title: Novel 2,5-disubtituted-1,3,4-oxadiazoles with benzimidazole backbone: a new class of β-glucuronidase inhibitors and in silico studies.
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.
authors.affiliation: 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.
authors.forename: Nik Khairunissa Nik Abdullah
authors.initials: NK
authors.lastname: Zawawi
authors.affiliation: 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: taha_hej@yahoo.com.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Taha
authors.affiliation: 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: noriz118@salam.uitm.edu.my.
authors.forename: Norizan
authors.initials: N
authors.lastname: Ahmat
authors.affiliation: Department of Biochemistry, Computational Medicinal Chemistry Laboratory, UCSS, Abdul Wali Khan University Mardan, Pakistan.
authors.forename: Abdul
authors.initials: A
authors.lastname: Wadood
authors.affiliation: 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.
authors.forename: Nor Hadiani
authors.initials: NH
authors.lastname: Ismail
authors.affiliation: Department of Chemistry, Hazara University, Mansehra 21120, Pakistan.
authors.forename: Fazal
authors.initials: F
authors.lastname: Rahim
authors.affiliation: Center for Advanced Drug Research, COMSATS Institute of Information Technology, University Road, Abbottabad 22060, KPK, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ali
authors.affiliation: Faculty of Applied Science, Universiti Teknologi MARA, 40450 Shah Alam, Selangor D. E., Malaysia.
authors.forename: Norishah
authors.initials: N
authors.lastname: Abdullah
authors.affiliation: H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Khalid Mohammed
authors.initials: KM
authors.lastname: Khan
mesh_terms: D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry; D020134:Catalytic Domain; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D005966:Glucuronidase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006801:Humans; D062105:Molecular Docking Simulation; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000737:chemistry; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D005966:Glucuronidase
keywords: Benzimidazole; In silico studies; Oxadiazole; β-Glucuronidase activity