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In vitro and in silico Evaluation of Some Natural Molecules as Potent Glutathione Reductase Inhibitors

Year 2019, Volume: 6 Issue: 4, 310 - 316, 15.01.2020
https://doi.org/10.21448/ijsm.628043

Abstract

Glutathione
reductase inhibitors are very popular antimalarial and anticancer agents. In
this study, in vitro inhibition effects of β-sitosterol,
stigmasterol, diosgenin and jervine which containing steroidal structure were
determined against glutathione reductase enzyme. β-sitosterol, diosgenin
and jervine were isolated from Veratrum album and stigmasterol was
isolated from Artemisia dracunculus L. by chromatographic methods.
According to the results obtained, IC50 values of β-sitosterol,
stigmasterol, diosgenin and jervine were found as 1.2580, 5.2116, 0.1916 and
0.7701 µM, respectively. Among test compounds, diosgenin showed the strongest
inhibitory effect against glutathione reductase with Swissdock docking figure.
In current study first time, β-sitosterol, stigmasterol, diosgenin and
jervine were found to be much more glutathione reductase inhibitors.

Thanks

The author gratefully thanks to Swissdock for data. The author faithfully thanks to Dr. Ahmet Cakir for supportings in the structure characterization and Dr. Murat Senturk for supportings in the enzyme inhibition researchs.

