title: 5-Bromo-2-aryl benzimidazole derivatives as non-cytotoxic potential dual inhibitors of α-glucosidase and urease enzymes.
abstract: On the basis of previous report on promising α-glucosidase inhibitory activity of 5-bromo-2-aryl benzimidazole derivatives, these derivatives were further screened for urease inhibitory and cytotoxicity activity in order to get more potent and non-cytotoxic potential dual inhibitor for the patients suffering from diabetes as well as peptic ulcer. In this study, all compounds showed varying degree of potency in the range of (IC50=8.15±0.03-354.67±0.19μM) as compared to standard thiourea (IC50=21.25±0.15μM). It is worth mentioning that derivatives 7 (IC50=12.07±0.05μM), 8 (IC50=10.57±0.12μM), 11 (IC50=13.76±0.02μM), 14 (IC50=15.70±0.12μM) and 22 (IC50=8.15±0.03μM) were found to be more potent inhibitors than standard. All compounds were also evaluated for cytotoxicity towards 3T3 mouse fibroblast cell line and found to be completely non-toxic. Previously benzimidazole 1-25 were also showed α-glucosidase inhibitory potential. In silico studies were performed on the lead molecules i.e.2, 7, 8, 11, 14, and 22, in order to rationalize the binding interaction of compounds with the active site of urease enzyme.
authors.affiliation: Jinnah University for Women, 5-C, Nazimabad, Karachi 74600, Pakistan.
authors.forename: Tanzila
authors.initials: T
authors.lastname: Arshad
authors.affiliation: 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.
authors.forename: Khalid Mohammed
authors.initials: KM
authors.lastname: Khan
authors.affiliation: Jinnah University for Women, 5-C, Nazimabad, Karachi 74600, Pakistan.
authors.forename: Najma
authors.initials: N
authors.lastname: Rasool
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; Deparment of Chemistry, Karakoram International University, Gilgit, Pakistan.
authors.forename: Shafqat
authors.initials: S
authors.lastname: Hussain
authors.affiliation: Department of Biochemistry and Biotechnology, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
authors.forename: Humna
authors.initials: H
authors.lastname: Asghar
authors.affiliation: Department of Biochemistry and Biotechnology, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Ashraf
authors.affiliation: Department of Biochemistry, Shankar Campus, Abdul Wali Khan University, Mardan, Khyber Pukhtoonkhwa, Pakistan.
authors.forename: Abdul
authors.initials: A
authors.lastname: Wadood
authors.affiliation: Department of Biochemistry, Shankar Campus, Abdul Wali Khan University, Mardan, Khyber Pukhtoonkhwa, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Riaz
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: 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.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Taha
authors.affiliation: 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.
authors.forename: Nor Hadiani
authors.initials: NH
authors.lastname: Ismail
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005347:Fibroblasts; D051379:Mice; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014510:Urease / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000520:alpha-Glucosidases / Q000378:metabolism*
chemical_list: D001562:Benzimidazoles; D004791:Enzyme Inhibitors; C031000:benzimidazole; D000520:alpha-Glucosidases; D014510:Urease
keywords: Benzimidazole; Cytotoxicity; Dual inhibitor; In silico; In vitro; Structure–activity relationship; Thiourea; Urease; α-glucosidase