Microwave-assisted synthesis of N-benzylidene-4-fluoroaniline and N-benzylidene-4-Nitroaniline and their inhibitory activities on hCA isoenzymes

Year 2019, , 38 - 48, 16.03.2019

Hülya Çelik , Aynur Babagil

https://doi.org/10.21448/ijsm.479108

Cited By: 1

Abstract

In this study,
N-benzylidene-4-fluoroaniline (3a), N-benzylidene-4-nitroaniline (3b) as a
result of condensation of benzaldehyde (1) and 4-fluoroaniline (2a),
4-nitroaniline (2b) using a microwave method was synthesized. The structures of
the synthesized compounds were characterized by Fouirer Transform İnfrared
Spektrofotometre (FTIR spectroscopy), Nuclear Magnetic Resonance (NMR
spectroscopy) and elemental analysis methods. The prepared compounds were
tested for their inhibitory effects on carbonic anhydrase isoenzymes (hCA-I and
hCA-II). The results showed that the synthesized compounds 3a and 3b had a
strong inhibitory effect on hCA-I and hCA-II enzymes activity in vitro. By
testing these compounds in other CA isoenzymes, more effective CA inhibitors
can be formed. Thus, new therapeutic applications can be made for enzyme
activators in the near future.

Keywords

Schiff, microwave, fluoroaniline, nitroaniline

Microwave-assisted synthesis of N-benzylidene-4-fluoroaniline and N-benzylidene-4-Nitroaniline and their inhibitory activities on hCA isoenzymes

Abstract

In this study, N-benzylidene-4-fluoroaniline (3a), N-benzylidene-4-nitroaniline (3b) as a result of condensation of benzaldehyde (1) and 4-fluoroaniline (2a), 4-nitroaniline (2b) using a microwave method was synthesized. The structures of the synthesized compounds were characterized by Fouirer Transform İnfrared Spektrofotometre (FTIR spectroscopy), Nuclear Magnetic Resonance (NMR spectroscopy) and elemental analysis methods. The prepared compounds were tested for their inhibitory effects on carbonic anhydrase isoenzymes (hCA-I and hCA-II). The results showed that the synthesized compounds 3a and 3b had a strong inhibitory effect on hCA-I and hCA-II enzymes activity in vitro. By testing these compounds in other CA isoenzymes, more effective CA inhibitors can be formed. Thus, new therapeutic applications can be made for enzyme activators in the near future.

