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Biologia

pp 1–8 | Cite as

Alpha-glucosidase activity of novel pyrazolobenzothiazine 5,5-dioxide derivatives for the treatment of diabetes mellitus. Invitro combined with molecular docking approach

  • Saman Taj
  • Usman Ali AshfaqEmail author
  • Sana Aslam
  • Matloob AhmadEmail author
  • Sajjad Haider Bhatti
Original Article
  • 6 Downloads

Abstract

Diabetes mellitus is a metabolic disease caused due to the improper secretion of insulin which leads to hyperglycaemia. According to the International Diabetes Federation (IDF), 371 million people are affected by diabetes worldwide, while 7 million people are suffering from this disease in Pakistan. Pyrazolobenzothiazine 5,5-dioxide derivatives have anti-bacterial, anti-inflammatory, antioxidant activity and have the potential to treat diabetes and other diseases. This study was designed to perform in-silico and in-vitro analysis of pyrazolobenzothiazine 5,5-dioxide derivatives against α- glucosidase for the treatment of diabetes mellitus. For this purpose, pyrazolobenzothiazine 5,5-dioxide derivatives were synthesized in the laboratory. Molecular docking analysis of pyrazolobenzothiazine 5,5-dioxide derivatives against α- glucosidase was achieved through Molecular Operating Environment (MOE) and ranked them based on binding affinity. Compounds with strong binding interaction were selected for invitro anti-diabetic analysis by enzyme inhibition assay against α- glucosidase using p-nitrophenyl-α--D-glucopyranoside (PNPG) as a substrate. Furthermore, the dose-response analysis was performed via Microdilution method. Compounds having strong bonding interactions with the active site and high scores were selected for in-vitro analysis. Compounds 1a, 1f, 1 g, 1 h showed strong bonding interaction with the active site of α- glucosidase and have docking score − 11.303, −10.189, −10.360, −10.160 respectively. Compound 1e, 1f, 1 g and 1 h showed IC50 at the concentration of 4.7 μM, 8.8 μM, 12.2 μM and 11.2 μM respectively in ezyme inhibition assay. The outcome of this study proved helpful to determine new antidiabetic agents to minimize diabetes complication.

Keywords

Diabetes mellitus α- glucosidase Enzyme inhibition assay Molecular docking 

Abbreviations

MOE

Molecular Operating Environment

PNPG

p-nitrophenyl-α--D-glucopyranoside

Notes

Compliance with ethical standards

Conflict of interest

The authors confirm that this article content has no financial and other conflicts of interest. All authors have read and approved the contents of the research paper.

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Copyright information

© Institute of Molecular Biology, Slovak Academy of Sciences 2019

Authors and Affiliations

  1. 1.Department of Bioinformatics and BiotechnologyGovernment College University FaisalabadFaisalabadPakistan
  2. 2.Department of ChemistryGovernment College Women University FaisalabadFaisalabadPakistan
  3. 3.Department of ChemistryGovernment College University FaisalabadFaisalabadPakistan
  4. 4.Department of StatisticsGovernment College University FaisalabadFaisalabadPakistan

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