Synthesis, α-glucosidase inhibition and molecular docking study of coumarin based derivatives

Muhammad Taha; Syed Adnan Ali Shah; Muhammad Afifi; Syahrul Imran; Sadia Sultan; Fazal Rahim; Khalid Mohammed Khan

doi:10.1016/j.bioorg.2018.01.033

Synthesis, α-glucosidase inhibition and molecular docking study of coumarin based derivatives

Bioorg Chem. 2018 Apr:77:586-592. doi: 10.1016/j.bioorg.2018.01.033. Epub 2018 Feb 17.

Authors

Muhammad Taha¹, Syed Adnan Ali Shah², Muhammad Afifi³, Syahrul Imran⁴, Sadia Sultan³, Fazal Rahim⁵, Khalid Mohammed Khan⁶

Affiliations

¹ Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia. Electronic address: taha_hej@yahoo.com.
² Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor D. E., Malaysia; Faculty of Pharmacy, Universiti Tecknologi MARA Puncak Alam, 42300 Bandar Puncak Alam, Selangor D. E., Malaysia. Electronic address: syedadnan@salam.uitm.edu.my.
³ Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor D. E., Malaysia; Faculty of Pharmacy, Universiti Tecknologi MARA Puncak Alam, 42300 Bandar Puncak Alam, Selangor D. E., Malaysia.
⁴ Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor D. E., Malaysia; Faculty of Applied Science UiTM, 40450 Shah Alam, Selangor, Malaysia.
⁵ Department of Chemistry, Hazara University, Mansehra 21300, Pakistan.
⁶ H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.

PMID: 29477126
DOI: 10.1016/j.bioorg.2018.01.033

Abstract

We have synthesized seventeen Coumarin based derivatives (1-17), characterized by ¹HNMR, ¹³CNMR and EI-MS and evaluated for α-glucosidase inhibitory potential. Among the series, all derivatives exhibited outstanding α-glucosidase inhibition with IC₅₀ values ranging between 1.10 ± 0.01 and 36.46 ± 0.70 μM when compared with the standard inhibitor acarbose having IC₅₀ value 39.45 ± 0.10 μM. The most potent derivative among the series is derivative 3 having IC₅₀ value 1.10 ± 0.01 μM, which are many folds better than the standard acarbose. The structure activity relationship (SAR) was mainly based upon by bring about difference of substituent's on phenyl part. Molecular docking studies were carried out to understand the binding interaction of the most active compounds.

Keywords: Coumarin; Molecular docking study; SAR; Synthesis; α-Glucosidase inhibition.

Publication types

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

MeSH terms

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

Substances

Coumarins
Glycoside Hydrolase Inhibitors
coumarin
alpha-Glucosidases