Investigation of Some Corticosteroids as Glutathione Reductase Inhibitor
Year 2020,
Volume: 7 Issue: 2, 119 - 125, 13.06.2020
Esra Şentürk
,
Murat Şentürk
Abstract
The detection of glutathione reductase inhibitors (GRIs) has recently become very popular due to their use as malarial and cancer drugs. Today, steroidal compounds have several clinical roles due to their potent immunomodulating and anti-inflammatory properties. In this study, GR inhibitory capacity of some corticosteroids (dexamethasone, prednisolone and methylprednisolone) has been reported. Amongst these steroidal molecules dexamethasone showed the weakest inhibitory effect on GR enzyme. IC50 values were determined by drawing % activity-[I] graphs for these corticosteroids showing inhibition effects. These corticosteroids have inhibition ranging micromolar for GR with IC50 values. These corticosteroids exhibit very potent inhibitory activity against GR enzyme at low micromolar concentrations when compared to well-known GRIs.
Supporting Institution
Ağrı İbrahim Çeçen University Research Council
Project Number
ECZF.19.001
Thanks
This work study was presented as a summary in the 3rd International Conference on Advances in Natural and Applied Sciences (ICANAS 2018), 2018, Antalya, Turkey. Authors gratefully thanks to Swissdock for in silico data.
References
- Karplus, P.A., Schulz, G.E. (1987). Refined structure of glutathione reductase at 1.54 A resolution. J. Mol. Biol., 195, 701-729. doi:https://doi.org/10.1016/0022-2836(87)9019-4
- Karplus, P.A., Pai, E.F., Schulz, G.E. (1989). A crystallographic study of the glutathione binding site of glutathione reductase at 0.3 nm resolution. Eur. J. Biochem., 178, 693-703. doi:https://doi.org/10.1111/j.1432-1033.1989.tb14500.x
- Kocaoglu, E., Talaz, O., Cavdar, H., Senturk, M., Supuran, C.T., Ekinci, D. (2019). Determination of the inhibitory effects of N-methylpyrrole derivatives on glutathione reductase enzyme. J. Enzym. Inhib. Med. Chem., 34, 51 54. doi:https://doi.org/10.1080/14756366.2018.1520228
- Yu, J., Zhou, C.Z. (2007). Crystal structure of glutathione reductase Glr1 from the yeast Saccharomyces cerevisiae. Proteins, 68, 972-979. doi:https://doi.org/10.1002/prot.21354
- Balaydin, H.T., Ozil, M., Senturk, 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. Archive der Pharm., 351, e1800086. doi:10.1002/ardp.201800086
- Couto, N., Wood, J., Barber, J. (2016). The role of glutathione reductase and related enzymes on cellular redox homoeostasis network. Free Rad. Biol. Med., 95, 27-42. doi:https://doi.org/10.1016/j.freeradbiomed.2016.02.028
- Balendiran, G.K., Dabur, R., Fraser, D. (2004). The role of glutathione in cancer. Cell Biochem. Funct., 22, 343-352. doi:10.1002/cbf.1149
- Traverso, N., Ricciarelli, R., Nitti, M., Marengo, B., Furfaro, A.L., Pronzato, M.A., Marinari, U.M., Domenicotti, C. (2013). Role of glutathione in cancer progression and chemoresistance. Oxid. Med. Cell. Longev., 2013. doi:https://doi.org/10.1155/2013/972913
- Williams, D.M. (2018). Clinical pharmacology of corticosteroids. Respir Care, 63, 655-670. doi:https://doi.org/10.4187/respcare.06314
- Stewart, P.M., Krone, N.P. (2011). The adrenal cortex. In: Melmed, S., Polonsky, K., Larsen, P.R., Kronenberg, H. eds. Williams Textbook of Endocrinology. 12th ed. Philadelphia, PA: Saunders-USA. ISBN: 9781437703245.
- Beutler, E. (1984). Red Cell Metabolism. A Manual of Biochemical Methods. Grune and Stratton Inc, Orlando. ISBN: 0808916726 9780808916727.
