2-Aminopiridin ile (E)-4-Okso-4-((4-sülfamoyilfenil)amino)büt-2-enoik Asitin Proton Transfer Tuzunun Sentezi, Metal Komplekslerinin Hazırlanması ve hCA I ve hCA II İzoenzimleri Üzerindeki İnhibisyon Özelliklerinin İncelenmesi

Yıl 2016, Cilt: 16 Sayı: 1, 41 - 53, 30.04.2015

Cengiz Yenikaya Halil İlkimen Mehmet Melih Demirel Burçin Ceyhan Ekrem Tunca Metin Bülbül

https://doi.org/10.5578/fmbd.24124

Cited By: 1

Öz

Bu çalışmada, ilk olarak sülfanilamit (sa) ve maleik anhidritin (mal) tepkimesinden (E)-3-(4-
sülfamoyilfenil)amino)büt-2-enoik asit (Hsamal) bileşiği sentezlenmiş ve sonra bu bileşiğin
2-aminopiridin (ap) ile proton transfer tuzu (Hapsamal) hazırlanmıştır. Bu tuzun Fe(II), Co(II),
Ni(II) ve Zn(II) geçiş metal kompleksleri sentezlenmiştir. Proton transfer tuzlarının yapısı
elementel analiz, 1H-NMR, 13C-NMR, FT-IR, UV-Vis metotları ile aydınlatılmıştır. Amorf halde
elde edilen geçiş metal komplekslerinin yapıları ise elementel analiz, ICP-OES, FT-IR, UV-Vis,
manyetik duyarlılık ve molar iletkenlik sonuçları dikkate alınarak önerilmiştir. Ayrıca,
sentezlenen maddelerin insan eritrosit hCA I ve hCA II izoenzimleri üzerindeki inhibisyon
etkilerini belirlemek üzere in vitro çalışmalar yapılmıştır. Yeni sentezlenen maddelerin
izoenzimlerin esteraz aktivitesini inhibe ettiği tespit edilmiştir. Bu maddelerin inhibisyon
değerlerinin kontrol bileşiği asetazolamid (AAZ) değerleri ile kıyaslanabilir büyüklükte olduğu
tespit edilmiştir

Anahtar Kelimeler

“Sülfamoyil Bileşikleri” “2-Aminopiridin” “Proton Transfer Tuzu” “Metal Kompleksleri” “Karbonik Anhidraz İnhibisyonu”

