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Nitro grubu İçeren Bazı Maddelerin Glutatyon Redüktaz Enzimi Üzerindeki İnhibisyon Etkisinin İncelenmesi

Year 2019, Volume: 8 Issue: 4, 438 - 443, 31.12.2019

Abstract




Glutatyon redüktaz (Glutatyon: NADP+
oksidoredüktaz, EC 1.8.1.7; GR) düşük (GSH) veya yüksek molekül ağırlıklı
(GSSG) disülfit substratları ile indirgenmiş piridin nükleotidleri (NADPH)
arasında elekton transferini katalizler. GR inhibitörleri son zamanlarda
anti-sıtma ve kansere karşı faaliyetlerinin keşfedilmesi nedeniyle oldukça
popüler hale gelmiştir.




Enzimatik aktivite Beutler metodu
kullanılarak Spektrofotometre kullanılarak 25°C’de yapıldı. Ölçüm sistemi 100
mM Tris-HCl tamponunda (pH 8.0), 0,5 mM EDTA, 3,3 mM GSSG ve 0,1 mM NADPH içeriyordu.
Nitrobenzen (1), 3,5-Dinitrosalisilik
asit (2), (2,4-Dinitrofenil) ((4-(prop-1-en-2-yl)
sikloheks-1-enil)-metil) sulfan (3),
((7,7-dimetilbisiklo [2.2.1] heptan-1-il)metil)-(2,4-dinitrofenil)sulfan (4) ve ((2-kloro-7,7-dimetilbisiklo [2.2.1]
heptan-1-il)metil)-(2,4-dinitrofenil)sulfan (5) maddelerinin GR enzimi üzerindeki in vitro inhibisyon etkisi
incelendi.




İnhibisyon etkisi gösteren maddeler için %
aktivite-[I] grafikleri çizilerek IC50 değerleri bulunmuştur. Bu
maddelerin GR için IC50 değerlerinin mikromolar seviyesinde olduğu
gözlemlendi.



