title: Synthesis, biological evaluation and molecular docking of N-phenyl thiosemicarbazones as urease inhibitors.
abstract: Urease is an important enzyme which breaks urea into ammonia and carbon dioxide during metabolic processes. However, an elevated activity of urease causes various complications of clinical importance. The inhibition of urease activity with small molecules as inhibitors is an effective strategy for therapeutic intervention. Herein, we have synthesized a series of 19 benzofurane linked N-phenyl semithiocarbazones (3a-3s). All the compounds were screened for enzyme inhibitor activity against Jack bean urease. The synthesized N-phenyl thiosemicarbazones had varying activity levels with IC50 values between 0.077 ± 0.001 and 24.04 ± 0.14 μM compared to standard inhibitor, thiourea (IC50 = 21 ± 0.11 μM). The activities of these compounds may be due to their close resemblance of thiourea. A docking study with Jack bean urease (PDB ID: 4H9M) revealed possible binding modes of N-phenyl thiosemicarbazones.
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address: abdul.hameed@iccs.edu.
authors.forename: Abdul
authors.initials: A
authors.lastname: Hameed
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
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Syeda Tazeen
authors.initials: ST
authors.lastname: Zehra
authors.affiliation: Institute of Chemical Sciences, Bahauddin Zakariya University, Multan, Pakistan.
authors.forename: Ramasa
authors.initials: R
authors.lastname: Ahmed
authors.affiliation: Institute of Chemical Sciences, Bahauddin Zakariya University, Multan, Pakistan.
authors.forename: Zahid
authors.initials: Z
authors.lastname: Shafiq
authors.affiliation: Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan.
authors.forename: Syeda Mahwish
authors.initials: SM
authors.lastname: Bakht
authors.affiliation: Institute of Chemical Sciences, Bahauddin Zakariya University, Multan, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Yaqub
authors.affiliation: Institute of Chemical Sciences, Bahauddin Zakariya University, Multan, Pakistan.
authors.forename: Mazhar
authors.initials: M
authors.lastname: Hussain
authors.affiliation: Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan.
authors.forename: Antonio
authors.initials: A
authors.lastname: de la Vega de León
authors.affiliation: Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität, Dahlmannstr. 2, D-53113 Bonn, Germany; Pharmaceutical Institute, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Furtmann
authors.affiliation: Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität, Dahlmannstr. 2, D-53113 Bonn, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bajorath
authors.affiliation: Department of Physics, University of Sargodha, Sargodha, Pakistan.
authors.forename: Hazoor Ahmad
authors.initials: HA
authors.lastname: Shad
authors.affiliation: Department of Physics, University of Sargodha, Sargodha, Pakistan.
authors.forename: Muhammad Nawaz
authors.initials: MN
authors.lastname: Tahir
authors.affiliation: Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan. Electronic address: drjamshed@ciit.net.pk.
authors.forename: Jamshed
authors.initials: J
authors.lastname: Iqbal
mesh_terms: D001665:Binding Sites; D032449:Canavalia / Q000201:enzymology; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D013882:Thiosemicarbazones / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D014510:Urease / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D013882:Thiosemicarbazones; D014510:Urease
keywords: Benzofurane derivatives; Jack bean urease; Phenyl thiosemicarbazones; Thiosemicarbazides; Thiourea; Urease inhibitor