title: New saccharin derivatives as tyrosinase inhibitors.
abstract: A newly series of 6-(phenylurenyl/thiourenyl) saccharin (6a-y) derivatives were synthesized and their inhibitory effects on the diphenolase activity of banana tyrosinase were evaluated. A 70-fold purification of the enzyme with 6.85% yield was achieved by using a Sepharose 4B-l-tyrosine-p-amino benzoic acid affinity column. The result showed that all the synthesized compounds inhibited the tyrosinase enzyme activity. Among the compounds synthesized, 6-(3-iodophenylthiourenyl) saccharin (6s) was found to be most active one (K(i)=3.95 μM) and the inhibition kinetics analyzed by Lineweaver-Burk double reciprocal plots revealed that compound 6s was a competitive inhibitor. Structure-activity relationships study showed that generally, most of the 6-(phenylthiourenyl) saccharin derivatives (6m-y) exhibited higher inhibitory activity than 6-(phenylurenyl) saccharin derivatives (6a-l). An electron-withdrawing group at 3-position of phenylurenyl-ring increased in activity and the halogen series at 3-position of phenylthiourenyl-ring showed a qualitative relationship for higher inhibitory activity with increasing size and polarizability. We also calculated HOMO-LUMO energy levels and dipole moments of some selected the synthesized compounds (6a, 6h, 6m and 6s) using Gaussian software.
authors.affiliation: Department of Chemistry, Faculty of Art and Sciences, Balikesir University, Balikesir 10145, Turkey. ngencer@balikesir.edu.tr
authors.forename: Nahit
authors.initials: N
authors.lastname: Gençer
authors.forename: Dudu
authors.initials: D
authors.lastname: Demir
authors.forename: Fatih
authors.initials: F
authors.lastname: Sonmez
authors.forename: Mustafa
authors.initials: M
authors.lastname: Kucukislamoglu
mesh_terms: D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D007700:Kinetics; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D028521:Musa / Q000201:enzymology; D011789:Quantum Theory; D012439:Saccharin / Q000138:chemical synthesis / Q000737:chemistry*; D012984:Software; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D014442:Monophenol Monooxygenase; D012439:Saccharin