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Synthesis of Thiosemicarbazones as Substrates for Xanthine Oxidase Enzyme Activity
Corresponding Author(s) : S. Beyaztas
Asian Journal of Chemistry,
Vol. 26 No. 21 (2014): Vol 26 Issue 21
Abstract
Thiosemicarbazones were synthesized from 7-arylbicyclo[3.2.0]hept-2-en-6-ones (1a-d) and thiosemicarbazide. The compounds were purified on a silica gel column chromatography. The thiosemicarbazone compounds were tested in vitro effect on xanthine oxidase (XO) purified from bovine milk. These compounds exhibited activator effects on xanthine oxidase enzyme activity at low concentration. We examined KM and Vmax values for thiosemicarbazone derivatives at different pH values. The derivatives showed better values of KM, Vmax and Vmax/KM than xanthine. Particularly, (Z)-1-((1R,5S,E)-7-(4-methylbenzylidene)bicyclo[3.2.0]hept-2-en-6-ylidene) thiosemicarbazide (4Mtc) was the most suitable substrate, due to the lowest KM and the highest Vmax/KM values. KM and Vmax/KM values were 1 ×10-4 M and 1.11 × 106 min-1, respectively. We proposed here a novel substrate for xanthine oxidase which can be used to assess the activity of this enzyme.
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References
J.L. McManaman, M.C. Neville and R.M. Wright, Arch. Biochem. Biophys., 371, 308 (1999).
V. Massey, H. Komai, G. Palmer and G.B. Elion, J. Biol. Chem., 245, 2837 (1970).
R. Harrison, Free Radic. Biol. Med., 33, 774 (2002).
R. Harrison, Int. Dairy J., 16, 546 (2006).
N. Silanikove, F. Shapiro and G. Leitner, Biochem. Biophys. Res.Commun., 363, 561 (2007).
C. Galbusera, P. Orth, D. Fedida and T. Spector, Biochem. Pharmacol., 71, 1747 (2006).
J.M. Pauff and R. Hille, J. Nat. Prod., 72, 725 (2009).
R. Hille, Eur. J. Inorg. Chem., 2006, 1913 (2006).
K.R. Sathisha, S.A. Khanum, J.N.N.S. Chandra, F. Ayisha, S. Balaji, G.K. Marathe, S. Gopal and K.S. Rangappa, Bioorg. Med. Chem., 19, 211 (2011).
M.G. Bonini, S. Miyamoto, P.D. Mascio and O. Augusto, J. Chem. Biol., 279, 51836 (2004).
E. Kulikowska, B. Kierdaszuk and D. Shugar, Acta Biochim. Pol., 51, 493 (2004).
K. Okamoto, Y. Kawaguchi, B.T. Eger, E.F. Pai and T. Nishino, J. Am. Chem. Soc., 132, 17080 (2010).
T. Nishino, K. Okamoto, B.T. Eger, E.F. Pai and T. Nishino, FEBS J., 275, 3278 (2008).
Z.L. You, D.H. Shi, C. Xu, Q. Zhang and H.L. Zhu, Eur. J. Med. Chem., 43, 862 (2008).
J.H. Kim, J.A. Odutola, J. Popham, L. Jones and S. von Laven, J. Inorg. Biochem., 84, 145 (2001).
J. George and A. Struthers, J. Therap. Clinic Risk Manage., 5, 799 (2009).
D.M. Yellon and D. Hausenloy, J. N. Engl. J. Med., 357, 1121 (2007).
C. Li and R.M. Jackson, Am. J. Physiol. Cell Physiol., 282, 227 (2002).
Pal, F. Basuli and S. Bhattacharya, J. Chem. Sci., 114, 255 (2002).
I. Kizilcikli, Y.D. Kurt, B. Akkurt, A.Y. Genel, S. Birteksöz, G. Ötük and B. Ülküseven, Folia Microbiol. (Praha), 52, 15 (2007).
M.C. Rodriguez-Arguelles, M.B. Ferrari, G.G. Fava, C. Pelizzi, G. Pelosi, R. Albertini, A. Bonati, P.P. Dall'Aglio, P. Lunghi and S. Pinelli, J. Inorg. Biochem., 66, 7 (1997).
J. Perez, A. Matesanz, A. Martinambite, P. Navarro, C. Alonso and P. Souza, J. Inorg. Biochem., 75, 255 (1999).
N. Özer, M. Müftüoglu, D. Ataman,A. Ercan and I.H. Ögüs, J. Biochem. Biophys., 39, 153 (1999).
V. Massey, P.E. Brumby and H. Komai, J. Biol. Chem., 244, 1682 (1969).
M.M. Bradford, Anal. Biochem., 72, 248 (1976).
U.K. Laemmli, Nature, 227, 680 (1970).
R. Harrison, Drug Metab. Rev., 36, 363 (2004).
M.A. Hediger, R.J. Johnson, H. Miyazaki and H. Endou, Physiology (Bethesda), 20, 125 (2005).
R. Hille, Arch. Biochem. Biophys., 433, 107 (2005).
C.R. Stevens, T.M. Millar, J.G. Clinch, J.M. Kanczler, T. Bodamyali and D.R. Blake, Lancet, 356, 829 (2000).
A. Bytyqi-Damoni, H. Genç, M. Zengin, S. Beyaztas, N. Gençer and O. Arslan, Art. Cells Blood Subst. Biotech., 40, 369 (2012).
S. Beyaztas and O. Arslan, J. Biol. Chem., 39, 195 (2011).
M. Ceylan and E. Findik, Synth. Commun., 39, 1046 (2009).
R. Hile and T. Nishino, FASEB J., 9, 995 (1995).