Supporting Institution

Ağrı İbrahim Çeçen Üniversitesi Bap

Project Number

ECZF.19.001

References

  • 1. Schirmer, RH, Krauth-Siegel, RL, Schulz, GE, (1989). Glutathione Reductase, John Wiley and Sons, New York, pp. 553-596.
  • 2. Kocaoglu, E, Talaz, O, Cavdar, H, Senturk, M, Supuran, CT, Ekinci, D. (2018). Determination of the inhibitory effects of N-methylpyrrole derivatives on glutathione reductase enzyme. Journal of Enzyme Inhibition and Medicinal Chemistry. 2018, 34, 51-54.
  • 3. Krauth-Siegel, RL, Bauer, H, Schirmer, RH. (2005). Dithiol proteins as guardians of the intracellular redox milieu in parasites: old and new drug targets in trypanosomes and malaria-causing plasmodia. Angewandte Chemie International Edition, 44, 690-715.
  • 4. Pastore, A, Federici, G, Bertini, E, Piemonte, F. (2003). Analysis of glutathione: implication in redox and detoxification. Clinical Chimica Acta, 333, 19-39.
  • 5. Perricone, C, De Carolis, C, Perricone, R. (2009). Glutathione: a key player in autoimmunity. Autoimmunity Reviews, 8, 697-701.
  • 6. Biot, C, Bauer, H, Schirmer, RH, Davioud-Charvet, E. (2004). 5-Substituted tetrazoles as bioisosteres of carboxylic acids. Bioisosterism and mechanistic studies on glutathione reductase inhibitors as antimalarials. Journal of Medicinal Chemistry, 47, 5972-5983.
  • 7. Grellier, P, Sarlauskas, J, Anusevicius, Z, Maroziene, A, Houee-Levin, C, Schrevel, J, et. al. (2001). Antiplasmodial activity of nitroaromatic and quinoidal compounds: Redox potential vs inhibition of erythrocyte glutathione reductase. Archives of Biochemistry and Biophysics, 393, 199-206.
  • 8. Zhao, Y, Seefeldt, T, Chen, W, Wang, X, Matthees, D, Hub,Y, et. al. (2009). Effects of glutathione reductase inhibition on cellular thiol redox state and related systems. Archives of Biochemistry and Biophysics, 485, 56-62.
  • 9. Ricci, G, De Maria, F, Antonini, G, Turella, P, Bullo, A, Stella, L, et al. (2005). 7-Nitro-2,1,3benzoxadiazole derivatives, a new class of suicide inhibitors for glutathione S-transferases. Mechanism of action of potential anticancer drugs. Journal of Biological Chemistry, 280, 26397-26405.
  • 10. Ascione, A, Cianfriglia, M, Dupuis, ML, Mallano, A, Sau, A, Pellizzari Tregno, F, et al. (2009). The glutathione S-transferase inhibitor 6-(7-nitro-2,1,3benzoxadiazol-4-ylthio)hexanol overcomes the MDR1P-glycoprotein and MRP1-mediated multidrug resistance in acute myeloid leukemia cells. Cancer Chemotherapy and Pharmacology, 64, 419-424.
  • 11. Pasello, M, Michelacci, F, Scionti, I, Hattinger, CM, Zuntini, M, Caccuri, AM, et al. (2008). Overcoming glutathione S-transferase P1-related cisplatin resistance in osteosarcoma. Cancer Research, 68, 6661-6668.
  • 12. Zhuo, R, Kosak, KM, Sankar, S, Wiles, ET, Sun, Y, Zhang, J, et al. (2014). Targeting Glutathione S-transferase M4 in Ewing sarcoma. Frontiers in Pediatrics, 83, 1-9.
  • 13. Tang, H, Yao, X, Yao, C, Zhao, X, Zuo, H, Li, Z. (2017). Anti-colon cancer effect of caffeic acid p-nitro-phenethyl ester in vitro and in vivo and detection of its metabolites. Scientific Reports, 7, 7599, 1-11.
