IN VITRO INHIBITION OF BOVINE LIVER CARBONIC ANHYDRASE II BY SOME DRUGS

Yıl 2015, Cilt: 3 Sayı: 1, 334 - 339, 01.01.2015

İmdat Aygül , Nuri Güleşçe

Öz

Karbonik anhidraz enzimi (EC: 4.2.1.1; CA) sığır karaciğerinden saflaştırılarak bazı antibiyotiklerin inhibisyon etkileri incelendi. Saflaştırma prosedürü, homojenatın hazırlanması ve Sepharoz 4B-Tirozin-Sulfanamid Kromatografisinden oluştu. Birbirini takip eden bu iki yöntem ile
enzim 65,24 kat, % 50,86 verimle ve spesifik aktivitesi 1117.24 U/mg protein olarak saflaştırıldı. Enzim üzerine bazı antibiyotik ilaçların in vitro inhibisyon etkileri belirlendi. Bu inhibitörler için IC 50 değerleri, % aktiviteye karşı inhibitor konsantrasyon [I] grafiği çizilmek suretiyle belirlendi. Siprofloksazin ve seftazidim inhibitörlerinin IC değerleri sırasıyla 1.27 ve 5.29 mM olarak tespit 50 edildi.

 

          Anahtar Kelimeler: Karbonik anhidraz(CA), Sığır, Karaciğer, İnhibitör, Antibiyotik

Anahtar Kelimeler

Karbonik anhidraz(CA), Sığır, Karaciğer, İnhibitör, Antibiyotik

Kaynakça

• Kim, J.S., Gay, C.V., Schrarer, R. Purification and properties of carbonic anhydrase from salmon erythrocytes. Comp. Biochem. Physiol. Part B. 76, 523-527, 1983.
• Ekinci, D., Cavdar, H., Durdagi, S., Talaz, O., Senturk, M., Supuran, C.T. Structureactivity relationships for the interaction of 5,10-dihydroindeno[1,2-b]indole derivatives with human and bovine
• carbonic anhydrase isoforms I, II, III, IV and VI. European Journal of Medicinal Chemistry. 49, 68-73, 2012.
• Demirdag, R., Yerlikaya, E., Senturk, M., Kufrevioglu, O.I., Supuran, C.T. Heavy metal ion inhibition studies of human, sheep and fish α-carbonic anhydrases. Journal of Enzyme Inhibition and Medicinal Chemistry. 28, 278-282, 2013.
• Supuran ,C.T., Scozzafava, A.Applications of carbonic anhydrase. Inhibitors and activators in therapy. Expert Opin. Ther. Pat. 12, 217–242, 2002.
• Supuran, C.T. Carbonic anhydrases: novel therapeutic applications for inhibitors and activators, Nat. Rev. Drug Discov. 7, 168 - 181,2008.
• Innocenti, A. Maresca, A. Scozzafava, A. Supuran, C.T. Carbonic anhydrase i n h i b i t o r s : t h i o x o l o n e v e r s u s sulfonamides for obtaining isozymeselective inhibitors? Bioorg. Med. Chem. Lett. 18, 3938-3941, 2008.
• Scozzafava, A., Supuran, C.T. Hydroxyurea Is a Carbonic Anhydrase Inhibitor. Bioorg. Med. Chem. 11, 2241-2246, 2003.
• Verpoorte, J.A. Esterase Activities of Human Carbonic Anhydrases B and C Mehta S, Edsall J.T. Biol. Chem. 242, 4221-4229, 1967.
• Ekinci, D., Karagoz, L., Ekinci, D., Senturk, M., Supuran, C.T. Carbonic anhydrase inhibitors: in vitro inhibition of α isoforms (hCA I, hCA II, bCA III, hCA IV) by flavonoid. Journal of Enzyme Inhibition and Medicinal Chemistry. 28, 283-288, 2013.
• Demirdag, R., Comakli, V., Kuzu, M., Yerlikaya, E., Senturk, M. Purification and Characterization of Carbonic Anhydrase from Ağrı Balık Leke Trout Gill (Salmo trutta labrax) and Effects of Sulfonamides on Enzyme Activity. Journal of Biochemical and Molecular Toxicology. 29, 123-128, 2015.
• Supuran, C.T. Carbonic anhydrase inhibitors, Bioorg. Med. Chem. Lett. 2010, 20 , 3467-3474.
• Şentürk, M., Ekinci, D., Göksu, S., & Supuran, C. T. Effects of dopaminergic compounds on carbonic anhydrase isozymes I, II, and VI.Journal of enzyme inhibition and medicinal chemistry, 27(3), 365-369, 2012.
• Xing, H. Qu, R. A compact genetic algorithm for the network coding based resource minimizat_on problem, Applied Intelligence, 36, 4, 809-823, 2011.
• Bayram E, Senturk M, Kufrevioglu OI, Supuran C .T. In vitro inhibition of salicylic acid derivatives on human cytosolic carbonic anhydrase isozymes I and II. Bioorg Med Chem 16, 9101-9105, 2008.
• Renzi G, Scozzafava A, Supuran CT. Carbonic anhydrase inhibitors: topical
• sulfonamide antiglaucoma agents incorporating secondary amine moieties.
• Bioorg Med Chem Lett10, 673-676, 2000.
• Coban TA, Beydemir S, Gülçin I, Ekinci D. The effect of ethanol on erythrocyte carbonic anhydrase isoenzymes activity: an in vitro and in vivo study. J Enzyme Inhib Med Chem., 23: 266-270, 2008.
• Senturk, M., Alici, H.A., Beydemir, S., Kufrevioglu, O.I . I n vitro and in vivo effects of some benzodiazepine drugs on human and rabbit erythrocyte carbonic anhydrase enzymes. Journal of Enzyme Inhibition and Medicinal Chemistry, 27, 680-684, 2012
• Guney, M., Cavdar, H., Senturk, M., Ekinci, D. Synthesis and carbonic
• anhydrase inhibitory properties of novel uracil derivatives. Bioorganic &
• Medicinal Chemistry Letter, 25, 3261- 3263, 2015.
• Senturk, M., Kufrevioglu, O.I. In vitroeffects of some nucleoside analogue drugs on enzyme activities of carbonic anhydrase isozymes I and II from human erythrocytes. Hacettepe Journal of Biology and Chemistry, 37, 289-294, 2009.
• Wilbur KM, Anderson NG. Electrometric and colorimetric determination of carbonic anhydrase. J Biol Chem., 176:
• -154, 1948.
• Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the
• principle of proteindye binding. Anal Biochem 72, 248-254, 1976.
• Drusano G.L., Standiford H.C., Plaisance K., Forrest A., Leslie J., Caldwell J. Absolute oral bioavailability of ciprofloxacin. Antimicrob Agents
• Chemother. 30, 444-446, 1986.
• Brunton Laurence L., Lazo John S., Parker K. eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics (11th ed.). New York: McGraw-Hill. 2005.
• Sharma M, Pathak S, Srivastava P. Prevalence and antibiogram of Extended Spectrum β-Lactamase (ESBL) producing Gram negative bacilli and further molecular characterization of ESBL producing Escherichia coli and Klebsiella spp. J Clin Diagn Res., 7, 2173-2177, 2013.
• Nair SK, Ludwig PA, Christianson DW. Two-site binding of phenol in the active site of human carbonic anhydrase II: structural implications for substrate association. J Am Chem Soc., 116, 3659-3660, 1994.