Novel Carbonic Anhydrase Activators in the Rats Exposed to H2O2

Yıl 2016, Cilt: 44 Sayı: 4, 409 - 417, 01.11.2016

Müslüm Kuzu Ramazan Demirdağ Ahmet Özkaya Veysel Çomaklı Zafer Şahin Ugur Dardağan Kader Uzun Murat Koca

Öz

Carbonic anhydrase has an important role in attentional gating of memory storage, signal process and long term synaptic transformation beside its pH regulation, HCO- reabsorption and CO2 expiration tasks. Within the study, in vivo effects of Benzofurane-2-yl 3-phenyl-3-methylcyclobutyl ketoxime A , Benzofurane-2-yl 3-methyl-3-mesitylcyclobutyl ketone thiosemicarbazone T , 1,3-bis 2-chlorbenzoyl imidazoline-2-thione B which are synthetic products and H2O2 H on the carbonic anhydrase activity in the liver, erythrocyte, heart and kidney tissues of male Wistar rat were analyzed. For this purpose, control group, separate groups for each of the synthetic products, H2O2 group and H2O2 combination group with synthetic products were created. As a result of the obtained evidence, a decrease in carbonic anhydrase activity was observed in examined tissues exposed to H2O2, but A compound has activation effect on enzyme activity in liver, T compound has it in eryt- hrocyte and heart tissues, B compound has it in liver and erythrocytes.

Anahtar Kelimeler

activation, Carbonic anhydrase, H2O2, in vivo, thiosemicarbazone

HO Uygulanan Sıçanlarda Yeni Karbonik Anhidraz Aktivatörleri

Öz

K arbonik anhidrazın pH düzenlenmesi, HCO- geri emilimi, CO’in solunumla atılması gibi görevlerinin yanısısıra, hafıza, sinyal prosesleri, uzun dönem sinaptik transformasyon olaylarında önemli rolleri vardır. Yapılan çalışmada, sentetik ürünler olan Benzofuran-2-il 3-fenil-3-metilsiklobutil ketoksim A , Benzofuran2-il 3-metil-3-mezitilsiklobutil keton tiyosemikarbazon T , 1,3-bis 2-klorobenzoil imidazolin-2-tiyon B ve HO’in karbonik anhidraz aktivitesi üzerine erkek Wistar karaciğer, eritrosit, kalp ve böbrek dokularında etkileri incelendi. Bu amaçla, kontrol grubu, her bir sentetik ürün için bir grup, H2O2 grubu ve sentetik ürünler ile HO kombinasyon grupları oluşturuldu. Elde edilen verilerden HO uygulan grupta bütün dokularda karbonik anhidraz aktivitesinde azalma olduğu görüldü. Bununla birlikte A maddesi karaciğerde aktivasyona neden olurken T maddesi eritrosit ve kalp dokularında, B maddesi ise karaciğer ve eritrositlerde aynı etkiyi gösterdi