  • 14. Noguchi, K, Uemura, H, Harada, M, Miura, T, Moriyama, M, Fukuoka, H, et al. (2001). Inhibition of PSA flare in prostate cancer patients by administration of flutamide for 2 weeks before initiation of treatment of slow-releasing LH-RH agonist. International Journal of Clinical Oncology, 6, 29-33.
  • 15. Olender, D, Żwawiak, J, Zaprutko, L. (2018). Multidirectional Efficacy of Biologically Active Nitro Compounds Included in Medicines. Pharmaceuticals, 11, 54, 1-29.
  • 16. Beutler E. (1984). Red Cell Metabolism. A manual of biochemical methods. Orlando: Grune and Stratton Inc. p 134.
  • 17. Ozturk Sarikaya, SB, Kaya, AA, Celenk Kaya, E, Senturk, M. (2015). Synthesis and determination of some biological activities of novel 2,4-dinitrophenyl derivatives. Archive der Pharmazie, Chemical Life Science, 348, 214-220
  • 18. Senturk, M, Kufrevioglu, OI, Ciftci, M. (2009). Effects of some analgesic anaesthetic drugs on human erythrocyte glutathione reductase: an in vitro study. Journal of Enzyme Inhibition and Medicinal Chemistry, 24, 420-424.
  • 19. Akkemik, E, Senturk, M, Ozgeris, FB, Taser, P, Ciftci, M. (2011). In vitro effects of some drugs on human erythrocyte glutathione reductase. Turkish Journal of Medicinal Science, 41, 235-241.
  • 20. Ekinci, D., Senturk, M. 2013. Assesment of metal inhibition of antioxidant enzyme glutathione reductase from rainbow trout liver. Journal of Enzyme Inhibition and Medicinal Chemistry. 28 (1) 11-15.
  • 21. Seefeldt, T, Zhao, Y, Chen, W, Raza, AS, Carlson, L, Herman, J, et. al. (2009). Characterization of a Novel Dithiocarbamate Glutathione Reductase Inhibitor and Its Use as a Tool to Modulate Intracellular Glutathione. Journal of Biological Chemistry, 284, 2729-2737.
  • 22. Cakmak, R, Durdagi, S, Ekinci, D, Senturk, M, Topal, G. (2011). Design, synthesis and biological evaluation of novel nitroaromatic compounds as potent glutathione reductase inhibitors. Bioorganic & Medicinal Chemistry Letters, 21, 5398-5402.
  • 23. Turella, P, Filomeni, G, Dupuis, ML, Ciriolo, MR, Molinari, A, De Maria, F, et al. (2006). A strong glutathione S-transferase inhibitor overcomes the P-glycoprotein-mediated resistance in tumor cells. 6 (7-Nitro-2,1,3-benzoxadiazol-4-ylthio) hexanol (NBDHEX) triggers a caspase-dependent apoptosis in MDR1-expressing leukemia cells. Journal of Biological Chemitry, 281, 23725-23732.
  • 24. Ascione, A, Cianfriglia, M, Dupuis, ML, Mallano, A, Sau, A, Pellizzari Tregno, F, et al. (2009). The glutathione S-transferase inhibitor 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol overcomes the MDR1-P-glycoprotein and MRP1-mediated multidrug resistance in acute myeloid leukemia cells. Cancer Chemotherapy and Pharmacology, 64, 419-425.
  • 25. Couto, N, Wood, J, Barber, J. (2016). The role of glutathione reductase and related enzymes on cellular redox homoeostasis network. Free Radical Biological Medicine. 95, 27-42.
  • 26. Benhar, M, Shytaj, IL, Stamler, JS, Savarino, A. (2016). Dual targeting of the thioredoxin and glutathione systems in cancer and HIV. Journal of Clinical Investigate, 126,1630-1639.
Year 2019, Volume: 8 Issue: 4, 438 - 443, 31.12.2019

