title: Design, synthesis, molecular docking studies and in vitro screening of ethyl 4-(3-benzoylthioureido) benzoates as urease inhibitors.
abstract: Thioureas are exceptionally versatile building blocks towards the synthesis of wide variety of heterocyclic systems, which also possess extensive range of pharmacological activities. The substituted benzoic acids were converted into corresponding acid chlorides, these acid chlorides were then treated with potassium thiocyanate in acetone and then the reaction mixture was refluxed for 1-2h afford ethyl 4-(3-benzoylthioureido)benzoates thioureas in good yields. All the newly synthesized compounds were evaluated for their urease inhibitory activities and were found to be potent inhibitors of urease enzyme. Compounds 1f and 1g were identified as the most potent urease inhibitors (IC50 0.21 and 0.13 μM, respectively), and was 100-fold more potent than the standard inhibitors. Further molecular docking studies were carried out using the crystal structure of urease to find out the binding mode of the inhibitors with the enzyme.
authors.affiliation: Department of Chemistry, Quaid-I-Azam University, Islamabad, Pakistan.
authors.forename: Aamer
authors.initials: A
authors.lastname: Saeed
authors.affiliation: Department of Pharmaceutical Sciences, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan.
authors.forename: Muhammad Siraj
authors.initials: MS
authors.lastname: Khan
authors.affiliation: Department of Chemistry, University of Gujrat, Gujrat 50700, Pakistan.
authors.forename: Hummera
authors.initials: H
authors.lastname: Rafique
authors.affiliation: Fraunhofer Institute SCAI, Department of Bioinformatics, Germany.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Shahid
authors.affiliation: Department of Pharmaceutical Sciences, 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: D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D001565:Benzoates / Q000737:chemistry / Q000494:pharmacology*; D032449:Canavalia / Q000201:enzymology; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014510:Urease / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000975:Antioxidants; D001565:Benzoates; D004791:Enzyme Inhibitors; D014510:Urease
keywords: Antioxidant activity; Ethyl 4-(3-benzoylthioureido)benzoates; Molecular docking; Urease inhibition