Effects of some thio-crown ethers on human erythrocyte carbonic anhydrase I-II isozymes activities

Öz

Carbonic Anhydrases, a member of the class of metalloenzymes, catalyze the conversion of carbon dioxide to bicarbonate and proton. The inhibition or activation of carbonic anhydrases having many isoenzymes is of great physiological importance. That's why we have purified carbonic anhydrase I and II isoenzymes from human erythrocytes. On the activities of the purified enzymes we investigated that effects some thioether (1,10-dithia-18-crown-6 (B1), 1,7-dithia-15-crown-5 (B2), 1,7-dithia-12- (B3), 1,7-dithia-18-crown-6 (B4), 1,10-dithia-21-crown-7 (B5) and 1,4-dithia-12-crown-B6) derivatives in in vitro conditions. B1 and B5 did not show any regular effect on both isoenzyme activity. The best activation effect has been the B2 compound for both isoenzymes.

Anahtar Kelimeler

• Carbonic anhydrases,thio crown,activation

İnsan karbonik anhidraz I,II izoenzim aktiviteleri üzerine bazı tiyocrown eterlerin etkisi

Öz

Metalo enzim sınıfının bir üyesi olan karbonik anhidrazlar karbondioksitin bikarbonata ve protona dönüşümünü katalizlerler. Bir çok izoenzime sahip olan karbonik anhidrazların inhibisyonu veya aktivasyonu fizyolojik açıdan oldukça önemlidir. Bu yüzden bizde çalışmamızda insan eritrositlerinden karbonik anhidraz I ve II izoenzimini saflaştırdık. Saflaştırdığımız enzim aktiviteleri üzerinde bazı tiyo eter türevlerinin (1,10- ditiyo-18-crown-6 (B1), 1,7-ditiyo-15-crown-5 (B2), 1,7- ditiyo -12-crown-4 (B3), 1,7- ditiyo-18-crown-6 (B4), 1,10-ditiyo-21-crown-7 (B5) and 1,4-ditiyo-12-crown-4 (B6)) etkilerini in vitro şartlarda araştırdık. B1 ve B5 her iki izoenzim aktivitesi üzerinde düzenli bir etki göstermezken, en iyi aktivasyon etkisini her iki izoenzim için B2 bileşiği (hCA I için AC₅₀ 25.27µM ve hCA II için AC₅₀32.74 µM) göstermiştir.

Anahtar Kelimeler

• Karbonik anhidraz,tiyocrown,aktivasyon

Kaynakça

1. Maren, T.H., Carbonic anhydrase; chemistry, physiology and inhibition, Phsiological Reviews, 47, 595-781, (1967).
2. Supuran, C.T., and Scozzafava, A., Carbonic Anhydrase Inhibitors, Current Medicinal Chemistry, 1, 61-97,(2001).
3. Nar, M., Rozmarinik asitin antioksidan kapasitesinin belirlenmesi ve insan karbonik anhidraz izoenzimleri (hCA-I VE hCA-II) üzerine inhibisyon etkisinin incelenmesi. Yüksek Lisans Tezi, Atatürk Üniversitesi, Fen Bilimleri Enstitüsü, Erzurum, (2011).
4. Supuran, C.T., Carbonic anhydrases: catalytic and inhibition mechanisms, distribution and physiological roles. In carbonic anhydrase. Its inhibitors and activators (Supuran, C.T., Scozzafara, A. and Conway, J., eds), CRC Press, London, 1-23, (2004).
5. Chegwidden, W.R., Edwards, Y. and Carter, N., The Carbonic anhydrase-new horizons molecular bases of inherited disease (Scriver, C.R., Beaudet, A.L., Sly, W.S., and Valle, D.) 8th Edition, 2165-2204, McGraw-Hill Education., Newyork, (2000).
6. Supuran, C.T., Scozzafava, A., Casini, A., Mincione, F., Menabuoni, L., Caproiu, M.T., Maganu, M. and Banciu, M.D., Carbonic anhydrase inhibitors: sulfonamides incorporating furan-thiophene- and pyrrole-carboxamido groups possess strong topical intraocular pressure lowering porperties as aqueous suspensions, Biororganic and Medicinal Chemistry, 8, 2145-2155, (2000).
7. Supuran, C.T., and Scozzafava, A., Carbonic Anhydrase Inhibitors, Current Medicinal Chemistry, 1, 61-97,(2001). De Simone, G. and Supuran, C.T., Antiobesity carbonic anhydrase inhibitors, Current Topics in Medicinal Chemistry, 7, 9, 879-84, (2007).
8. Wolfensberger, T.J., The role of carbonic anhydrase inhibitors in the management of macular edema, Documenta Ophthalmologica, 97: 387–397, (1999).