Abstract

Project Number

ECZF.19.001

References

  • 1. Schirmer, RH, Krauth-Siegel, RL, Schulz, GE, (1989). Glutathione Reductase, John Wiley and Sons, New York, pp. 553-596.
  • 2. Kocaoglu, E, Talaz, O, Cavdar, H, Senturk, M, Supuran, CT, Ekinci, D. (2018). Determination of the inhibitory effects of N-methylpyrrole derivatives on glutathione reductase enzyme. Journal of Enzyme Inhibition and Medicinal Chemistry. 2018, 34, 51-54.
  • 3. Krauth-Siegel, RL, Bauer, H, Schirmer, RH. (2005). Dithiol proteins as guardians of the intracellular redox milieu in parasites: old and new drug targets in trypanosomes and malaria-causing plasmodia. Angewandte Chemie International Edition, 44, 690-715.
  • 4. Pastore, A, Federici, G, Bertini, E, Piemonte, F. (2003). Analysis of glutathione: implication in redox and detoxification. Clinical Chimica Acta, 333, 19-39.
  • 5. Perricone, C, De Carolis, C, Perricone, R. (2009). Glutathione: a key player in autoimmunity. Autoimmunity Reviews, 8, 697-701.
  • 6. Biot, C, Bauer, H, Schirmer, RH, Davioud-Charvet, E. (2004). 5-Substituted tetrazoles as bioisosteres of carboxylic acids. Bioisosterism and mechanistic studies on glutathione reductase inhibitors as antimalarials. Journal of Medicinal Chemistry, 47, 5972-5983.
  • 7. Grellier, P, Sarlauskas, J, Anusevicius, Z, Maroziene, A, Houee-Levin, C, Schrevel, J, et. al. (2001). Antiplasmodial activity of nitroaromatic and quinoidal compounds: Redox potential vs inhibition of erythrocyte glutathione reductase. Archives of Biochemistry and Biophysics, 393, 199-206.
  • 8. Zhao, Y, Seefeldt, T, Chen, W, Wang, X, Matthees, D, Hub,Y, et. al. (2009). Effects of glutathione reductase inhibition on cellular thiol redox state and related systems. Archives of Biochemistry and Biophysics, 485, 56-62.
  • 9. Ricci, G, De Maria, F, Antonini, G, Turella, P, Bullo, A, Stella, L, et al. (2005). 7-Nitro-2,1,3benzoxadiazole derivatives, a new class of suicide inhibitors for glutathione S-transferases. Mechanism of action of potential anticancer drugs. Journal of Biological Chemistry, 280, 26397-26405.
  • 10. Ascione, A, Cianfriglia, M, Dupuis, ML, Mallano, A, Sau, A, Pellizzari Tregno, F, et al. (2009). The glutathione S-transferase inhibitor 6-(7-nitro-2,1,3benzoxadiazol-4-ylthio)hexanol overcomes the MDR1P-glycoprotein and MRP1-mediated multidrug resistance in acute myeloid leukemia cells. Cancer Chemotherapy and Pharmacology, 64, 419-424.
  • 11. Pasello, M, Michelacci, F, Scionti, I, Hattinger, CM, Zuntini, M, Caccuri, AM, et al. (2008). Overcoming glutathione S-transferase P1-related cisplatin resistance in osteosarcoma. Cancer Research, 68, 6661-6668.
  • 12. Zhuo, R, Kosak, KM, Sankar, S, Wiles, ET, Sun, Y, Zhang, J, et al. (2014). Targeting Glutathione S-transferase M4 in Ewing sarcoma. Frontiers in Pediatrics, 83, 1-9.
  • 13. Tang, H, Yao, X, Yao, C, Zhao, X, Zuo, H, Li, Z. (2017). Anti-colon cancer effect of caffeic acid p-nitro-phenethyl ester in vitro and in vivo and detection of its metabolites. Scientific Reports, 7, 7599, 1-11.
  • 14. Noguchi, K, Uemura, H, Harada, M, Miura, T, Moriyama, M, Fukuoka, H, et al. (2001). Inhibition of PSA flare in prostate cancer patients by administration of flutamide for 2 weeks before initiation of treatment of slow-releasing LH-RH agonist. International Journal of Clinical Oncology, 6, 29-33.
  • 15. Olender, D, Żwawiak, J, Zaprutko, L. (2018). Multidirectional Efficacy of Biologically Active Nitro Compounds Included in Medicines. Pharmaceuticals, 11, 54, 1-29.
  • 16. Beutler E. (1984). Red Cell Metabolism. A manual of biochemical methods. Orlando: Grune and Stratton Inc. p 134.
  • 17. Ozturk Sarikaya, SB, Kaya, AA, Celenk Kaya, E, Senturk, M. (2015). Synthesis and determination of some biological activities of novel 2,4-dinitrophenyl derivatives. Archive der Pharmazie, Chemical Life Science, 348, 214-220
  • 18. Senturk, M, Kufrevioglu, OI, Ciftci, M. (2009). Effects of some analgesic anaesthetic drugs on human erythrocyte glutathione reductase: an in vitro study. Journal of Enzyme Inhibition and Medicinal Chemistry, 24, 420-424.
  • 19. Akkemik, E, Senturk, M, Ozgeris, FB, Taser, P, Ciftci, M. (2011). In vitro effects of some drugs on human erythrocyte glutathione reductase. Turkish Journal of Medicinal Science, 41, 235-241.
  • 20. Ekinci, D., Senturk, M. 2013. Assesment of metal inhibition of antioxidant enzyme glutathione reductase from rainbow trout liver. Journal of Enzyme Inhibition and Medicinal Chemistry. 28 (1) 11-15.
  • 21. Seefeldt, T, Zhao, Y, Chen, W, Raza, AS, Carlson, L, Herman, J, et. al. (2009). Characterization of a Novel Dithiocarbamate Glutathione Reductase Inhibitor and Its Use as a Tool to Modulate Intracellular Glutathione. Journal of Biological Chemistry, 284, 2729-2737.
  • 22. Cakmak, R, Durdagi, S, Ekinci, D, Senturk, M, Topal, G. (2011). Design, synthesis and biological evaluation of novel nitroaromatic compounds as potent glutathione reductase inhibitors. Bioorganic & Medicinal Chemistry Letters, 21, 5398-5402.
  • 23. Turella, P, Filomeni, G, Dupuis, ML, Ciriolo, MR, Molinari, A, De Maria, F, et al. (2006). A strong glutathione S-transferase inhibitor overcomes the P-glycoprotein-mediated resistance in tumor cells. 6 (7-Nitro-2,1,3-benzoxadiazol-4-ylthio) hexanol (NBDHEX) triggers a caspase-dependent apoptosis in MDR1-expressing leukemia cells. Journal of Biological Chemitry, 281, 23725-23732.
  • 24. Ascione, A, Cianfriglia, M, Dupuis, ML, Mallano, A, Sau, A, Pellizzari Tregno, F, et al. (2009). The glutathione S-transferase inhibitor 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol overcomes the MDR1-P-glycoprotein and MRP1-mediated multidrug resistance in acute myeloid leukemia cells. Cancer Chemotherapy and Pharmacology, 64, 419-425.
  • 25. Couto, N, Wood, J, Barber, J. (2016). The role of glutathione reductase and related enzymes on cellular redox homoeostasis network. Free Radical Biological Medicine. 95, 27-42.
  • 26. Benhar, M, Shytaj, IL, Stamler, JS, Savarino, A. (2016). Dual targeting of the thioredoxin and glutathione systems in cancer and HIV. Journal of Clinical Investigate, 126,1630-1639.
There are 26 citations in total.