Anahtar Kelimeler

Aktivasyon, Karbonik Anhidraz, H2O2, In vivo, tiyosemikarbazon

Kaynakça

• 1. C.T. Supuran, A. Scozzafava, Carbonic Anhydrase Inhibitors, Curr. Med. Chem., 1 (2001), 61-97.
• 2. W.R. Chegwidden, Y. Edwards, N. Carter, The Carbonic Anhydrases-New Horizons. Molecular Bases of Inherited Disease (Scriver CR; Beaudet AL, Sly WS, Valle D, eds) 8th Ed., 2165–2204, McGraw-Hill, Inc., NewYork, 2000.
• 3. C.T. Supuran, A. Scozzafava. Carbonic anhydrase inhibitors –Part 94. 1,3,4-Thiadiazole-2-sulfonamide derivatives as antitumor agents? Eur. J. Med. Chem., 35 (2000), 867-874.
• 4. M. Koca, S. Servi, C. Kirilmis, M. Ahmedzade, C. Kazaz, B. Özbek, G. Ötük, Synthesis and antimicrobial activity of some novel derivatives of benzofuran: part 1. Synthesis and antimicrobial activity of (benzofuran2-yl)(3-phenyl-3-methylcyclobutyl) ketoxime derivatives, Eur. J. Med. Chem., 40 (2005), 1351–1358.
• 5. V. Ugale, H. Patel, B. Patel, S. Bari, Benzofuranoisatins: Search for antimicrobial agents, Arabian J. Chem., doi:10.1016/j.arabjc.2012.09.011, (2012).
• 6. C. Kirilmis, M. Ahmedzade, S. Servi, M. Koca, A. Kizirgil, C. Kazaz, Synthesis and antimicrobial activity of some novel derivatives of benzofuran: Part 2. The synthesis and antimicrobial activity ofsome novel 1-(1-benzofuran-2-yl)-2-mesitylethanone derivatives, Eur. J. Med. Chem., 43 (2008), 300-308.
• 7. R.J. Nevagi, S.N. Dighe, S.N. Dighe, Biological and medicinal significance of benzofuran, Eur. J. Med. Chem., 97 (2015), 561-581.
• 8. N. İkizoğlu, Reactions of Imidazole and Oxindole wtih Metal Compounds, Characterization of Structures of Synthesized Complexes. Master’s thesis, Kocaeli University: Kocaeli, (2012).
• 9. İ. Sarı, The investigation of the effect of component containing benzofurane and benzimidazol on the some parameters at blood of rats (Wistar). Master’s thesis, Fırat University: Elazığ, (2009).
• 10. A.E. Liberta, D.X. West, Antifungal and antitumor activity of heterocyclic thiosemicarbazones and their metal complexes: current status, Biometals, 5 (1992), 121-126.
• 11. T. Rosu, A. Gulea, A. Nicolae, R. Georgescu, Complexes of 3dn Metal Ions with Thiosemicarbazones: Synthesis and Antimicrobial Activity. Molecules, 12 (2007), 782- 796.
• 12. J.M.C. Gutteridge, Free Radicals in Diseases Processes: A Compilation of Cause and Consequence, Free Radical Res. Com., 19 (1993), 141– 158.
• 13. P. Storz, Reactive Oxygen Species in Tumor Progression, Frontiers in Bioscience, 10 (2005), 1881– 1896.
• 14. S. Öztürk Yıldırım, M. Akkurt, M. Genç, M. Şekerci, H.K. Fun, 1,3-bis(2-klorbenzoil)imidazolin-2-tiyon, Anal. Sci., 22 (2006), 171.
• 15. M.A. Ahmedov, I.M. Ahmedov, A.V. Kisin, R.R Kostikov, I.K. Sardarov, N.M. Babaev, Formation of substituted cyclobutanes in the reaction of 2-(2-methyl-2- prophenyl)-3-chloromethyloxirane witharomatic hydrocarbons, Zhr. Org. Chem., 27 (1991), 1254–1262.
• 16. M. Koca, M. Ahmedzade, A. Çukurovali, C. Kazaz, Studies on the Synthesis and Reactivity of Novel Benzofuran-2-yl-[3-Methyl-3-Phenylcyclobutyl] Methanones and their Antimicrobial Activity, Molecules, 10 (2005), 747-754.
• 17. M.M. Bradford. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein–dye binding, Anal. Biochem., 72 (1976), 248–251.
• 18. J.A. Verpoorte, S. Mehta, J.T. Edsall, Esterase activities of human carbonic anhydrases B and C. J. Biol. Chem., 242 (1967), 4221-4229.
• 19. V.S. Carratu, L. Bresolin, J.B.T.D. Rocha, F.A.A Soares, Butane-2,3-dionethiosemicarbazone: An oxime with antioxidant properties, Chem-Biol. Interact., 177 (2009), 153-160.