Kaynakça

• Aghabozorg, H., Manteghi, F. and Sheshmani, S., 2008. A brief review on structural concepts of novel supramolecular proton transfer compounds and their metal complexes, J Iran Chem. Soc., 5(2), 184-227.
• Allen, R.G., Pereira, L.S. Raes D. and Smith, M. 1998. Crop evapotranspiration: Guidelines for computing crop water requirements”, Irr and Drain, UN-FAO, Rome, Italy, pp 56.
• Ashok, M., Prasad, A.V.S.S. and Ravinder, V., 2007. Synthesis, Spectral Studies and Catalytic Activity of Ruthenium(II) Complexes with Organic Amide Ligands. J Braz. Chem. Soc. 18(8), 1492-1499.
• Bergmann, F. and Schapiro, D., 1942. Further acylation experiments with sulfanilamide and heterocyclic amines, J Org. Chem. 07 (5), 419- 423.
• Bulbul, M., Hisar, O., Beydemir, S., Ciftci, M. and Kufrevioğlu, O.İ., 2003. The in vitro and in vivo inhibitory effects of some sulfonamide derivatives on rainbow trout (Oncorhynchus mykiss) erythrocyte carbonic anhydrase activity. J Enzyme Inhib. Med. Chem. 18, 371– 375. Bywater, R.J., 1991. Sulfonamides and diaminopyrimidines. In: Veterinary Applied Pharmacology and Therapeutics, Eds: G. C. Brander, D. M. Pugh, R. J. Bywater, W. L. Jenkins, 5 th Ed, Baillere Tindali, London, 489- 494.
• Ceyhan, B., 2013. 2-Hidrojenbenzimidazol ile 4- okso-4-((4-sülfomoilfenil)amino)büt-2-enoik asit komplekslerinin hazırlanması ve kullanım alanlarının araştırılması. Yüksek Lisans Tezi, Dumlupınar Üniversitesi Enstitüsü. geçiş metal Fen Bilimleri
• Ciftci, M., Bulbul, M., Gul, M., Gumuştekin, K., Dane, Ş. and Suleyman, H., 2005. Effects of nicotine and Vitamin E on carbonic anhydrase activity in some rat tissues in vivo and in vitro. J Enzyme Inhib. Med. Chem. 20, 103–109.
• Cook, D. 1961. Vibrational spectra of pyridinium salt. Canadian J. Chem. 39(10), 2009-2024.
• Demirel, M.M., 2013. 2-Aminopiridin ile 4-okso-4- ((4-sülfomoilfenil)amino)büt-2-enoik tuzunun sentezi, geçiş metal komplekslerinin hazırlanması araştırılması. Yüksek Lisans Tezi, Dumlupınar Üniversitesi Fen Bilimleri Enstitüsü. asit ve kullanım alanlarının
• Fuhrmann, H., Brenner, S., Arndt P., and Kempe, R., 1996. Octahedral Group 4 Metal Complexes That Aminopyridinato Structure, and Application in α-Olefin Oligo- and Polymerization. Inorg. Chem. 35, 6742- 6745 Amido, and Ligands:  Synthesis,
• Geary, W.J., 1971. The use of conductivity measurements in organic solvents for the characterisation of coordination compounds, Coor. Chem. Rev. 7(1), 81-122.
• Gowda, B.T., Jyothi, K. and Souza, J.D.D.Z., , 2002. Infrared arylsulphonamides, 4-X-C6H4SO2NH2 and i-X, j-YC6H3SO2NH2 (X = H; CH3; C2H5; F; Cl; Br; I or NO2 and i-X, j-Y = 2,3-(CH3)(2); 2,4-(CH3)(2); 2,5(CH3)(2); 2-CH3, 4-Cl; 2-CH3, 5-Cl; 3-CH3, 4- Cl; 2,4-Cl-2 or 3,4-Cl-2). Naturforsch 57a, 967- 973. spectra of
• Innocenti, A., Scozzafava, A., Parkkila, S., Pucceti, L., De Simone, G. and Supuran, C.T., 2008. Investigations of the esterase, phosphatase, and sulfatase activities of the cytosolic mammalian carbonic anhydrase isoforms I, II, and XIII with 4-nitrophenyl esters as substrates. Bioorg. Med. Chem. Lett. 18, 2267–2271.
• İlkimen, H., Yenikaya, C., Sarı, M., Bülbül, M., Tunca, E. and Süzen, Y. 2013. Synthesis and Characterization of a Proton Transfer Salt between Dipicolinic Acid and 2-Amino-6- Methylbenzothiazole and Its Complexes, and Their Inhibition Studies on Carbonic Anhydrase Isoenzymes. Polyhedron, 61 56- 64.
• Kempte, R., Brenner, S. and Arndt, P., 1996. Mononuclear Tris(aminopyridinato)zirconium Alkyl, Aryl, and Alkynyl Complexes. Organometallics 15, 1071–1074.
• Lah, N., Giester, J., Segedin, P. and Leban, I., 2001. Copper(II) aminopyridine. Synthesis, characterization and a study of the dimer–monomer equilibrium in acetonitrile solutions by VIS- spectroscopic titrations, New J Chem. 25, 753-759. 2- and microcalorimetric
