title: Solution-phase microwave assisted parallel synthesis, biological evaluation and in silico docking studies of N,N'-disubstituted thioureas derived from 3-chlorobenzoic acid.
abstract: A facile and robust microwave-assisted solution phase parallel synthesis protocol was exercised for the development of a 38-member library of N,N'-disubstituted thiourea analogues (1-38) by using an identical set of conditions. The reaction time for synthesis of N,N'-disubstituted thiourea analogues was drastically reduced from a reported duration of 8-12h for conventional methods to only 1.5-2.0min. All the derivatives (1-38) were characterized by physico-analytical techniques such as elemental analysis in combination with FT-IR, (1)H, (13)C NMR and by single crystal XRD analysis have also been performed. These compounds were screened for their in vitro urease inhibition activities. Majority of compounds exhibited potent urease inhibition activities, however, the most significant activity was found for 16, with an IC50 value of 1.23±0.1μM. Furthermore, the synthesized compounds were screened for their cytotoxic potential against lungs cancer cell lines. Cell culture studies demonstrated significant toxicity of the compounds on the cell lines, and the levels of toxicity were altered in the presence of various side groups. The molecular docking studies of the most potent inhibitors were performed to identify the probable binding modes in the active site of the urease enzymes. These compounds have a great potential and significance for further investigations.
authors.affiliation: Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan.
authors.forename: Muhammad Khawar
authors.initials: MK
authors.lastname: Rauf
authors.affiliation: Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan.
authors.forename: Sumera
authors.initials: S
authors.lastname: Zaib
authors.affiliation: Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan.
authors.forename: Ammara
authors.initials: A
authors.lastname: Talib
authors.affiliation: Department of Chemistry, Faculty of Engineering, Gifu University, Yanagido, Gifu 501-1193, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ebihara
authors.affiliation: Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan. Electronic address: aminbadshah@yahoo.com.
authors.forename: Amin
authors.initials: A
authors.lastname: Badshah
authors.affiliation: Institut für Anorganische Chemie, J.W. Goethe-Universität Frankfurt, Max-von-Laue-Str. 7, 60438 Frankfurt/Main, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Bolte
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: D066241:Carbon-13 Magnetic Resonance Spectroscopy; D002460:Cell Line; D002723:Chlorobenzoates / Q000737:chemistry*; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008872:Microwaves; D062105:Molecular Docking Simulation; D066244:Proton Magnetic Resonance Spectroscopy; D017550:Spectroscopy, Fourier Transform Infrared; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D014510:Urease / Q000037:antagonists & inhibitors / Q000737:chemistry
chemical_list: D002723:Chlorobenzoates; D004791:Enzyme Inhibitors; C036427:3-chlorobenzoic acid; D014510:Urease; D013890:Thiourea
keywords: Cytotoxicity; Microwave assisted parallel synthesis; N,N′-Disubstituted thioureas; Single crystal analysis; Urease inhibition