimental animals were used to examine the compound FA2 safety, delivery, and check various biochemical tests related to diabetes like fasting glucose sugar, cholesterol, triglyceride, HbAc1, creatinine, and insulin level. Histography of liver, kidney, and pancreas was also performed.Results: Results showed that FA2 had binding energy of ‐7.02 Kcal/mol and ‐6.6 kcal/mol against α‐glucosidase (PDB ID: 2ZE0) and α‐amylase (PDB ID: 1B2Y), respectively. Moreover, in vitro enzyme inhibition assays and enzyme kinetics against α‐glucosidase and α‐amylase were performed, and FA2 showed IC50 at 5.17 ± 0.28 μM and 18.82 ± 0.89 μM concentrations against α‐glucosidase and α‐amylase, respectively. Kinetics studies showed that the FA2 compound impeded ...