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.

[1]  N. Gençer,et al.  In vitro effect of novel β-lactam compounds on xanthine oxidase enzyme activity , 2012, Artificial cells, blood substitutes, and immobilization biotechnology.

[2]  N. Gençer,et al.  Purification and characterization of prophenoloxidase from Galleria mellonella L. , 2012, Artificial cells, blood substitutes, and immobilization biotechnology.

[3]  N. Gençer,et al.  Effects of some metals on paraoxonase activity from shark Scyliorhinus canicula , 2012, Journal of enzyme inhibition and medicinal chemistry.

[4]  A. A. Alekseev,et al.  The phenylthiourea is a competitive inhibitor of the enzymatic oxidation of DOPA by phenoloxidase , 2012, Journal of enzyme inhibition and medicinal chemistry.

[5]  F. Köçkar,et al.  Evaluation of in vitro effects of some analgesic drugs on erythrocyte and recombinant carbonic anhydrase I and II , 2012, Journal of enzyme inhibition and medicinal chemistry.

[6]  N. Gençer,et al.  In vitro inhibition of polyphenol oxidase by some new diarylureas , 2012, Journal of enzyme inhibition and medicinal chemistry.

[7]  F. Sonmez,et al.  Evaluation of new chalcone derivatives as polyphenol oxidase inhibitors. , 2011, Bioorganic & medicinal chemistry letters.

[8]  A. Saboury,et al.  Dual effects of aliphatic carboxylic acids on cresolase and catecholase reactions of mushroom tyrosinase , 2009, Journal of enzyme inhibition and medicinal chemistry.

[9]  R. Cao,et al.  Synthesis and evaluation of 5-benzylidene(thio)barbiturate-beta-D-glycosides as mushroom tyrosinase inhibitors. , 2009, Bioorganic & medicinal chemistry letters.

[10]  Pengcheng Lv,et al.  Urea derivatives as anticancer agents. , 2009, Anti-cancer agents in medicinal chemistry.

[11]  T. Aydemir,et al.  Purification and Characterization of Glutathione-S-Transferase from Chicken Erythrocyte , 2009, Artificial cells, blood substitutes, and immobilization biotechnology.

[12]  Armando Santoro,et al.  Sorafenib: a review of its use in advanced hepatocellular carcinoma. , 2009, Drugs.

[13]  Fuwei Li,et al.  A Novel and Efficient (NHC)CuI (NHC = N-Heterocyclic carbene) Catalyst for the Oxidative Carbonylation of Amino Compounds. , 2007 .

[14]  Fuwei Li,et al.  A novel and efficient (NHC)CuI (NHC = N-heterocyclic carbene) catalyst for the oxidative carbonylation of amino compounds , 2007 .

[15]  A. Saboury,et al.  The inhibitory effect of some new synthesized xanthates on mushroom tyrosinase activities , 2007, Journal of enzyme inhibition and medicinal chemistry.

[16]  Yasunari Fujiwara,et al.  KRN951, a highly potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, has antitumor activities and affects functional vascular properties. , 2006, Cancer research.

[17]  R. Gacche,et al.  Coumarin Schiff-bases: As Antioxidant and Possibly Anti-inflammatory Agents , 2006, Journal of enzyme inhibition and medicinal chemistry.

[18]  I. Gallou,et al.  Practical synthesis of unsymmetrical ureas from isopropenyl carbamates. , 2005, The Journal of organic chemistry.

[19]  M. Oktay,et al.  Purification and characterization of polyphenol oxidase from nettle (Urtica dioica L.) and inhibitory effects of some chemicals on enzyme activity , 2005, Journal of enzyme inhibition and medicinal chemistry.

[20]  A. Saboury,et al.  The inhibition effect of some n-alkyl dithiocarbamates on mushroom tyrosinase , 2005, Journal of enzyme inhibition and medicinal chemistry.

[21]  S. Sinan,et al.  Purification of mulberry (Morus alba L.) polyphenol oxidase by affinity chromatography and investigation of its kinetic and electrophoretic properties , 2004 .

[22]  B. Gabriele,et al.  Efficient Synthesis of Ureas by Direct Palladium‐Catalyzed Oxidative Carbonylation of Amines. , 2004 .

[23]  J. Dumas,et al.  Recent developments in the discovery of protein kinase inhibitors from the urea class. , 2004, Current opinion in drug discovery & development.

[24]  B. Gabriele,et al.  Efficient synthesis of ureas by direct palladium-catalyzed oxidative carbonylation of amines. , 2004, The Journal of organic chemistry.

[25]  L. Tarhan,et al.  Dismutation Properties of Purified and GDA Modified CuZnSOD from Chicken Heart , 2004, Artificial cells, blood substitutes, and immobilization biotechnology.

[26]  M. Feroci,et al.  Selective and environmentally friendly methodologies based on the use of electrochemistry for fine chemical preparation: an efficient synthesis of N,N'-disubstituted ureas. , 2003, The Journal of organic chemistry.

[27]  A. Liavoga,et al.  Activation of polyphenol oxidase in extracts of bran from several wheat (Triticum aestivum) cultivars using organic solvents, detergents, and chaotropes. , 2002, Journal of agricultural and food chemistry.

[28]  M. Friedman.  Food browning and its prevention: an overview , 1996 .

[29]  R. Varón,et al.  A continuous spectrophotometric method for determining the monophenolase and diphenolase activities of apple polyphenol oxidase. , 1995, Analytical biochemistry.

[30]  P. Wesche-Ebeling,et al.  Strawberry Polyphenoloxidase: Extraction and Partial Characterization , 1990 .

[31]  L. Sayavedra-Soto,et al.  Inhibition of Polyphenoloxidase by Sulfite , 1986 .

[32]  L. Vámos-Vigyázó,et al.  Polyphenol oxidases and peroxidases in fruits and vegetables , 1981 .

[33]  S. Schwimmer.  Source book of food enzymology. , 1981 .

[34]  P. Markakis,et al.  The Mechanism of Sulfite Inhibition of Browning Caused by Polyphenol Oxidase , 1965 .