title: Evaluation of bisindole as potent β-glucuronidase inhibitors: synthesis and in silico based studies.
abstract: Bisindole analogs 1-17 were synthesized and evaluated for their in vitro β-glucuronidase inhibitory potential. Out of seventeen compounds, the analog 1 (IC50=1.62±0.04 μM), 6 (IC50=1.86±0.05 μM), 10 (IC50=2.80±0.29 μM), 9 (IC50=3.10±0.28 μM), 14 (IC50=4.30±0.08 μM), 2 (IC50=18.40±0.09 μM), 19 (IC50=19.90±1.05 μM), 4 (IC50=20.90±0.62 μM), 7 (IC50=21.50±0.77 μM), and 3 (IC50=22.30±0.02 μM) showed superior β-glucuronidase inhibitory activity than the standard (d-saccharic acid 1,4-lactone, IC50=48.40±1.25 μM). In addition, molecular docking studies were performed to investigate the binding interactions of bisindole derivatives with the enzyme. This study has identified a new class of potent β-glucouronidase inhibitors.
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address: khalid.khan@iccs.edu.
authors.forename: Khalid Mohammed
authors.initials: KM
authors.lastname: Khan
authors.affiliation: Department of Chemistry, Hazara University, Mansehra, Pakistan.
authors.forename: Fazal
authors.initials: F
authors.lastname: Rahim
authors.affiliation: Computational Medicinal Chemistry Laboratory, Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan.
authors.forename: Abdul
authors.initials: A
authors.lastname: Wadood
authors.affiliation: Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia; Faculty of Applied Science UiTM, 40450 Shah Alam, Selangor, Malaysia.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Taha
authors.affiliation: Department of Chemistry, Abdul Wali Khan University, Mardan, Mardan 23200, Pakistan.
authors.forename: Momin
authors.initials: M
authors.lastname: Khan
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Shagufta
authors.initials: S
authors.lastname: Naureen
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Nida
authors.initials: N
authors.lastname: Ambreen
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Shafqat
authors.initials: S
authors.lastname: Hussain
authors.affiliation: PCSIR Laboratories Complex, Karachi, Shahrah-e-Dr. Salimuzzaman Siddiqui, Karachi 75280, Pakistan.
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Perveen
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Mohammad Iqbal
authors.initials: MI
authors.lastname: Choudhary
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 / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D006023:Glycoproteins; D007211:Indoles; C011473:beta-glucuronidase inhibitor; D005966:Glucuronidase
keywords: Bisindole; Molecular docking; SAR; β-Glucuronidase inhibition