Keywords

Schiff, Microwave, Fluoroaniline, Nitroaniline, Inhibitor

References

• [1]. Pfeiffer, P., Breith, E., Lubbe, E., Tsumaki, T. (1933). Tricyclische Orthokondenzierte Nebenvolenzringe. Annalen Der Chemie., 503, 84-127.
• [2]. Oskay, E., (1990). Organik Kimya, Hacettepe Üniversitesi Yayınları A-42, 243, Ankara.
• [3]. Raman, N., Muthuraj, V., Ravichandran, S., Kulandaisamy, A. (2003). Synthesis, characterisation and electrochemical behaviour of Cu(II), Co(II), Ni(II) and Zn(II) complexes derived from acetylacetone and p-anisidine and their antimicrobial activity. Proc Indian Acad. Sci., 115-161.
• [4]. Helmut, S. (1976). Metal ions in biological systems, Marcel Dekker Inc, New York, 2-50s.
• [5]. Metzler, CM., Cahill, A., Metzler DE. (1980). Equilibriums and absorption spectra of Schiff bases. Journal of The American Chemical Society, 102 (19), 6075- 6082.
• [6]. Şekeroğlu, Z.A., Şekeroğlu, V. (2011). The in vitro alkaline comet assay in genetic toxicology. The Journal of Applied Behavioral Science, 5, 49-54.
• [7]. Kaya, B. (2003). Anti-genotoxic effect of ascorbic acid on mutagenic dose of three alkylating agents. Turkish Journal of Biology, 27, 241-246.
• [8]. Braconi, D., Sotgi, M., Millucci, L., Paffetti, A., Tasso, F., Alisi, C., Martini, S, Rappuoli, R., Lusini, P., Rosa, A., Rossi, C., Santucci, A. (2006). Comparative analysis of the effects of locally used herbicides and their active ingredients on a wild-type wine (Saccharomyces cerevisiae) strain. Journal of Agricural and Food Chemistry, 54, 3163-3172.
• [9]. Kappe, C.O. (2002). High-Speed Combinatorial Synthesis Utilizing Microwave Irradiation. Curr Opin Chem Biol., 6, 314-320.
• [10]. Kappe, C.O., Dallinger, D., Murphree, S.S. (2009). Practical Microwave Synthesis For Organic Chemists: Strategies, Instruments, And Protocols, Wiley-Vch, 299.
• [11]. Başarır, M. (2006). N-Sübstitüe Pirol Türevlerinin Mikrodalga Etkisi Altında Sentezi. Yüksek Lisans Tezi, Yıldız Teknik Üniversitesi Fen Bilimleri Enstitüsü, İstanbul, 82 S.
• [12]. Serdar, G., Demir, E., Bayrak, S., Sökmen, M. (2016). New Approaches for Effective Microwave Assisted Extraction of Caffeine and Catechins from Green Tea. International Journal of Secondary Metabolite, 3 (1), 3-13 https://dx.doi.org/10.21448/ijsm.240697
• [13]. Özturk, B, Yiğitarslan, S. (2017). Microwave Extraction of Gallic Acid Equivalent of Total Flavonoids from Nigella sativa. International Journal of Secondary Metabolite, 4 (3, Special Issue 1), 117-124. https://dx.doi.org/10.21448/ijsm.363838
• [14]. Shysh, S., Mazets, Z., Shutava, H., Sysha, O., Gorgun,Y. (2018). Electromagnetic radiation of low intensity as a factor of change of phenolic compounds content. International Journal of Secondary Metabolite, 5(3), 252 – 258 https://dx.doi.org/10.21448/ijsm.459102
• [15]. Serdar, G., Demir, E., Sökmen, M. (2017). Recycling of Tea Waste: Simple and Effective Separation of Caffeine and Catechins by Microwave Assisted Extraction (MAE). International Journal of Secondary Metabolite, 4(2), 78 - 89. https://dx.doi.org/10.21448/ijsm.288226
• [16]. Gedye, R., Smith, F., Westaway, K., Ali, H., Baldisera, L., Laberge, L., Roussel, J. (1986). The use of microwave ovens for rapid organic synthesis. Tetrahedron Letters 27(3), 279-282.
• [17]. Loferer, M. J., Tautermann, C.S., Loeffler, H.H., Liedl, K.R. (2003). Influence of backbone conformations of human carbonic anhydrase II on carbon dioxide hydration: hydration pathways and binding of bicarbonate. J. Am. Chem. Soc., 125, 8921–8927.
• [18]. Lindskog, S., Coleman, J.E., (1973). The Catalytic Mechanism of Carbonic Anhydrase. Proc. Nat. Acad. Sci., 70, (9), 2505-2508.
• [19]. Zimmerman, S.A., Ferry, J.G., Supuran, C.T. (2007). Inhibition of the archaeal beta-class (Cab) and gamma-class (Cam) carbonic anhydrases. Curr Top Med Chem., 9, 901-8.
• [20]. Demir, Y., Nadaroğlu, H., Demir, N. (2007). Purification and some properties of carbonic anhydrase from Elephas trogontherii(Steppe elephant) bone. J. Biochem., 3, 252-256.
• [21]. Demir Y., Demir N., Nadaroğlu H., Bakan E. (2000).Purification and Characterization of Carbonic Anhydrase From Bovine Erythrocyte Plasma Membrane. Prep. Biochem. Biothech., 30(1), 49-59, 2000.
• [22]. Demir N., Demir Y., Nadaroğlu H. (2001). Carbonic Anhydrase from Bovine Bone. Prep. Biochem. & Biotech., 31(1), 33-48.
• [23]. Sly, S.W., Peigi, Y. Hu., (1995). Human carbonic anhydrases and carbonic anhydrase deficiencies.Annu. Rev. Biochem., 64, 375-401.
• [24]. Demir Y., Nadaroğlu H., Demir N. (2005). Purification and Characterization of Carbonic Anhydrase From Bovine Stomach And Inhibitory Effects Of Some Chemical Substances On Enzyme Activities. J. Enzym. Inhib. Med. Chem., 20, 75-80.
• [25]. Bradford, M.M. (1976). A Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye Binding. Annal. Biochem., 72, 248-254.
• [26]. Altıntop M.D., Sever B., Çiftçi G.A., Kucukoglu K., Ozdemir A., Soleimani S.S., Nadaroglu H., Kaplancıklı Z.A. (2017). Eur. J. Med. Chem., 125, 190-196.
• [27]. Celik, H., Maman, M., Babagil, A. (2018). hCA isoenzyme inhibitory activities of Schiff bases derived from cinnamaldehyde and p-methoxycinnamaldehyde, Fresenius Environmental Bulletin, 27, 4469-4482.