Yeni 2-Metoksi-6-[(3-alkil/aril-4,5-dihidro-1H-1,2,4-triazol-5-on-4-il)-azometin]fenil Furan-2-karboksilat Türevlerinin Sentezi ve in vitro Antioksidan Aktiviteleri

Year 2020, Issue: 18, 1004 - 1011, 15.04.2020

Abdurrahman Gürbüz Muzaffer Alkan Sevda Manap Özlem Gürsoy Kol Gül Özdemir Haydar Yüksek

https://doi.org/10.31590/ejosat.656126

Abstract

1,2,4-Triazol ve 4,5-dihidro-1H-1,2,4-triazol-5-on halkası taşıyan heterosiklik bileşikler çok geniş bir spektrumda biyolojik aktivite göstermektedir. Schiff bazlarının ise boya, tekstil, kozmetik, analitik reaktifler, su iyileştirme ürünleri, petrol katkı maddeleri, sentetik polimer ürünleri, deri ve kağıt gibi doğal makromoleküler materyallerin iyileştirilmesi gibi çeşitli pratik uygulamaları bulunmaktadır. Ancak Schiff Bazlarının en önemli uygulama alanı ilaç kimyasıdır. Potansiyel biyolojik aktif 1,2,4-triazol halkası içeren Schiff bazlarının birçok hastalığın tedavisinde kullanılabilecek faydalı moleküllerin ve ileride hastalıkların tedavisinde kullanılabilecek ilaçların elde edilmesi ümit edilmektedir. Bu amaçla 3-alkil(aril)-4-amino-4,5-dihidro-1H-1,2,4-triazol-5-on’ların (1), 2-formil-6-metoksifenil furan-2-karboksilat (2) ile reaksiyonundan 2-metoksi-6-[(3-alkil/aril-4,5-dihidro-1H-1,2,4-triazol-5-on-4-il)-azometin]fenil furan-2-karboksilatlar (3) elde edilmiştir. Daha sonra 3 bileşiklerinin asetilasyon reaksiyonları incelenerek 2-metoksi-6-[(1-asetil-3-alkil/aril-4,5-dihidro-1H-1,2,4-triazol-5-on-4-il)-azometin]fenil furan-2-karboksilatlar (4) sentezlenmiştir. On dört yeni bileşiğin yapıları IR, 1H NMR, 13C NMR ve UV spektral verileri kullanılarak aydınlatılmıştır. Ayrıca, sentezlenen 3 ve 4 tipi yeni bileşiklerin üç farklı yöntemle (indirgeme gücü, serbest radikal giderme aktivitesi ve metal şelat aktivitesi) in vitro antioksidan özellikleri değerlendirilmiştir.

Keywords

Schiff bazı, Sentez, Asetilasyon, Antioksidan Aktivitesi

Supporting Institution

TÜBİTAK

Project Number

107T633

Thanks

Bu çalışma (107T633) no’lu proje kapsamında TÜBİTAK tarafından desteklenmiştir.

Synthesis and in vitro Antioxidant Activities of Novel 2-Methoxy-6-[(3-alkyl/aryl-4,5-dihydro-1H-1,2,4-triazol-5-on-4-yl)-azomethine]phenyl Furan-2-carboxylate Derivatives

Abstract

Heterocyclic compounds bearing 1,2,4-triazole and 4,5-dihydro-1H-1,2,4-triazole-5-one ring show a wide spectrum of biological activity. Schiff bases have various practical applications such as dyes, textile, cosmetics, analytical reagents, water treatment products, petroleum additives, synthetic polymer products, the improvement of natural macromolecular materials like leather and paper. However, the most important application area of Schiff Bases is pharmaceutical chemistry. It is hoped that Schiff bases containing a potentially biologically active 1,2,4-triazole ring will provide useful molecules that can be used in the treatment of many diseases and drugs that can be used in the treatment of future diseases. In this regard, new 2-methoxy-6-[(3-alkyl/aryl-4,5-dihydro-1H-1,2,4-triazol-5-on-4-yl)-azomethine]phenyl furan-2-carboxylates (3) were obtained from the reactions of 3-alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones (1) with 2-formyl-6-methoxyphenyl furan-2-carboxylate (2). Then, acetylation reactions of 3 compounds were examined and 2-methoxy-6-[(1-acetyl-3-alkyl/aryl-4,5-dihydro-1H-1,2,4-triazol-5-on-4-yl)-azomethine]phenyl furan-2-carboxylates (4) were synthesized. The structures of fourteen new compounds were characterized by IR, 1H NMR, 13C NMR and UV spectral data. Besides, in vitro antioxidant properties of the newly synthesized 3 and 4 type compounds were evaluated by three different methods (reduction power, free radical removal activity and metal chelate activity).

