Thiadiazole derivatives as New Class of β-glucuronidase inhibitors

Uzma Salar; Muhammad Taha; Nor Hadiani Ismail; Khalid Mohammed Khan; Syahrul Imran; Shahnaz Perveen; Abdul Wadood; Muhammad Riaz

doi:10.1016/j.bmc.2016.03.020

Thiadiazole derivatives as New Class of β-glucuronidase inhibitors

Bioorg Med Chem. 2016 Apr 15;24(8):1909-18. doi: 10.1016/j.bmc.2016.03.020. Epub 2016 Mar 10.

Authors

Uzma Salar¹, Muhammad Taha², Nor Hadiani Ismail³, Khalid Mohammed Khan⁴, Syahrul Imran³, Shahnaz Perveen⁵, Abdul Wadood⁶, Muhammad Riaz⁶

Affiliations

¹ H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
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 Applied Science, Universiti Teknologi MARA, Shah Alam 40450, Selangor D. E., Malaysia. Electronic address: taha_hej@yahoo.com.
³ Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor D. E., Malaysia.
⁴ H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address: hassaan2@super.net.pk.
⁵ PCSIR Laboratories Complex, Karachi, Shahrah-e-Dr. Salimuzzaman Siddiqui, Karachi 75280, Pakistan.
⁶ Department of Biochemistry, Computational Medicinal Chemistry Laboratory, UCSS, Abdul Wali Khan University Mardan, Pakistan.

PMID: 26994638
DOI: 10.1016/j.bmc.2016.03.020

Abstract

Thiadiazole derivatives 1-24 were synthesized via a single step reaction and screened for in vitro β-glucuronidase inhibitory activity. All the synthetic compounds displayed good inhibitory activity in the range of IC50=2.16 ± 0.01-58.06 ± 1.60 μM as compare to standard d-saccharic acid 1,4-lactone (IC50=48.4 ± 1.25 μM). Molecular docking study was conducted in order to establish the structure-activity relationship (SAR) which demonstrated that thiadiazole as well as both aryl moieties (aryl and N-aryl) involved to exhibit the inhibitory potential. All the synthetic compounds were characterized by spectroscopic techniques (1)H, (13)C NMR, and EIMS.

Keywords: In vitro; Molecular docking; Structure–activity relationship; Synthesis; Thiadiazole; β-Glucuronidase.

Publication types

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

MeSH terms

Animals
Cattle
Dose-Response Relationship, Drug
Glucuronidase / antagonists & inhibitors*
Glucuronidase / metabolism
Glycoproteins / chemical synthesis
Glycoproteins / chemistry
Glycoproteins / pharmacology*
Liver / enzymology
Molecular Docking Simulation
Molecular Structure
Structure-Activity Relationship
Thiadiazoles / chemical synthesis
Thiadiazoles / chemistry
Thiadiazoles / pharmacology*

Substances

Glycoproteins
Thiadiazoles
beta-glucuronidase inhibitor
Glucuronidase