Synthesis and molecular docking studies of potent α-glucosidase inhibitors based on biscoumarin skeleton

Khalid Mohammed Khan; Fazal Rahim; Abdul Wadood; Naveen Kosar; Muhammad Taha; Salima Lalani; Aisha Khan; Muhammad Imran Fakhri; Muhammad Junaid; Wajid Rehman; Momin Khan; Shahnaz Perveen; Muhammad Sajid; M Iqbal Choudhary

doi:10.1016/j.ejmech.2014.05.010

Synthesis and molecular docking studies of potent α-glucosidase inhibitors based on biscoumarin skeleton

Eur J Med Chem. 2014 Jun 23:81:245-52. doi: 10.1016/j.ejmech.2014.05.010. Epub 2014 May 4.

Authors

Affiliations

¹ H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address: [email protected].
² Department of Chemistry, Hazara University, Mansehra, Pakistan.
³ Computational Medicinal Chemistry Laboratory, Department of Biochemistry, Abdul Wali Khan University, Mardan, Mardan 23200, Pakistan.
⁴ Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia; Faculty of Applied Science, Universiti Tecknologi MARA, 40450 Shah Alam, Selangor D.E., Malaysia.
⁵ H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
⁶ Department of Chemistry, Abdul Wali Khan University, Mardan, Mardan 23200, Pakistan.
⁷ PCSIR Laboratories Complex, Karachi, Shahrah-e-Dr. Salimuzzaman Siddiqui, Karachi 75280, Pakistan.
⁸ Department of Biochemistry, Hazara University, Mansehra, Pakistan.

PMID: 24844449
DOI: 10.1016/j.ejmech.2014.05.010

Abstract

In our effort directed toward the discovery of new anti-diabetic agent for the treatment of diabetes, a library of biscoumarin derivative 1-18 was synthesized and evaluated for α-glucosidase inhibitory potential. All eighteen (18) compounds displayed assorted α-glucosidase activity with IC50 values 16.5-385.9 μM, if compared with the standard acarbose (IC50 = 906 ± 6.387 μM). In addition, molecular docking studies were carried out to explore the binding interactions of biscoumarin derivatives with the enzyme. This study has identified a new class of potent α-glucosidase inhibitors.

Keywords: Biscoumarin; Molecular docking; α-Glucosidase inhibition.

Publication types

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

MeSH terms

Coumarins / chemical synthesis
Coumarins / chemistry
Coumarins / pharmacology*
Crystallography, X-Ray
Dose-Response Relationship, Drug
Glycoside Hydrolase Inhibitors / chemical synthesis
Glycoside Hydrolase Inhibitors / chemistry
Glycoside Hydrolase Inhibitors / pharmacology*
Molecular Docking Simulation*
Molecular Structure
Structure-Activity Relationship
alpha-Glucosidases / metabolism*

Substances

Coumarins
Glycoside Hydrolase Inhibitors
alpha-Glucosidases