title: Synthesis, β-glucuronidase inhibition and molecular docking studies of hybrid bisindole-thiosemicarbazides analogs.
abstract: Hybrid bisindole-thiosemicarbazides analogs (1-18) were synthesized and screened for β-glucuronidase activity. All compounds showed varied degree of β-glucuronidase inhibitory potential when compared with standard d-saccharic acid 1,4-lactone (IC50=48.4±1.25μM). Compounds 4, 7, 9, 6, 5, 12, 17 and 18 showed exceptional β-glucuronidase inhibition with IC50 values ranging from 0.1 to 5.7μM. Compounds 1, 3, 8, 16, 13, 2 and 14 also showed better activities than standard with IC50 values ranging from 7.12 to 15.0μM. The remaining compounds 10, 11, and 15 showed good inhibitory potential with IC50 values 33.2±0.75, 21.4±0.30 and 28.12±0.25μM respectively. Molecular docking studies were carried out to confirm the binding interaction of the compounds.
authors.affiliation: Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA, Puncak Alam 42300, Malaysia; Faculty of Applied Science, Universiti Teknologi MARA, Shah Alam 40450, 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 42300, Malaysia; Faculty of Applied Science, Universiti Teknologi MARA, Shah Alam 40450, Selangor D.E., Malaysia.
authors.forename: Nor Hadiani
authors.initials: NH
authors.lastname: Ismail
authors.affiliation: Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA, Puncak Alam 42300, Malaysia; Faculty of Applied Science, Universiti Teknologi MARA, Shah Alam 40450, Selangor D.E., Malaysia.
authors.forename: Syahrul
authors.initials: S
authors.lastname: Imran
authors.affiliation: Department of Chemistry, Hazara University, Mansehra-21300, Khyber Pakhtunkhwa, Pakistan.
authors.forename: Fazal
authors.initials: F
authors.lastname: Rahim
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: Department of Biochemistry, Computational Medicinal Chemistry Laboratory, UCSS, Abdul Wali Khan University Mardan, Pakistan.
authors.forename: Huma
authors.initials: H
authors.lastname: Khan
authors.affiliation: Department of Chemistry, Hazara University, Mansehra-21300, Khyber Pakhtunkhwa, Pakistan.
authors.forename: Hayat
authors.initials: H
authors.lastname: Ullah
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Uzma
authors.initials: U
authors.lastname: Salar
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: D004305:Dose-Response Relationship, Drug; D005966:Glucuronidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006023:Glycoproteins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D012663:Semicarbazides / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D006023:Glycoproteins; D007211:Indoles; D012663:Semicarbazides; C011473:beta-glucuronidase inhibitor; C005151:thiosemicarbazide; D005966:Glucuronidase
keywords: Bisindole; Docking studies; Synthesis; β-glucuronidase