Synthesis of thiobarbituric acid derivatives: In vitro α-glucosidase inhibition and molecular docking studies

Assem Barakat; M Ali; Abdullah Mohammed Al-Majid; Sammer Yousuf; M Iqbal Choudhary; Ruqaiya Khalil; Zaheer Ul-Haq

doi:10.1016/j.bioorg.2017.09.003

Synthesis of thiobarbituric acid derivatives: In vitro α-glucosidase inhibition and molecular docking studies

Bioorg Chem. 2017 Dec:75:99-105. doi: 10.1016/j.bioorg.2017.09.003. Epub 2017 Sep 12.

Authors

Assem Barakat¹, M Ali², Abdullah Mohammed Al-Majid², Sammer Yousuf³, M Iqbal Choudhary⁴, Ruqaiya Khalil⁵, Zaheer Ul-Haq⁵

Affiliations

¹ Department of Chemistry, College of Science, King Saud University, P. O. Box 2455, Riyadh 11451, Saudi Arabia; Department of Chemistry, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia, Alexandria 21321, Egypt. Electronic address: ambarakat@ksu.edu.sa.
² Department of Chemistry, College of Science, King Saud University, P. O. Box 2455, Riyadh 11451, Saudi Arabia.
³ H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
⁴ H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan; Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75210, Pakistan.
⁵ Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75210, Pakistan.

PMID: 28926784
DOI: 10.1016/j.bioorg.2017.09.003

Abstract

Synthesis, structure, and evaluation of in vitro α-glucosidase enzyme inhibition of a new class of diethylammonium salts of aryl substituted thiobarbituric acid is described. This protocol is straight, environmentally benign and efficient, involving Aldol-Michael addition reaction in one pot fashion. The 3D chemical structures of the synthesized compounds were assigned based on spectroscopic methods and X-ray single crystal diffraction analyses. All synthesized compounds 3a-3n were evaluated for their in vitro α-glucosidase enzyme inhibitory activity, whereas acarbose was used as the standard drug (IC₅₀=840±1.73µM). All tested compounds were found to possess varying degree of α-glucosidase enzyme inhibition activity with (IC₅₀=19.46±1.84-415.8±4.0µM). Compound3i(IC₅₀=19.4±1.84µM) exhibited the highest activity. To the best of knowledge this is the first report of the in vitro α-glucosidase enzyme inhibition by the diethylamonium salts of aryl substituted thiobarbituric acid. Furthermore, molecular docking studies of selected compounds were also performed to see interactions between active compounds and binding sites.

Keywords: Anti-diabetes; Chronic hyperglycemia; Thiobarbituric acid.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites
Catalytic Domain
Crystallography, X-Ray
Glycoside Hydrolase Inhibitors / chemical synthesis*
Glycoside Hydrolase Inhibitors / chemistry
Glycoside Hydrolase Inhibitors / metabolism
Inhibitory Concentration 50
Molecular Conformation
Molecular Docking Simulation
Thiobarbiturates / chemical synthesis
Thiobarbiturates / chemistry*
Thiobarbiturates / metabolism
alpha-Glucosidases / chemistry*
alpha-Glucosidases / metabolism

Substances

Glycoside Hydrolase Inhibitors
Thiobarbiturates
alpha-Glucosidases
thiobarbituric acid