References

  • [1]. Shahi, Y. Samadi, F.M., Mukherjee, S. (2019). The influence of Tumor Necrosis Factor-alpha gene polymorphism on oxidative stress in patients with oral precancerous lesions and oral cancer, Gene Rep, 17, 1-8. doi: doi.org/10.1016/j.genrep.2019.100525
  • [2]. Tsai, Y.C., Hong, C.Y., Liu, L.F., Kao C.H. (2005). Expression of ascorbate peroxidase and glutathione reductase in roots of rice seedlings in response to NaCl and H2O2, J Plant Physiol, 162, 291-299. doi: 10.1016/j.jplph.2004.06.004
  • [3]. Meister A. Anderson M.E. (1983). Glutathione, Annu Rev Biochem., 52, 711-760. doi: 10.1146/annurev.bi.52.070183.003431
  • [4]. Schirmer, R.H., Muller, J.G., Krauthsiegel, R.L., (1995). Disulfide-reductase inhibitors as chemotherapeutic - agents - the design of drugs for trypanosomiasis and malaria, Angew Chem Int Edit., 34, 141-154. doi: doi.org/10.1002/anie.199501411
  • [5]. Bohme, C.C., Arscott, L.D., Becker, K., Schirmer, R.H. (2000). Jr. Williams, C.H. 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
  • [6]. Burkard, L., Scheuermann, A., Simithy, J., Calderon, A.I. (2016). Development of a functional assay to detect inhibitors of Plasmodium falciparum glutathione reductase utilizing liquid chromatography-mass spectrometry, Biomed Chromatogr., 30, 543-547. doi: doi.org/10.1002/bmc.3580
  • [7]. Talisuna, A.O., Okello, P.E., Erhart, A., Coosemans, M., D'Alessandro, U. (2007). Intensity of malaria transmission and the spread of Plasmodium falciparum-resistant malaria: A review of epidemiologic field evidence, Am J Trop Med Hyg., 77, 170 180. WOS:000252212600027
  • [8]. Hainley, C.A., Filer, C.N. (2017). Selective D ring side chain tritiation of steroidal natural products, J Radioanal Nucl Ch., 313, 467-472. doi:10.1007/s10967-017-5322-y
  • [9]. Aydin, T., Cakir, A., Kazaz, C., Bayrak, N., Bayir, Y., Taskesenligil, Y. (2014). Insecticidal metabolites from the rhizomes of Veratrum album against adults of Colorado Potato Beetle, Leptinotarsa decemlineata, Chem Biodivers., 11, 1192-1204. doi:doi.org/10.1002/cbdv.201300407
  • [10]. Lee, S.T., Panter, K.E., Gaffield, W., Stegelmeier, B.L. (2003). Development of an enzyme-linked immunosorbent assay for the Veratrum plant teratogens: Cyclopamine and jervine, J Agr Food Chem., 51, 582-586. doi: doi.org/10.1021/jf020961s
  • [11]. Khanfar, M.A., El Sayed, K.A. (2013). The Veratrum alkaloids jervine, veratramine, and their analogues as prostate cancer migration and proliferation inhibitors: biological evaluation and pharmacophore modeling, Med Chem Res, 22, 4775-4786. doi: 10.1007/s00044-013-0495-6
  • [12]. Yamamoto M. Masui T. Sugiyama K. Yokota M. Nakagomi K. Nakazawa H. (1991). Antiinflammatory active constituents of Aloe arborescens Miller, Agr Biol Chem Tokyo, 55, 1627-1629. doi.org/10.1271/bbb1961.55.1627
  • [13]. Bouic, P.J.D., Etsebeth, S., Liebenberg, R.W., Albrecht, C.F., Pegel, K., VanJaarsveld, P.P. (1996). Beta-sitosterol and beta-sitosterol glucoside stimulate human peripheral blood lymphocyte proliferation: Implications for their use as an immunomodulatory vitamin combination, Int J Immunopharmaco., 18, 693-700. doi:doi.org/10.1016/S01920561(97)85551-8
  • [14]. Ju, Y.H., Clausen, L.M., Allred, K.F., Almada, A.L., Helferich, W.G. (2004). beta-Sitosterol, beta-sitosterol glucoside, and a mixture of beta-sitosterol and beta-sitosterol glucoside modulate the growth of estrogen-responsive breast cancer cells in vitro and in ovariectomized athymic mice, J Nutr., 134, 1145 1151. doi:doi.org/10.1093/jn/134.5.1145
  • [15]. Sethi, G., Shanmugam, M.K., Warrier, S., Merarchi, M., Arfuso, F., Kumar, A.P., Bishayee, A. (2018). Pro-apoptotic and anti-cancer properties of diosgenin: A comprehensive and critical review, Nutrients, 10, 645. doi.org/10.3390/nu10050645
  • [16]. Aydin, T., Yurtvermez, B., Senturk, M., Kazaz C., Cakir, A. (2019). Inhibitory effects of metabolites isolated from Artemisia dracunculus L. against the human carbonic anhydrase I (hCA I) and II (hCA II), Rec. Nat. Prod., 13, 216-225.doi: doi.org/10.25135/rnp.102.18.07.329
  • [17]. Kangsamaksin, T., Chaithongyot, S., Wootthichairangsan, C., Hanchaina, R., Tangshewinsirikul, C., Svasti, J. (2017). Lupeol and stigmasterol suppress tumor angiogenesis and inhibit cholangiocarcinoma growth in mice via downregulation of tumor necrosis factor-alpha, PLoS One. 12, e0189628. doi: doi.org/10.1371/journal.pone.0189628
  • [18]. Beutler, E. (1984). Red cell metabolism. A manual of biochemical methods. Grune and Stratton Inc, Orlando. ISBN: 0808916726 9780808916727
  • [19]. 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, Arch Pharm., 351, 1-8. doi: doi.org/10.1002/ardp.201800086.
  • [20]. Coban, T.A., Senturk, M., Ciftci, M., Kufrevioglu, O. I. (2007). Effects of some metal ions on human erythrocyte glutathione reductase: an in vitro study, Protein Peptide Lett., 14, 1027-1030. doi: doi.org/10.2174/092986607782541060
  • [21]. Ray, A., Chatterjee, S., Mukherjee, S., Bhattacharya, S. (2014). Arsenic trioxide induced indirect and direct inhibition of glutathione reductase leads to apoptosis in rat hepatocytes, Biometals., 27, 483-494. doi: doi 10.1007/s10534-014-9722-y
  • [22]. 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
  • [23]. Kocaoglu, E., Talaz, O., Cavdar, H., Senturk, M., Supuran, C.T., Ekinci, D. (2018). Determination of the inhibitory effects of N-methylpyrrole derivatives on glutathione reductase enzyme, J Enzym Inhib Med Chem., 34, 51-54. doi.org/10.1080/14756366.2018.1520228.
  • [24]. 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. WOS:000383578300152
  • [25]. 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: doi.org/10.1016/j.ejmech.2009.03.006
  • [26]. Chaudhary, S., Chaudhary, P.S., Chikara, S.K., Sharma, M.C., Iriti, M. (2018). Review on Fenugreek (Trigonella foenum-graecum L.) and its important secondary metabolite diosgenin, Not Bot Horti Agrobo., 46, 22-31. doi: doi.org/10.15835/nbha46110996

In vitro and in silico Evaluation of Some Natural Molecules as Potent Glutathione Reductase Inhibitors