Keywords

Schiff base, 4, 5-Dihydro-1H-1, 2, 4-triazol-5-one, Syntheses, Acetylation, Antioxidant Activity

Project Number

107T633

References

• Aktas-Yokus, Ö., Yuksek, H., Manap, S., Aytemiz, F., Alkan, M., Beytur, M., Gürsoy-Kol, Ö. (2017). In-vitro biological activity of some new 1,2,4-triazole derivatives with their potentiometric titrations. Bulg. Chem. Commun., 49: 98-106.
• Ali, K.A., Ragab, E.A., Farghaly, TA, Abdalla, M.M. (2011). Synthesis of new functionalized 3-substituted [1,2,4]triazolo [4,3-a] pyrimidine derivatives: Potential antihypertensive agents. Acta Pol. Pharm., 68(2): 237-247.
• Alkan, M., Yüksek, H., Gürsoy-Kol, Ö., Calapoğlu, M. (2008). Synthesis, acidic and antioxidant properties of some novel 3,4-disubstituted-4,5-dihydro-1H-1,2,4-triazol-5-one derivatives, Molecules, 13: 107-121.
• Bahçeci, Ş., Yüksek, H., Ocak, Z., Köksal, C., Özdemir, M., (2002). Synthesis and non-aqueous medium titrations of some new 4,5-dihydro-1H-1,2,4-triazol-5-one derivative, Acta Chem. Slov., 49: 783-794.
• Blois, M. (1958). Antioxidant determinations by the use of a stable free radical. Nature, 181(4617): 1199-1200.
• Chidananda, N., Poojary, B., Sumangala, V., Kumari, N.S., Shetty, P., Arulmoli, T. (2012). Facile synthesis, characterization and pharmacological activities of 3,6-disubstituted 1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles and 5,6-dihydro-3,6-disubstituted-1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles. Eur. J. Med. Chem. 51: 124-136.
• Demirbas, N., Ugurluoglu, R., Demirbas. A. (2002). Synthesis of 3-alkyl(Aryl)-4-alkylidenamino-4,5-dihydro-1H-1,2,4-triazol-5-ones and 3-alkyl-4-alkylamino-4,5-dihydro-1H-1,2,4-triazol-5-ones as antitumor agents. Bioorg. Med. Chem., 10(12): 3717-3723.
• Dinis, T.C.P., Madeira, V.M.C., Almeida, L.M. (1994). Action of phenolic derivatives (Acetaminophen, salicylate, and 5-aminosalicylate) as inhibitors of membrane lipid peroxidation and as peroxyl radical scavengers. Arch. Biochem. Biophys, 315(1): 161-169.
• Gürsoy-Kol, Ö., Ayazoglu, E. (2017). Antioxidant activities and acidic properties of some novel 4-[3,4-di-(4-nitrobenzoxy)-benzylidenamino]-4,5-dihydro-1H-1,2,4-triazol-5-one derivatives. Arab. J. Chem., 10(S2): S2881-S2889.
• Gürsoy Kol, Ö. Yüksek, H., (2010). Synthesis and in-vitro antioxidant evaluation of some novel 4,5-dihydro-1H-1,2,4-triazol-5-one derivatives, E-J. Chem., 7(1): 123-136.
• Henen, M.A., El Bialy, S.A.A., Goda, F.E., Nasr, M.N.A., Eisa, H.M. (2012). [1,2,4]Triazolo[4,3-a]quinoxaline: Synthesis, antiviral, and antimicrobial activities. Med. Chem. Res., 21(9): 2368-2378.
• Hussain, H.H, Babic, G., Durst, T, Wright, J.S., Flueraru, M., Chichirau, A., Chepelev, L.L. (2003). Development of novel antioxidants: Design, synthesis, and reactivity. J. Org. Chem., 68(18): 7023-7032.
• Ikizler, A., Yüksek, H. (1993). Acetylation of 4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones. Org. Prep. Proc. Int., 25(1): 99-105.
• Ikizler, A.A., Johansson, C.B., Bekircan, O., Çelik, C. (1999). Synthesis and antibacterial activities of some 1,2,4-triazole derivatives. Acta Pol. Pharm. - Drug Res., 56(4): 283-288.
• Li, Z., Cao, Y., Zhan, P., Pannecouque, C., Balzarini, J., Clercq, E.De. (2013). Synthesis and anti-HIV evaluation of novel 1,2,4-triazole derivatives as potential non-nucleoside HIV-1 reverse transcriptase inhibitors. Lett. Drug Des. Discov., 10(1): 27-34.
• McClements, D., Decker, E. (2000). Lipid oxidation in oil-in-water emulsions: Impact of molecular environment on chemical reactions in heterogeneous food systems. J. Food Sci., 65(8): 1270-1282.
• Oyaizu, M. (1986). Studies on products of browning reaction. Antioxidative activities of products of browning reaction prepared from glucosamine. Japanese J. Nutr. Diet., 44(17): 307-315.
• Saadeh, H.A., Mosleh, I.M., Al-Bakri, A.G., Mubarak, M.S. (2010). Synthesis and antimicrobial activity of new 1,2,4-triazole-3-thiol metronidazole derivatives. Monats. Chem., 141(4): 471-478.
• Uzgören-Baran, A., Tel, B.C., Sarıgöl, D., Öztürk, E.I., Kazkayası, I., Okay, G., Ertan, M., Tozkoparan, B. (2012). Thiazolo[3,2-b]-1,2,4-triazole-5(6H)-one substituted with ibuprofen: Novel non-steroidal anti-inflammatory agents with favorable gastrointestinal tolerance. Eur. J. Med. Chem., 57: 398-406.
• Yüksek, H., Akyıldırım, O., Yola, M.L., Gürsoy-Kol, Ö., Çelebier, M., Kart, D. (2013). Synthesis, in vitro antimicrobial and antioxidant activities of some new 4,5-dihydro-1H-1,2,4-triazol-5-one derivative, Arch. Pharm., 346(6): 470-480.
• Yüksek, H., Üçüncü, O., Alkan, M., Ocak, Z., Bahçeci, Ş. (2005). Non-aqueous medium titrations of some new 4-benzylidenamino-4,5-dihydro-1H-1,2,4-triazol-5-one derivatives”, Molecules, 10: 961-970.