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Determination of Inhibitory Effects of Thiazole Derivatives on Glutathione Reductase

Year 2021, Volume: 21 Issue: 6, 1315 - 1323, 31.12.2021
https://doi.org/10.35414/akufemubid.1019128

Abstract

Glutathione reductase enzyme (GR) is an important enzyme that catalyzes the formation of reduced glutathione (GSH) from oxidized glutathione (GSSG) and undertakes the task of maintaining the GSH/GSSG ratio in the body. This important task has made the inhibition of GR an important target in the treatment of many diseases. Therefore, it is very important to identify new GR inhibitors that can be used in drug design. In vitro anticancer studies of different 2-aminothiazole analogs have been shown to have potent inhibitory activities against a wide variety of human cancer cell lines, including lung, leukemia, breast, ovarian, kidney, melanoma, colon, CNS, and prostate. We investigated the inhibition effect of six thiazole derivatives, which contain an amino group at the C-2 position and used as a core structure in therapeutic applications, on GR isolated from fresh human erythrocytes. We determined the IC50 values of compounds 2-amino-4-(2,4-difluorophenyl) thiazole, 2-amino-4-(4-bromophenyl)thiazole, 2-amino-5-methyl-4-phenylthiazole, 2-amino-4-(5,6,7,8-tetrahydro-2-naphthyl)thiazole, 2-amino-4-(4-chlorophenyl)thiazole, 4-(3,4-difluorophenyl)-1,3-thiazole-2-amino 0,64 µM, 3,69 µM, 42,8 µM, 0,91 µM, 0,63 µM ve 21 µM respectively. Ki values were calculated as 0,006±0,00048 µM, 0,33±0,11 µM, 63,61±0,33 µM, 0,905±0,073 µM, 0,89±0,47 µM, 97,44 µM respectively. It was observed that 2-amino-4-(2,4-difluorophenyl) thiazole had the highest inhibition effect and 4-(3,4-difluorophenyl)-1,3-thiazol-2-amino had the lowest inhibition effect. It was observed that only 2-amino-4-(2,4-difluorophenyl)thiazole exhibited competitive inhibition, while other compounds exhibited non-competitive inhibition. Our study shows that these thiazole derivatives are potent GR inhibitors and can be used as a guide for the identification of new drug candidates.