Details

Primary Language Turkish
Journal Section Original Article
Authors

Afşin Ahmet Kaya 0000-0003-2082-6478

Murat Şentürk 0000-0002-9638-2896

Elif Çelenk Kaya 0000-0002-7811-7669

Project Number ECZF.19.001
Publication Date December 31, 2019
Published in Issue Year 2019 Volume: 8 Issue: 4

Cite

APA Kaya, A. A., Şentürk, M., & Çelenk Kaya, E. (2019). Nitro grubu İçeren Bazı Maddelerin Glutatyon Redüktaz Enzimi Üzerindeki İnhibisyon Etkisinin İncelenmesi. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi, 8(4), 438-443.
AMA Kaya AA, Şentürk M, Çelenk Kaya E. Nitro grubu İçeren Bazı Maddelerin Glutatyon Redüktaz Enzimi Üzerindeki İnhibisyon Etkisinin İncelenmesi. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi. December 2019;8(4):438-443.
Chicago Kaya, Afşin Ahmet, Murat Şentürk, and Elif Çelenk Kaya. “Nitro Grubu İçeren Bazı Maddelerin Glutatyon Redüktaz Enzimi Üzerindeki İnhibisyon Etkisinin İncelenmesi”. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi 8, no. 4 (December 2019): 438-43.
EndNote Kaya AA, Şentürk M, Çelenk Kaya E (December 1, 2019) Nitro grubu İçeren Bazı Maddelerin Glutatyon Redüktaz Enzimi Üzerindeki İnhibisyon Etkisinin İncelenmesi. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi 8 4 438–443.
IEEE A. A. Kaya, M. Şentürk, and E. Çelenk Kaya, “Nitro grubu İçeren Bazı Maddelerin Glutatyon Redüktaz Enzimi Üzerindeki İnhibisyon Etkisinin İncelenmesi”, Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi, vol. 8, no. 4, pp. 438–443, 2019.
ISNAD Kaya, Afşin Ahmet et al. “Nitro Grubu İçeren Bazı Maddelerin Glutatyon Redüktaz Enzimi Üzerindeki İnhibisyon Etkisinin İncelenmesi”. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi 8/4 (December 2019), 438-443.
JAMA Kaya AA, Şentürk M, Çelenk Kaya E. Nitro grubu İçeren Bazı Maddelerin Glutatyon Redüktaz Enzimi Üzerindeki İnhibisyon Etkisinin İncelenmesi. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi. 2019;8:438–443.
MLA Kaya, Afşin Ahmet et al. “Nitro Grubu İçeren Bazı Maddelerin Glutatyon Redüktaz Enzimi Üzerindeki İnhibisyon Etkisinin İncelenmesi”. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi, vol. 8, no. 4, 2019, pp. 438-43.
Vancouver Kaya AA, Şentürk M, Çelenk Kaya E. Nitro grubu İçeren Bazı Maddelerin Glutatyon Redüktaz Enzimi Üzerindeki İnhibisyon Etkisinin İncelenmesi. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi. 2019;8(4):438-43.