- Boehme, C.C., Arscott, L.D., Becker, K., Schirmer, R.H., Williams, C.H. (2000). Kinetic characterization of glutathione reductase from the malarial parasite Plasmodium falciparum comparison with the human enzyme. J. Biol. Chem., 275, 37317-37323. doi:10.1074/jbc.M007695200
- Becker, K., Rahlfs, S., Nickel, C., Schirmer, R.H. (2003). Glutathione-function and metabolism in the malarial parasite Plasmodium falciparum. Biol. Chem., 384, 551-566. doi:https://doi.org/10.1515/BC.2003.063
- Seefeldt, T., Zhao, Y., Chen, W., Raza, A.S., Carlson, L., Herman, J., Stoebner, A., Hanson, S., Foll, R., Guan, X.M. (2009). Characterization of a novel dithiocarbamate glutathione reductase inhibitor and its use as a tool to modulate intracellular glutathione. J Biol Chem., 284, 2729-2737. doi:10.1074/jbc.M802683200
- Grellier, P., Sarlauskas, J., Anusevicius, Z., Maroziene, A., Houee-Levin, C., Schrevel, J., Cenas, N. (2001). Antiplasmodial activity of nitroaromatic and quinoidal compounds: Redox potential vs inhibition of erythrocyte glutathione reductase. Arch. Biochem. Biophys., 393, 199-206. doi:https://doi.org/10.1006/abbi.2001.2487
- Senturk, M., Kufrevioglu, O.I., Ciftci, M. (2008). Effects of some antibiotics on human erythrocyte glutathione reductase: An in vitro study. J. Enzym. Inhib. Med. Chem. 23, 144-148. doi:https://doi.org/10.1080/14756360701342581
- Senturk, E., Urçar, H., Senturk, M., Yildirim, S., Gul, M., (2016). Bovine liver tissue on glutathione reductase enzyme determination of effects of thiamine, tyrosine, dopamine and adrenaline. Acta Physiol., 218, 58.
- Dalmizrak, O., Terali, K., Asuquo, E.B., Ogus, I.H., Ozer, N. (2019). The relevance of glutathione reductase ınhibition by fluoxetine to human health and disease: Insights derived from a combined kinetic and docking study. Protein J., 38, 515-524. doi:10.1007/s10930-019-09834-7
- 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. Bioorg Med Chem Lett., 21, 5398 5402. doi:https://doi.org/10.1016/j.ejmech.2009.03.006
- Couto, N., Wood, J., Barber, J. (2016). The role of glutathione reductase and related enzymes on cellular redox homoeostasis network. Free Rad. Biol. Med., 95, 27-42. doi:http://dx.doi.org/10.1016/j.freeradbiomed.2016.02.028
- Benhar, M., Shytaj, I.L., Stamler, J.S., Savarino, A. (2016). Dual targeting of the thioredoxin and glutathione systems in cancer and HIV. J. Clin. Invest., 126, 1630-1639. doi:10.1172/JCI85339
Investigation of Some Corticosteroids as Glutathione Reductase Inhibitor
Year 2020,
Volume: 7 Issue: 2, 119 - 125, 13.06.2020
Esra Şentürk
,
Murat Şentürk
Abstract
The detection of glutathione reductase inhibitors (GRIs) has recently become very popular due to their use as malarial and cancer drugs. Today, steroidal compounds have several clinical roles due to their potent immunomodulating and anti-inflammatory properties. In this study, GR inhibitory capacity of some corticosteroids (dexamethasone, prednisolone and methylprednisolone) has been reported. Amongst these steroidal molecules dexamethasone showed the weakest inhibitory effect on GR enzyme. IC50 values were determined by drawing % activity-[I] graphs for these corticosteroids showing inhibition effects. These corticosteroids have inhibition ranging micromolar for GR with IC50 values. These corticosteroids exhibit very potent inhibitory activity against GR enzyme at low micromolar concentrations when compared to well-known GRIs.