References

  • Akkemik, E., Şentürk, M., Özgeriş, F.B., Taşer, P., Çiftçi, M., 2011. In vitro effects of some drugs on human erythrocyte glutathione reductase. Turkish Journal of Medical Sciences, 41(2), 235-241.
  • Akkemik, E., Güller, P., Bayındır, A., Budak, H., Çiftçi, M., 2012. Purification and characterization of glutathione S-transferase from turkey liver and inhibition effects of some metal ions on enzyme activity. Environmental Toxicology and Pharmacology, 34(3),1382-6689.
  • Alım, Z., Kılıç, D., Demir, Y., 2018. Some indazoles reduced the activity of human serum paraoxonase 1, an antioxidant enzyme: in vitro inhibition and molecular modeling studies. Archives of Physiology and Biochemistry, 125(5), 387-395.
  • Balaydın, H.T., Özil, M., Şentürk, M., 2018. Synthesis and glutathione reductase inhibitory properties of 5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one's aryl Schiff base derivatives. Archiv der Pharmazie, e1800086.
  • Chavan A. A. and Pai, N. R., 2007. Synthesis and biological activity of N-substituted-3-chloro-2-azetidinones. Molecules, 12(11), 2467–2477.
  • Demir, Y., Oruç, E., Topal, A., 2016. Carbonic Anhydrase Activity Responses and Histopathological Changes in Gill and Liver Tissues after Acute Exposure to Chromium in Brown Trout Juveniles. Hacettepe Journal of Biology and Chemistry, 44(4), 515–523.
  • Demir, Y., 2019. Purification of Glutathione Reductase from Human Erythrocytes: Inhibition Profile of Some Anti-Epileptic Drugs. Iğdır Üniversitesi Fen Bilimleri Enstitüsü Dergisi, 9(4), 2140-2147.
  • Erat, M., Şakiroğlu, H., Çiftçi, M., 2005. Effects of some antibiotics on glutathione reductase activities from human erythrocytes in vitro and from rat erythrocytes in vivo. Journal of Enzyme Inhibition and Medicinal Chemistry, 20, 69-74.
  • Gajdoˇs, P.,. Magdolen, P., Zahradn´ık, P., Folt´ınov´a, P., 2009. New conjugated benzothiazole-N-oxides: synthesis and biological activity. Molecules, 14(12), 5382–5388.
  • Ghaemmaghami, S., May, B.C.H., Renslo, A.R., Prusiner, S.B., 2010. Discovery of 2-aminothiazoles as potent antiprion compounds. Journal of Virology, 84(7), 3408–3412.
  • Gorczynski, M.J., Leal, R.M., Mooberry, S.L., Bushweller, J.H., Brown, M.L., 2004. Synthesis and evaluation of substituted 4-aryloxy- and 4-arylsulfanyl- phenyl-2-aminothiazolesas inhibitors of human breast cancer cell proliferation. Bioorganic and Medicinal Chemistry, 12(5), 1029–1036.
  • Işık, M., Demir, Y., Kırıcı M., Demir, R., Şimşek F., Beydemir, Ş., 2015. Changes in the anti-oxidant system in adult epilepsy patients receiving anti-epileptic drugs. Archives of Physiology and Biochemistry, 121, 97–102.
  • Karabulut, H., Gülay, M.Ş., 2016. Serbest radikaller. MAKÜ Sağlık Bilimleri Enstitüsü Dergisi, 4(1), 50-59.
  • Kaur, H., Kumar, S., Singh, I., Saxena K.K., Kumar, A., 2010. Synthesis, characterization and biological activity of various substituted benzothiazole derivatives. Digest Journal of Nanomaterials & Biostructures, 5(1), 67–76.
  • Kayagil, I., Demirayak, S., 2009. Synthesis and anticancer activities of some thiazole derivatives. Phosphorus, Sulfur and Silicon and the Related Elements, 184(9), 2197–2207.
  • Kesicki, E.A., Bailey, M.A., Ovechkina Y., Early, J.V., Alling, T., Bowman, J., Zuniga, E.S., Dalai, S., Kumar, N., Masquelin, T., Hipsking, P.A., Odingo, J.O., Parish, T., 2016. Synthesis and evaluation of the 2-aminothiazoles as anti-tubercular agents. Plos One, 11(5).
  • Khalifa, M.E., 2018. Recent developments and biological activities of 2-aminothiazole derivatives. Acta Chimica Slovenica, 65(1), 1-22.
  • Kumar, G.V.S., Rajendraprasad Y., Mallikarjuna, B.P., Chandrashekar, S.M., Kistayya, C., 2010. Synthesis of some novel 2-substituted-5-[isopropylthiazole] clubbed 1,2,4-triazole and 1,3,4-oxadiazoles as potential antimicrobial and antitubercular agents. European Journal of Medicinal Chemistry, 45(5), 2063–2074.
  • Kumar, K., Sagar, S., Esau, L., Kaur, M., Kumar, V., 2012. Synthesis of novel 1H-1,2,3- triazole tethered C-5 substituted uracil-isatin conjugates and their cytotoxic evaluation. European Journal of Medicinal Chemistry, 58, 153-159.
  • Lia, X, Ni, M, Xu, X, Chen, W, 2020. Characterisation of naturally occurring isothiocyanates as glutathione reductase inhibitors. Journal Of Enzyme Inhıbıtıon And Medıcınal Chemıstry, 35(1), 1773–1780. https://doi.org/10.1080/14756366.2020.1822828.
  • Lin, P., Hou, R., Wang, H.,, Kang,, I., Chen, L., 2009. Efficient Synthesis of 2-Aminothiazoles and Fanetizole in Liquid PEG-400 at Ambient Conditions. Journal of the Chinese Chemical Society, 56(3), 455–458.
  • Masoudi, N.A., Pfleiderer, W., Pannecouque, C., 2014. Nitroimidazoles part 7. synthesis and anti-HIV activity of new 4- nitroimidazole derivatives. Zeitschrift f¨ur Naturforschung B, 67(8), 835–842.
  • Nadeem, S., Arpana, R., Suroor A.K., Haque, S.E., Arshad, M.F., Ahmed, S., Ahsan, W., 2009. Synthesis and preliminary screening of benzothiazol-2-yl thiadiazole derivatives for anticonvulsant activity. Acta Pharmaceutica, 59(4), 441–451.
  • Oh, C.H., Cho, H.W., Baek, D., Cho, J.H., 2002. Synthesis and antibacterial activity of 1𝛽-methyl-2-(5-substituted thiazole pyrrolidin-3-ylthio) carbapenem derivatives. European Journal of Medicinal Chemistry, 37, 743–754.
  • Priyanka, Neeraj, K.S., Keshari, K.J., 2010. Benzothiazole: the molecule of diverse biological activities. International Journal of Current Pharmaceutical Research, 2, 1.
  • Samadhiya, P., Sharma, R., Srivastava, S.K., Srivastava, S.D., 2012. Synthesis of 2-oxoazetidine derivatives of 2-aminothiazole and their biological activity. Journal of the Serbian Chemical Society, 77(5), 599–605.
  • Siddiqui, H.L., Zia-Ur-Rehman, M., Ahmad, N., Weaver, G.W., Lucas, P.D., 2007. Synthesis and antibacterial activity of bis[2- amino-4-phenyl-5-thiazolyl] disulfides. Chemical and Pharmaceutical Bulletin, 55(7), 1014–1017.
  • Singh, H. P., Sharma, C. S. Gautam, C. P., 2009. Synthesis and pharmacological screening of some novel 2-arylhydrazino and 2-aryloxy-pyrimido [2,1-b] benzothiazole derivatives. American-Eurasian Journal of Scientific Research, 4(4), 222–228.
  • Sonwane, S.K., and Srivastava, S.D., 2008. Synthesis and biological significance of 2-amino-4-phenyl-1,3-thiazole derivatives. Proceedings of the National Academy of Sciences, India, 78(2), 129–136.
  • Srivastava, S.K., Yadav, R., Srivastava, S.D., 2004. Synthesis and biological activity of 4-oxothiazolidines and their 5-arylidenes. Indian Journal of Chemistry, l. 43B(2), 399–405.
  • Taslimi, P., Aslan, H.E., Demir, Y., Oztaskin, N., Maraş, A., Gülçin, İ., Beydemir, S., Göksu, S., 2018. Diarylmethanon, bromophenol and diarylmethane compounds: Discovery of potent aldose reductase, α-amylase and α-glycosidase inhibitors as new therapeutic approach in diabetes and functional hyperglycemia. International Journal of Biological Macromolecules, 119, 857-863.
  • Tapia, R.A., Prieto, Y., Pautet F., Walchshofer, N., Fillion, H., Fenet B., Sarciron, M.E., 2003. Synthesis and antiprotozoal evaluation of benzothiazolopyrroloquinoxalinones, analogues of kuanoniamine A. Bioorganic and Medicinal Chemistry, 11(16), 3407–3412.

