title: 2-(Hetero(aryl)methylene)hydrazine-1-carbothioamides as potent urease inhibitors.
abstract: A small series of 2-(hetero(aryl)methylene) hydrazine-1-carbothioamides including two aryl derivatives was synthesized and tested for their inhibitory activity against urease. Compound (E)-2-(Furan-2-ylmethylene) hydrazine-1-carbothioamide (3f), having a furan ring, was the most potent inhibitor of urease with an IC50 value of 0.58 μM. Molecular modeling was carried out through docking the designed compounds into the urease binding site to predict whether these derivatives have analogous binding mode to the urease inhibitors. The study revealed that all of the tested compounds bind with both metal atoms at the active site of the enzyme. The aromatic ring of the compounds forms ionic interactions with the residues, Ala(440), Asp(494), Ala(636), and Met(637).
authors.affiliation: Department of Chemistry, Quaid-I-Azam University, Islamabad, 45320, Pakistan.
authors.forename: Aamer
authors.initials: A
authors.lastname: Saeed
authors.forename: Aqeel
authors.initials: A
authors.lastname: Imran
authors.forename: Pervaiz A
authors.initials: PA
authors.lastname: Channar
authors.forename: Mohammad
authors.initials: M
authors.lastname: Shahid
authors.forename: Wajahat
authors.initials: W
authors.lastname: Mahmood
authors.forename: Jamshed
authors.initials: J
authors.lastname: Iqbal
mesh_terms: D032449:Canavalia / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006834:Hydrazines / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D013854:Thioamides / Q000737:chemistry* / Q000494:pharmacology; D014510:Urease / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D006834:Hydrazines; D013854:Thioamides; C029424:hydrazine; D014510:Urease
keywords: Schiff bases; molecular modeling; thiosemicarbazones; urease inhibitors