Novel 2,5-disubtituted-1,3,4-oxadiazoles with benzimidazole backbone: a new class of β-glucuronidase inhibitors and in silico studies

Zawawi NK 1 , Taha M 2 , Ahmat N 3 , Wadood A 4 , Ismail NH 1 , Rahim F 5 Show all authors , Ali M 6 , Abdullah N 7 , Khan KM 8

Affiliations 

  • 1 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
  • 2 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. Electronic address: [email protected]
  • 3 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. Electronic address: [email protected]
  • 4 Department of Biochemistry, Computational Medicinal Chemistry Laboratory, UCSS, Abdul Wali Khan University Mardan, Pakistan
  • 5 Department of Chemistry, Hazara University, Mansehra 21120, Pakistan
  • 6 Center for Advanced Drug Research, COMSATS Institute of Information Technology, University Road, Abbottabad 22060, KPK, Pakistan
  • 7 Faculty of Applied Science, Universiti Teknologi MARA, 40450 Shah Alam, Selangor D. E., Malaysia
  • 8 H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
Bioorg Med Chem, 2015 Jul 1;23(13):3119-25.
PMID: 26001340 DOI: 10.1016/j.bmc.2015.04.081

Abstract

A library of novel 2,5-disubtituted-1,3,4-oxadiazoles with benzimidazole backbone (3a-3r) was synthesized and evaluated for their potential as β-glucuronidase inhibitors. Several compounds such as 3a-3d, 3e-3j, 3l-3o, 3q and 3r showed excellent inhibitory potentials much better than the standard (IC50=48.4±1.25μM: d-saccharic acid 1,4-lactone). All the synthesized compounds were characterized satisfactorily by using different spectroscopic methods. We further evaluated the interaction of the active compounds and the enzyme active site with the help of docking studies.

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