Tiyazol Türevlerinin Glutatyon Redüktaz Üzerindeki İnhibitör Etkilerinin Belirlenmesi

Year 2021, Volume: 21 Issue: 6, 1315 - 1323, 31.12.2021
https://doi.org/10.35414/akufemubid.1019128

Abstract

Glutatyon redüktaz (GR), oksitlenmiş glutatyondan (GSSG) indirgenmiş glutatyonun (GSH) geri kazanımını katalize ederek GSH/GSSG oranını korumak için gerekli olan önemli bir antioksidan enzimdir. Bu hayati görev nedeniyle, GR'nin inhibisyonu birçok hastalığın tedavisinde önemli bir hedeftir, bu nedenle ilaç tasarımında yol gösterici olacak yeni GR inhibitörlerini belirlemeyi amaçladık. Daha önce, farklı 2-aminotiyazol analoglarının in vitro antikanser değerlendirme çalışmaları, meme, lösemi, akciğer, kolon, CNS, melanom, yumurtalık, böbrek ve prostat gibi çok çeşitli insan kanserli hücre hatlarına karşı güçlü ve seçici nanomolar inhibitör aktiviteleri sergiledikleri çalışmalarla doğrulandı. Çalışmamızda taze insan eritrositlerinden izole edilen GR üzerine, C-2 pozisyonunda amino grubu içeren ve terapötik uygulamalarda çekirdek yapı olarak kullanılan tiyazol türevi altı maddenin inhibisyon etkisini araştırdık. 2-amino-4-(2,4-diflorofenil)tiyazol, 2-amino-4-(4-bromofenil)tiyazol, 2-amino-5-metil-4-feniltiyazol, 2-amino-4-(5,6) ,7,8-tetrahidro-2-naftil)tiyazol, 2-amino-4-(4-klorofenil)tiyazol, 4-(3,4-diflorofenil)-1,3-tiyazol-2-amino bileşiklerinin sırasıyla IC50 değerleri 0,64 µM, 3,69 µM, 42,8 µM, 0,91 µM, 0,63 µM ve 21 µM olarak belirledik. Ki değerleri ise sırasıyla 0,006±0,00048 µM, 0,33±0,11 µM, 63,61±0,33 µM, 0,905±0,073 µM, 0,89±0,47 µM, 97,44 µM olarak hesaplandı. En yüksek inhibisyon etkisini 2-amino-4-(2,4-diflorofenil) tiyazol, en düşük inhibisyon etkisini ise 4-(3,4-diflorofenil)-1,3-tiyazol-2-aminonun gösterdiği görüldü. Sadece 2-Amino-4-(2,4-diflorofenil) tiyazolün yarışmalı inhibisyon sergilediği, diğer bileşiklerin yarışmasız inhibisyon sergilediği görüldü. Çalışmamız,bu tiyazol türevlerinin güçlü GR inhibitörleri olduğunu, yeni ilaç adayların belirlenmesi için yol gösterici olarak kullanılabileceğini göstermektedir.