• Lazarou, K.N., Perlepes, S.P., Psycharis, V. and Raptopoulou, C.P., 2008. Synthetic study of the ternary copper(II)/maleamate(-1)/1,10- phenanthroline Mononuclear, dinuclear and polymeric complexes. Polyhedron 27, 2131–2142.
• MacDonald, J.C., Dorrestein, P.C., Pilley, M.M., Foote, M.M., Lundburg, J.L., Henning, R.W., Schultz, A.J. and Manson, J.L.,, 2000. Design of layered coordination chemistry and hydrogen bonds, J Am. Chem. Soc., 122, 11692-11702.
• Mei, L., Ming, T.H., Rong, L.Q., Jie, S., Zhong, Y.S. and Liang, L.X., 2009. The synthesis of N–Zn, N–Cu complexes involving 2-amino pyridine and ethylenediamine ligands and application to the Henry reaction, J Chem. Sci. 121(4), 435– 440.
• Mistri, S., Zangrando, E. and Manna, S.C., 2013. Cu(II) dicarboxylate and N-donor neutral ligands: Synthesis, crystal structure, thermal behavior, DFT calculation and effect of aromatic compounds on their fluorescence. Inorg. Chim. Acta 405, 331–338. pyridine-2,6
• Netland, P.A., 2008, Glaucoma medical therapy, Oxford University Press Inc., 290 p.
• Poddar, R.K. and Agarwala, U., 1973. Reactions of Ru(PPh3)2Cl2 and [Ru(AsPh3)2Cl2]2 with various donor molecules. J Inorg. Nucl. Chem. 35, 3769-3779.
• Prescott, J.J. and Baggot, D.J., 1993. Antimicrobial therapy in veterinary medicine, International Book Distributing Co., India, 564-565.
• Raso, A.G., Fiol, J.J., Zafra, A.L., Cabrero, A., Mata, I. and Molins, E., 1999. Crystal structures of the N-salicylidene–L-serinatoaquacopper(II) monohydrate and its ternary derivative with 2-aminopyridine. Polyhedron 18, 871–878.
• Shah, A.I., Shukla, H.M., Shah. P.J. and Raj, D.S., 2012. Novel co-ordination polymers of 8- hydroxyquinoline. Elixir. Chem. Phys. 44 7378- 7381.
• Supuran, C.T., 2008. Carbonic anhydrases: novel therapeutic applications for inhibitors and activators. Nat. Rev. Drug. Discov. 7 168-181.
• Supuran, C.T., Briganti, F., Tilli, S., Chegwidden, W.R. and Scozzafava, A., 2000. Carbonic Anhidrase Inhibitors: Sulfonamide as Antitumor Agents, Bioorg. Med. Chem., 9, 703-714.
• Téllez, F., López-Sandoval, H., Castillo-Blum, S. E and Barba-Behrens, N., 2008. Coordination behavior of benzimidazole, 2-substituted benzimidazoles and benzothiazoles, towards transition metal ions. Arkivoc (v), 245-275.
• Verpoorte, J.A., Mehta, S. and Edsall, J.T., 1967. Esterase activities of human carbonic anhydrases B and C. J Biol. Chem. 242, 4221– 4229.
• Williams D.H. and Fleming I., 1989, Spectroscopic Methods in Organic Chemistry, 4th ed. revised, McGraw-Hill Book Company (UK) Limited.
• Yenikaya, C., İlkimen, H., Demirel, M.M., Ceyhan, B., Bülbül, M. and Tunca, E., 2016. Preparation of Two Maleic Acid Sulfonamide Salts And Their Cu(II) Complexes and Antiglaucoma Activity Studies, J 10.5935/0103-5053.20160051. Chem. Soc. DOI:
• Yenikaya, C., Poyraz, M., Sarı, M., Demirci, F., İlkimen, H. and Büyükgüngör, O., 2009. Synthesis, characterization and biological evaluation of a novel Cu(II) complex with the mixed ligands 2,6-pyridinedicarboxylicacid and 2-aminopyridine. Polyhedron, 28(16), 3526-3532.
• Yenikaya, C., Sarı, M., Bülbül, M., Ilkimen, H., Çelik, H. and Büyükgüngör, O., 2010. Synthesis, characterization and antiglaucoma activity of a novel proton transfer compound and a mixed-ligand Zn(II) complex, Bioorg. Med. Chem., 18(2), 930-938.
• Yenikaya, C., Sarı, M., Bülbül, M., Ilkimen, H., Çınar, B. and Büyükgüngör, O., 2011. Synthesis and characterization of two novel proton transfer compounds and their inhibition studies on Carbonic Anhydrase isoenzymes, J Enzyme Inhi. Med. Chem. 26(1), 104-114. Teşekkür
• Bu çalışmaya katkılarından dolayı Dumlupınar Üniversitesi Bilimsel Araştırma Projeleri Komisyonu’na teşekkür ederiz
• (Proje No: 2012/16).