9. Pastorekova, S., Zatovicova,M., and Pastorek, J., Cancer-Associated Carbonic Anhydrases and Their Inhibition, Current Pharmaceutical Design, 14, 685-698, (2008).
10. Dilek, E., Activation of Two Different Drugs Used in Alzheimer’s Disease Treatment on Human Carbonic Anhydrase Isozymes I and II Activity: an In Vitro Study, Turkish Journal of Pharmaceutical Sciences, 14, 2, 164-168, (2017).
11. Aggarwal, M., Kondeti, B. and McKenna, R., Anticonvulsant/antiepileptic carbonic anhydrase inhibitors: a patent review, Expert Opinion on Therapeutic Patents, 23, 6, 717-24, (2013).
12. Roth, D. E., Venta,P. J., Tashian, R. E. and Sly, W. S., Molecular basis of human carbonic anhydrase II deficiency, National Academy of Sciences of the United States of America, 89, 5, 1804–8, (1992).
13. DeCoursey, T.E., Hypothesis: do voltage-gated H(+) channels in alveolar epithelial cells contribute to CO(2) elimination by the lung?, American Journal of Physiology - Cell Physiology, 278, 1, C1–C10, (2000).
14. Rousselle, A.V., and Heymann, D., Osteoclastic acidification pathways during bone resorption, Bone, 30, 4, 533–540, (2002).
15. Sun, M.K., and Alkon, D.L., Carbonic anhydrase gating of attention: memory therapy and enhancement, Trends in Pharmacological Sciences, 23, 2, 83–9, (2002).
16. Alper, S.L., Genetic diseases of acid-base transporters., Annual Review of Physiology, 64, 899–923, (2002).
17. Supuran, C.T., Carbonic anhydrases: novel therapeutic applications for inhibitors and activators, Nature Reviews Drug Discoveryvol, 7, 2, 168–81, (2008).
18. Kiraz, A., Yeni tür Schiff bazı taç eter ligandlarının sentezi, kompleksleri ve yapılarının incelenmesi”, Doktora Tezi, Çanakkale Onsekiz Mart Üniversitesi Fen Bilimleri Enstitüsü, Çanakkale, (2008).
19. Bulut, N.V., Taç eter türevi bir makrosiklik bileşik kullanılarak değişik matrikslerde altın’ın zenginleştirilmesi ve spektrofotometrik tayini”, Doktora Tezi, Karadeniz Teknik Üniversitesi Fen Bilimleri Enstitüsü, Trabzon, (2009).
20. Xiao, L., Molecular characterization of drug/drug carrier interaction through investigation on a crown ether/ cation system,686, University of Wisconsin--Madison, (2006 ).
21. Darwish, I.A. and Uchegbu, I.F., The evaluation of crown ether based niosomes as cation containing and cation sensitive drug delivery systems, International Journal of Pharmaceutics, 159, 207–213, (1997).
22. Dumont, B., Joly, J.P., Chapleur, Y. and Marsura., A., New Oligosaccharidic Crown Ethers as Potential Drug-Targetting Vectors: Synthesis & Biological Evaluation. Bioorganic and Medicinal Chemistry Letters, 4, 1123–1126, (1994).
23. Coppola, C., Simeone, L., Trotta, R., De Napoli, L., Randazzo, A. and Montesarchio, D., Synthesis and NMR characterization of a novel crown-ether ring-fused uridine analogue. Tetrahedron, 66, 6769–6774,(2010).
24. Çiçek, B. and Yıldız, A., Synthesis, Metal Ion Complexation and Computational Studies of Thio Oxocrown Ethers, Molecules 16, 8670-8683,(2011).
25. Huyut, Z., Beydemir, S.˙and Gülçin, I., Inhibition properties of some flavonoids on carbonic anhydrase I and II isoenzymes purified from human erythrocytes., Journal of Biochemical and Molecular Toxicology, 21930, (2017).
26. Laemmli, U.K., Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680–5,(1970).
27. Verpoorte, J., Mehta, S. and Edsall, J.T., Esterase activities of human carbonic anhydrases B and C. The Journal of Biological Chemistry, 242, 4221–4229, (1967).
28. Akkemik, E., Camadan, Y., Cicek, B., Calisir, U. and Onbasioglu, Z., The determination of the carbonic anhydrases activators, The FEBS Journal, 283: P-09.02.2-020, (2016).
29. Çiçek, B., and Çalışır, Ü., The Investigation of Complexation Properties and Hard-Soft Acid-Base Relationship Between Thiacrown Ethers and Metal Ions, Letters in Organic Chemistry, 13, 572–577, (2016).
30. Shelton, J.B. and Chegwidden, W.R., Activation of carbonic anhydrase III by phosphate, Biochemical Society Transactionsvol, 16, 5, 853-854,(1988).
31. Banciu, C. and Puscas, I., Carbonic Anhydrase And Modulation of Physiologic And Pathologic Processes In the Organism: Enzime [sic] Activators And Inhibitors, 593, Timisoara: Editura Helicon, 1994.
32. Scozzafava, A., Briganti, F., Ilies, M.A. and Supuran, C.T.,Carbonic Anhydrase Inhibitors: Synthesis of Membrane-Impermeant Low Molecular Weight Sulfonamides Possessing in Vivo Selectivity for the Membrane-Bound versus Cytosolic Isozymes I, Journal of Medicinal Chemistry, 43, 2, 292–300, (2000).
33. Supuran, C., Scozzafava, T. and. Casini, A., Carbonic anhydrase inhibitors, Medicinal Research Reviews., 23, 2,146–89, (2003).
34. Silverman, D.N.,Tu, C. and Wynns, G.C., Proton transfer between hemoglobin and the carbonic anhydrase active site, The Journal of Biological Chemistry., 253, 8, 2563–2567, (1978).