References

  • Akkemik, E., Şentürk, M., Özgeriş, F.B., Taşer, P., Çiftçi, M., 2011. In vitro effects of some drugs on human erythrocyte glutathione reductase. Turkish Journal of Medical Sciences, 41(2), 235-241.
  • Akkemik, E., Güller, P., Bayındır, A., Budak, H., Çiftçi, M., 2012. Purification and characterization of glutathione S-transferase from turkey liver and inhibition effects of some metal ions on enzyme activity. Environmental Toxicology and Pharmacology, 34(3),1382-6689.
  • Alım, Z., Kılıç, D., Demir, Y., 2018. Some indazoles reduced the activity of human serum paraoxonase 1, an antioxidant enzyme: in vitro inhibition and molecular modeling studies. Archives of Physiology and Biochemistry, 125(5), 387-395.
  • Balaydın, H.T., Özil, M., Şentürk, M., 2018. Synthesis and glutathione reductase inhibitory properties of 5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one's aryl Schiff base derivatives. Archiv der Pharmazie, e1800086.
  • Chavan A. A. and Pai, N. R., 2007. Synthesis and biological activity of N-substituted-3-chloro-2-azetidinones. Molecules, 12(11), 2467–2477.
  • Demir, Y., Oruç, E., Topal, A., 2016. Carbonic Anhydrase Activity Responses and Histopathological Changes in Gill and Liver Tissues after Acute Exposure to Chromium in Brown Trout Juveniles. Hacettepe Journal of Biology and Chemistry, 44(4), 515–523.
  • Demir, Y., 2019. Purification of Glutathione Reductase from Human Erythrocytes: Inhibition Profile of Some Anti-Epileptic Drugs. Iğdır Üniversitesi Fen Bilimleri Enstitüsü Dergisi, 9(4), 2140-2147.
  • Erat, M., Şakiroğlu, H., Çiftçi, M., 2005. Effects of some antibiotics on glutathione reductase activities from human erythrocytes in vitro and from rat erythrocytes in vivo. Journal of Enzyme Inhibition and Medicinal Chemistry, 20, 69-74.
  • Gajdoˇs, P.,. Magdolen, P., Zahradn´ık, P., Folt´ınov´a, P., 2009. New conjugated benzothiazole-N-oxides: synthesis and biological activity. Molecules, 14(12), 5382–5388.
  • Ghaemmaghami, S., May, B.C.H., Renslo, A.R., Prusiner, S.B., 2010. Discovery of 2-aminothiazoles as potent antiprion compounds. Journal of Virology, 84(7), 3408–3412.
  • Gorczynski, M.J., Leal, R.M., Mooberry, S.L., Bushweller, J.H., Brown, M.L., 2004. Synthesis and evaluation of substituted 4-aryloxy- and 4-arylsulfanyl- phenyl-2-aminothiazolesas inhibitors of human breast cancer cell proliferation. Bioorganic and Medicinal Chemistry, 12(5), 1029–1036.
  • Işık, M., Demir, Y., Kırıcı M., Demir, R., Şimşek F., Beydemir, Ş., 2015. Changes in the anti-oxidant system in adult epilepsy patients receiving anti-epileptic drugs. Archives of Physiology and Biochemistry, 121, 97–102.
  • Karabulut, H., Gülay, M.Ş., 2016. Serbest radikaller. MAKÜ Sağlık Bilimleri Enstitüsü Dergisi, 4(1), 50-59.
  • Kaur, H., Kumar, S., Singh, I., Saxena K.K., Kumar, A., 2010. Synthesis, characterization and biological activity of various substituted benzothiazole derivatives. Digest Journal of Nanomaterials & Biostructures, 5(1), 67–76.
  • Kayagil, I., Demirayak, S., 2009. Synthesis and anticancer activities of some thiazole derivatives. Phosphorus, Sulfur and Silicon and the Related Elements, 184(9), 2197–2207.
  • Kesicki, E.A., Bailey, M.A., Ovechkina Y., Early, J.V., Alling, T., Bowman, J., Zuniga, E.S., Dalai, S., Kumar, N., Masquelin, T., Hipsking, P.A., Odingo, J.O., Parish, T., 2016. Synthesis and evaluation of the 2-aminothiazoles as anti-tubercular agents. Plos One, 11(5).
  • Khalifa, M.E., 2018. Recent developments and biological activities of 2-aminothiazole derivatives. Acta Chimica Slovenica, 65(1), 1-22.
