title: Synthesis and tyrosinase inhibitory properties of novel isoquinoline urea/thiourea derivatives.
abstract: A new series of isoquinoline urea/thiourea derivatives (1-11) were synthesized, and their inhibitory effects on tyrosinase were evaluated. Isoquinoline urea/thiourea derivatives were obtained as a result of the reaction of 5-aminoisoquinoline with isocyanates or isothiocyanates. The result showed that all the synthesized compounds inhibited the tyrosinase enzyme activity. Among the compounds synthesized, 1-(4-chlorophenyl)-3-(isoquinolin-5-yl)thiourea (3) was found to be the most active one (Ki = 119.22 μM), and the inhibition kinetics analyzed using Lineweaver-Burk double reciprocal plots revealed that compound 3 was a competitive inhibitor. We also calculated HOMO-LUMO energy levels, some selected the synthesized compounds (1, 4, 11, 3, 6, 2) using Gaussian software.
authors.affiliation: Faculty of Arts and Sciences, Department of Chemistry, Sakarya University , Sakarya , Turkey.
authors.forename: Hayriye
authors.initials: H
authors.lastname: Genç
authors.forename: Mustafa
authors.initials: M
authors.lastname: Zengin
authors.forename: Emre
authors.initials: E
authors.lastname: Yavuz
authors.forename: Nahit
authors.initials: N
authors.lastname: Gençer
authors.forename: Oktay
authors.initials: O
authors.lastname: Arslan
mesh_terms: D060326:Chemistry Techniques, Synthetic; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D008968:Molecular Conformation; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000737:chemistry; D014508:Urea / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: D004791:Enzyme Inhibitors; D007546:Isoquinolines; D014508:Urea; D014442:Monophenol Monooxygenase; D013890:Thiourea; C039109:isoquinoline
keywords: inhibition; thiourea; tyrosinase; urea