Project Number
ECZF.19.001
References
- Karplus, P.A., Schulz, G.E. (1987). Refined structure of glutathione reductase at 1.54 A resolution. J. Mol. Biol., 195, 701-729. doi:https://doi.org/10.1016/0022-2836(87)9019-4
- Karplus, P.A., Pai, E.F., Schulz, G.E. (1989). A crystallographic study of the glutathione binding site of glutathione reductase at 0.3 nm resolution. Eur. J. Biochem., 178, 693-703. doi:https://doi.org/10.1111/j.1432-1033.1989.tb14500.x
- Kocaoglu, E., Talaz, O., Cavdar, H., Senturk, M., Supuran, C.T., Ekinci, D. (2019). Determination of the inhibitory effects of N-methylpyrrole derivatives on glutathione reductase enzyme. J. Enzym. Inhib. Med. Chem., 34, 51 54. doi:https://doi.org/10.1080/14756366.2018.1520228
- Yu, J., Zhou, C.Z. (2007). Crystal structure of glutathione reductase Glr1 from the yeast Saccharomyces cerevisiae. Proteins, 68, 972-979. doi:https://doi.org/10.1002/prot.21354
- Balaydin, H.T., Ozil, M., Senturk, 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. Archive der Pharm., 351, e1800086. doi:10.1002/ardp.201800086
- Couto, N., Wood, J., Barber, J. (2016). The role of glutathione reductase and related enzymes on cellular redox homoeostasis network. Free Rad. Biol. Med., 95, 27-42. doi:https://doi.org/10.1016/j.freeradbiomed.2016.02.028
- Balendiran, G.K., Dabur, R., Fraser, D. (2004). The role of glutathione in cancer. Cell Biochem. Funct., 22, 343-352. doi:10.1002/cbf.1149
- Traverso, N., Ricciarelli, R., Nitti, M., Marengo, B., Furfaro, A.L., Pronzato, M.A., Marinari, U.M., Domenicotti, C. (2013). Role of glutathione in cancer progression and chemoresistance. Oxid. Med. Cell. Longev., 2013. doi:https://doi.org/10.1155/2013/972913
- Williams, D.M. (2018). Clinical pharmacology of corticosteroids. Respir Care, 63, 655-670. doi:https://doi.org/10.4187/respcare.06314
- Stewart, P.M., Krone, N.P. (2011). The adrenal cortex. In: Melmed, S., Polonsky, K., Larsen, P.R., Kronenberg, H. eds. Williams Textbook of Endocrinology. 12th ed. Philadelphia, PA: Saunders-USA. ISBN: 9781437703245.
- Beutler, E. (1984). Red Cell Metabolism. A Manual of Biochemical Methods. Grune and Stratton Inc, Orlando. ISBN: 0808916726 9780808916727.
- Boehme, C.C., Arscott, L.D., Becker, K., Schirmer, R.H., Williams, C.H. (2000). Kinetic characterization of glutathione reductase from the malarial parasite Plasmodium falciparum comparison with the human enzyme. J. Biol. Chem., 275, 37317-37323. doi:10.1074/jbc.M007695200
- Becker, K., Rahlfs, S., Nickel, C., Schirmer, R.H. (2003). Glutathione-function and metabolism in the malarial parasite Plasmodium falciparum. Biol. Chem., 384, 551-566. doi:https://doi.org/10.1515/BC.2003.063
- Seefeldt, T., Zhao, Y., Chen, W., Raza, A.S., Carlson, L., Herman, J., Stoebner, A., Hanson, S., Foll, R., Guan, X.M. (2009). Characterization of a novel dithiocarbamate glutathione reductase inhibitor and its use as a tool to modulate intracellular glutathione. J Biol Chem., 284, 2729-2737. doi:10.1074/jbc.M802683200
- Grellier, P., Sarlauskas, J., Anusevicius, Z., Maroziene, A., Houee-Levin, C., Schrevel, J., Cenas, N. (2001). Antiplasmodial activity of nitroaromatic and quinoidal compounds: Redox potential vs inhibition of erythrocyte glutathione reductase. Arch. Biochem. Biophys., 393, 199-206. doi:https://doi.org/10.1006/abbi.2001.2487
- Senturk, M., Kufrevioglu, O.I., Ciftci, M. (2008). Effects of some antibiotics on human erythrocyte glutathione reductase: An in vitro study. J. Enzym. Inhib. Med. Chem. 23, 144-148. doi:https://doi.org/10.1080/14756360701342581
- Senturk, E., Urçar, H., Senturk, M., Yildirim, S., Gul, M., (2016). Bovine liver tissue on glutathione reductase enzyme determination of effects of thiamine, tyrosine, dopamine and adrenaline. Acta Physiol., 218, 58.
- Dalmizrak, O., Terali, K., Asuquo, E.B., Ogus, I.H., Ozer, N. (2019). The relevance of glutathione reductase ınhibition by fluoxetine to human health and disease: Insights derived from a combined kinetic and docking study. Protein J., 38, 515-524. doi:10.1007/s10930-019-09834-7
- 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. Bioorg Med Chem Lett., 21, 5398 5402. doi:https://doi.org/10.1016/j.ejmech.2009.03.006
- Couto, N., Wood, J., Barber, J. (2016). The role of glutathione reductase and related enzymes on cellular redox homoeostasis network. Free Rad. Biol. Med., 95, 27-42. doi:http://dx.doi.org/10.1016/j.freeradbiomed.2016.02.028
- Benhar, M., Shytaj, I.L., Stamler, J.S., Savarino, A. (2016). Dual targeting of the thioredoxin and glutathione systems in cancer and HIV. J. Clin. Invest., 126, 1630-1639. doi:10.1172/JCI85339