  • Kumar, G.V.S., Rajendraprasad Y., Mallikarjuna, B.P., Chandrashekar, S.M., Kistayya, C., 2010. Synthesis of some novel 2-substituted-5-[isopropylthiazole] clubbed 1,2,4-triazole and 1,3,4-oxadiazoles as potential antimicrobial and antitubercular agents. European Journal of Medicinal Chemistry, 45(5), 2063–2074.
  • Kumar, K., Sagar, S., Esau, L., Kaur, M., Kumar, V., 2012. Synthesis of novel 1H-1,2,3- triazole tethered C-5 substituted uracil-isatin conjugates and their cytotoxic evaluation. European Journal of Medicinal Chemistry, 58, 153-159.
  • Lia, X, Ni, M, Xu, X, Chen, W, 2020. Characterisation of naturally occurring isothiocyanates as glutathione reductase inhibitors. Journal Of Enzyme Inhıbıtıon And Medıcınal Chemıstry, 35(1), 1773–1780. https://doi.org/10.1080/14756366.2020.1822828.
  • Lin, P., Hou, R., Wang, H.,, Kang,, I., Chen, L., 2009. Efficient Synthesis of 2-Aminothiazoles and Fanetizole in Liquid PEG-400 at Ambient Conditions. Journal of the Chinese Chemical Society, 56(3), 455–458.
  • Masoudi, N.A., Pfleiderer, W., Pannecouque, C., 2014. Nitroimidazoles part 7. synthesis and anti-HIV activity of new 4- nitroimidazole derivatives. Zeitschrift f¨ur Naturforschung B, 67(8), 835–842.
  • Nadeem, S., Arpana, R., Suroor A.K., Haque, S.E., Arshad, M.F., Ahmed, S., Ahsan, W., 2009. Synthesis and preliminary screening of benzothiazol-2-yl thiadiazole derivatives for anticonvulsant activity. Acta Pharmaceutica, 59(4), 441–451.
  • Oh, C.H., Cho, H.W., Baek, D., Cho, J.H., 2002. Synthesis and antibacterial activity of 1𝛽-methyl-2-(5-substituted thiazole pyrrolidin-3-ylthio) carbapenem derivatives. European Journal of Medicinal Chemistry, 37, 743–754.
  • Priyanka, Neeraj, K.S., Keshari, K.J., 2010. Benzothiazole: the molecule of diverse biological activities. International Journal of Current Pharmaceutical Research, 2, 1.
  • Samadhiya, P., Sharma, R., Srivastava, S.K., Srivastava, S.D., 2012. Synthesis of 2-oxoazetidine derivatives of 2-aminothiazole and their biological activity. Journal of the Serbian Chemical Society, 77(5), 599–605.
  • Siddiqui, H.L., Zia-Ur-Rehman, M., Ahmad, N., Weaver, G.W., Lucas, P.D., 2007. Synthesis and antibacterial activity of bis[2- amino-4-phenyl-5-thiazolyl] disulfides. Chemical and Pharmaceutical Bulletin, 55(7), 1014–1017.
  • Singh, H. P., Sharma, C. S. Gautam, C. P., 2009. Synthesis and pharmacological screening of some novel 2-arylhydrazino and 2-aryloxy-pyrimido [2,1-b] benzothiazole derivatives. American-Eurasian Journal of Scientific Research, 4(4), 222–228.
  • Sonwane, S.K., and Srivastava, S.D., 2008. Synthesis and biological significance of 2-amino-4-phenyl-1,3-thiazole derivatives. Proceedings of the National Academy of Sciences, India, 78(2), 129–136.
  • Srivastava, S.K., Yadav, R., Srivastava, S.D., 2004. Synthesis and biological activity of 4-oxothiazolidines and their 5-arylidenes. Indian Journal of Chemistry, l. 43B(2), 399–405.
  • Taslimi, P., Aslan, H.E., Demir, Y., Oztaskin, N., Maraş, A., Gülçin, İ., Beydemir, S., Göksu, S., 2018. Diarylmethanon, bromophenol and diarylmethane compounds: Discovery of potent aldose reductase, α-amylase and α-glycosidase inhibitors as new therapeutic approach in diabetes and functional hyperglycemia. International Journal of Biological Macromolecules, 119, 857-863.
  • Tapia, R.A., Prieto, Y., Pautet F., Walchshofer, N., Fillion, H., Fenet B., Sarciron, M.E., 2003. Synthesis and antiprotozoal evaluation of benzothiazolopyrroloquinoxalinones, analogues of kuanoniamine A. Bioorganic and Medicinal Chemistry, 11(16), 3407–3412.
There are 32 citations in total.