• 20. Y.S. Xie, D. Kumar, V.D.V. Bodduri, P.S. Tarani, B.X. Zhao, J.Y. Miao , K. Jang, D.S. Shin, Microwaveassisted parallel synthesis of benzofuran-2- carboxamide derivatives bearing anti-inflammatory, analgesic and antipyretic agents, Tetrahedron Lett., 55 (2014), 2796–2800.
• 21. P.G. Baraldi, R. Romagnoli, M.G. Pavani, Benzoyl and cinnamoyl nitrogen mustard derivatives of benzoheterocyclic analogues of the tallimustine: Synthesis and antitumour activity, Bioorgan. Med. Chem., 10 (2002), 1611-1618.
• 22. I. Hayakawa, R. Shioya, T. Agatsuma, Thienopyridine and benzofuran derivatives as potent anti-tumor agents possessing different structure-activity relationships, Bioorg. Med. Chem. Lett., 14 (2004), 3411-3414.
• 23. S. Parekh, D. Bhavsar, M. Savant, S. Thakrar, A. Bavishi, M. Parmar, H. Vala, A. Radadiya, N. Pandya, J. Serly, J. Molnár, A. Shah, Synthesis of some novel benzofuran-2-yl(4,5-dihyro-3,5-substituted diphenylpyrazol-1-yl) methanones and studies on the antiproliferative effects and reversal of multidrug resistance of human MDR1 -gene transfected Mouse lymphoma cells in vitro, Eur. J. Med. Chem, 46 (2011), 1942-1948.
• 24. J.M. Grisar, F.N. Bolkenius, M.A. Petty, 2,3-Dihydro1-benzofuran-5-ols as analogs of a-tocopherol that ınhibit in-vitro and ex-vivo lipid autoxidation and protect mice against centralnervous-system trauma, J. Med. Chem., 38 (1995), 453-458.
• 25. B. Prathima, Y.S. Rao, S.A. Reddy, Y.P. Reddy, A.V. Reddy, Copper(II) and nickel(II) complexes of benzyloxybenzaldehyde-4-phenyl-3- thiosemicarbazone: Synthesis, characterization and biological activity, Spectrochim. Acta A, 77 (2010), 248-252.
• 26. M.K. Sun, D.L. Alkon, Pharmacological Enhancement of Synaptic Efficacy, Spatial Learning, and Memory through Carbonic Anhydrase Activation in Rats, J. Pharmacol. Exp. Ther., 297 (2002), 961-967.
• 27. C.T. Supuran, Carbonic anhydrases: novel therapeutic applications for inhibitors and activators, Nat. Rev. Drug. Discov., 7 (2008), 1-14.
• 28. C.T. Supuran, M. Barboiu, C. Luca, E. Pop, M.E. Brewster, A. Dinculescu, Carbonic anhydrase activators. Part 14*. Syntheses of mono and bis pyridinium salt derivatives of 2-amino-5 (2-aminoethyl)- and 2-amino-5(3-aminopropyl)-1,3,4-thiadiazole and their interaction with isozyme II. Eur. J. Med. Chem., 31 (1996), 597-606.
• 29. E. Cherubini, Y.B. Ari, M. Gho, J.N. Bidard, M. Lazdunski, Long-term potentiation of synaptic transmission in the hippocampus induced by a bee venom peptide, Nature, 328 (1987), 70-73.
• 30. P. Panula, J. Rinne, K. Kuokkanen, K.S. Eriksson, T. Sallmen, H. Kalimo, M. Relja, Neuronal histamine deficit in Alzheimer’s disease. Neuroscience, 82 (1997), 993-997.
• 31. M-K. Sun, T.J. Nelson, D.L. Alkon, Functional switching of GABAergic synapses by ryanodine receptor activation, Proc. Natl. Acad. Sci., 97 (2000), 12300–12305.
• 32. K.J. Staley, B.L. Soldo, W.R. Proctor, Ionic mechanisms of neuronal excitation by inhibitory GABAA receptors, Science, 269 (1995), 977–981.
• 33. M-K. Sun, T.J. Nelson, H. Xu, D.L. Alkon, Calexcitin transformation of GABAergic synapses from excitation filter to amplifier, Proc Natl Acad Sci., 96 (1999), 7023–7028.
• 34. A. Quincozes-Santos, L.D. Bobermin, A. Latini, M. Wajner, D.O. Souza, C-A. Gonçalves, C. Gottfried, Resveratrol Protects C6 Astrocyte Cell Line against Hydrogen Peroxide-Induced Oxidative Stress through Heme Oxygenase 1, PloS One, 8 (2013), 1-1.
• 35. E.M. Gözükara, Biyokimya, 5. Baskı, Nobel Tıp Kitabevleri, Hadımköy-İstanbul (2011).