Synthesis, in vitro evaluation and molecular docking studies of thiazole derivatives as new inhibitors of α-glucosidase

Fazal Rahim; Hayat Ullah; Muhammad Tariq Javid; Abdul Wadood; Muhammad Taha; Muhammad Ashraf; Ayesha Shaukat; Muhammad Junaid; Shafqat Hussain; Wajid Rehman; Rashad Mehmood; Muhammad Sajid; Muhammad Naseem Khan; Khalid Mohammed Khan

doi:10.1016/j.bioorg.2015.06.006

Synthesis, in vitro evaluation and molecular docking studies of thiazole derivatives as new inhibitors of α-glucosidase

Bioorg Chem. 2015 Oct:62:15-21. doi: 10.1016/j.bioorg.2015.06.006. Epub 2015 Jun 29.

Authors

Affiliations

¹ Department of Chemistry, Hazara University, Mansehra 21120, Pakistan. Electronic address: fazalstar@gmail.com.
² Department of Chemistry, Hazara University, Mansehra 21120, Pakistan.
³ Department of Biohemistry, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan.
⁴ Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA, Puncak Alam Campus, Malaysia; Faculty of Applied Science, Universiti Teknologi MARA, 40450 Shah Alam, Selangor D.E., Malaysia.
⁵ Department of Biochemistry and Biotechnology, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
⁶ H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
⁷ Department of Conservation Studies, Hazara University, Mansehra 21120, Pakistan.
⁸ Department of Biochemistry, Hazara University, Mansehra 21120, Pakistan.

PMID: 26162519
DOI: 10.1016/j.bioorg.2015.06.006

Abstract

A series of thiazole derivatives 1-21 were prepared, characterized by EI-MS and (1)H NMR and evaluated for α-glucosidase inhibitory potential. All twenty one derivatives showed good α-glucosidase inhibitory activity with IC50 value ranging between 18.23±0.03 and 424.41±0.94μM when compared with the standard acarbose (IC50, 38.25±0.12μM). Compound (8) (IC50, 18.23±0.03μM) and compound (7) (IC50=36.75±0.05μM) exhibited outstanding inhibitory potential much better than the standard acarbose (IC50, 38.25±0.12μM). All other analogs also showed good to moderate enzyme inhibition. Molecular docking studies were carried out in order to find the binding affinity of thiazole derivatives with enzyme. Studies showed these thiazole analogs as a new class of α-glucosidase inhibitors.

Keywords: Molecular docking; Synthesis; Thiazole; α-Glucosidase inhibition.

Publication types

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

MeSH terms

Acarbose / pharmacology
Glycoside Hydrolase Inhibitors / chemical synthesis*
Glycoside Hydrolase Inhibitors / pharmacology*
Hydrazines / chemical synthesis*
Hydrazines / pharmacology*
Molecular Docking Simulation*
Phenols / chemical synthesis*
Phenols / pharmacology*
Saccharomyces cerevisiae Proteins / chemistry
Thiazoles / chemical synthesis*
Thiazoles / pharmacology*
alpha-Glucosidases / chemistry
alpha-Glucosidases / drug effects*

Substances

2,6-di-t-butyl-4-((2-(4-(4-chlorophenyl)thiazole-2-yl)hydrazono)methyl)-phenol
2-(2-(4-(benzyloxy)benzylidene)hydrazinyl)-4-(4-chlorophenyl)thiazole
Glycoside Hydrolase Inhibitors
Hydrazines
Phenols
Saccharomyces cerevisiae Proteins
Thiazoles
alpha-Glucosidases
Acarbose