Details

Primary Language Turkish
Subjects Chemical Engineering
Journal Section Articles
Authors

Arzu Öztürk Kesebir 0000-0003-2603-7509

Publication Date December 31, 2021
Submission Date November 4, 2021
Published in Issue Year 2021 Volume: 21 Issue: 6

Cite

APA Öztürk Kesebir, A. (2021). Tiyazol Türevlerinin Glutatyon Redüktaz Üzerindeki İnhibitör Etkilerinin Belirlenmesi. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi, 21(6), 1315-1323. https://doi.org/10.35414/akufemubid.1019128
AMA Öztürk Kesebir A. Tiyazol Türevlerinin Glutatyon Redüktaz Üzerindeki İnhibitör Etkilerinin Belirlenmesi. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi. December 2021;21(6):1315-1323. doi:10.35414/akufemubid.1019128
Chicago Öztürk Kesebir, Arzu. “Tiyazol Türevlerinin Glutatyon Redüktaz Üzerindeki İnhibitör Etkilerinin Belirlenmesi”. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi 21, no. 6 (December 2021): 1315-23. https://doi.org/10.35414/akufemubid.1019128.
EndNote Öztürk Kesebir A (December 1, 2021) Tiyazol Türevlerinin Glutatyon Redüktaz Üzerindeki İnhibitör Etkilerinin Belirlenmesi. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi 21 6 1315–1323.
IEEE A. Öztürk Kesebir, “Tiyazol Türevlerinin Glutatyon Redüktaz Üzerindeki İnhibitör Etkilerinin Belirlenmesi”, Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi, vol. 21, no. 6, pp. 1315–1323, 2021, doi: 10.35414/akufemubid.1019128.
ISNAD Öztürk Kesebir, Arzu. “Tiyazol Türevlerinin Glutatyon Redüktaz Üzerindeki İnhibitör Etkilerinin Belirlenmesi”. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi 21/6 (December 2021), 1315-1323. https://doi.org/10.35414/akufemubid.1019128.
JAMA Öztürk Kesebir A. Tiyazol Türevlerinin Glutatyon Redüktaz Üzerindeki İnhibitör Etkilerinin Belirlenmesi. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi. 2021;21:1315–1323.
MLA Öztürk Kesebir, Arzu. “Tiyazol Türevlerinin Glutatyon Redüktaz Üzerindeki İnhibitör Etkilerinin Belirlenmesi”. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi, vol. 21, no. 6, 2021, pp. 1315-23, doi:10.35414/akufemubid.1019128.
Vancouver Öztürk Kesebir A. Tiyazol Türevlerinin Glutatyon Redüktaz Üzerindeki İnhibitör Etkilerinin Belirlenmesi. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi. 2021;21(6):1315-23.