Year 2019, Volume: 6 Issue: 4, 310 - 316, 15.01.2020
https://doi.org/10.21448/ijsm.628043

Abstract

Glutathione reductase inhibitors are very popular antimalarial and anticancer agents. In this study, in vitro inhibition effects of β-sitosterol, stigmasterol, diosgenin and jervine which containing steroidal structure were determined against glutathione reductase enzyme. β-sitosterol, diosgenin and jervine were isolated from Veratrum album and stigmasterol was isolated from Artemisia dracunculus L. by chromatographic methods. According to the results obtained, IC50 values of β-sitosterol, stigmasterol, diosgenin and jervine were found as 1.2580, 5.2116, 0.1916 and 0.7701 µM, respectively. Among test compounds, diosgenin showed the strongest inhibitory effect against glutathione reductase with Swissdock docking figure. In current study first time, β-sitosterol, stigmasterol, diosgenin and jervine were found to be much more glutathione reductase inhibitors.

References

  • [1]. Shahi, Y. Samadi, F.M., Mukherjee, S. (2019). The influence of Tumor Necrosis Factor-alpha gene polymorphism on oxidative stress in patients with oral precancerous lesions and oral cancer, Gene Rep, 17, 1-8. doi: doi.org/10.1016/j.genrep.2019.100525
  • [2]. Tsai, Y.C., Hong, C.Y., Liu, L.F., Kao C.H. (2005). Expression of ascorbate peroxidase and glutathione reductase in roots of rice seedlings in response to NaCl and H2O2, J Plant Physiol, 162, 291-299. doi: 10.1016/j.jplph.2004.06.004
  • [3]. Meister A. Anderson M.E. (1983). Glutathione, Annu Rev Biochem., 52, 711-760. doi: 10.1146/annurev.bi.52.070183.003431
  • [4]. Schirmer, R.H., Muller, J.G., Krauthsiegel, R.L., (1995). Disulfide-reductase inhibitors as chemotherapeutic - agents - the design of drugs for trypanosomiasis and malaria, Angew Chem Int Edit., 34, 141-154. doi: doi.org/10.1002/anie.199501411
  • [5]. Bohme, C.C., Arscott, L.D., Becker, K., Schirmer, R.H. (2000). Jr. Williams, C.H. 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
  • [6]. Burkard, L., Scheuermann, A., Simithy, J., Calderon, A.I. (2016). Development of a functional assay to detect inhibitors of Plasmodium falciparum glutathione reductase utilizing liquid chromatography-mass spectrometry, Biomed Chromatogr., 30, 543-547. doi: doi.org/10.1002/bmc.3580
  • [7]. Talisuna, A.O., Okello, P.E., Erhart, A., Coosemans, M., D'Alessandro, U. (2007). Intensity of malaria transmission and the spread of Plasmodium falciparum-resistant malaria: A review of epidemiologic field evidence, Am J Trop Med Hyg., 77, 170 180. WOS:000252212600027
  • [8]. Hainley, C.A., Filer, C.N. (2017). Selective D ring side chain tritiation of steroidal natural products, J Radioanal Nucl Ch., 313, 467-472. doi:10.1007/s10967-017-5322-y
  • [9]. Aydin, T., Cakir, A., Kazaz, C., Bayrak, N., Bayir, Y., Taskesenligil, Y. (2014). Insecticidal metabolites from the rhizomes of Veratrum album against adults of Colorado Potato Beetle, Leptinotarsa decemlineata, Chem Biodivers., 11, 1192-1204. doi:doi.org/10.1002/cbdv.201300407
  • [10]. Lee, S.T., Panter, K.E., Gaffield, W., Stegelmeier, B.L. (2003). Development of an enzyme-linked immunosorbent assay for the Veratrum plant teratogens: Cyclopamine and jervine, J Agr Food Chem., 51, 582-586. doi: doi.org/10.1021/jf020961s
  • [11]. Khanfar, M.A., El Sayed, K.A. (2013). The Veratrum alkaloids jervine, veratramine, and their analogues as prostate cancer migration and proliferation inhibitors: biological evaluation and pharmacophore modeling, Med Chem Res, 22, 4775-4786. doi: 10.1007/s00044-013-0495-6
  • [12]. Yamamoto M. Masui T. Sugiyama K. Yokota M. Nakagomi K. Nakazawa H. (1991). Antiinflammatory active constituents of Aloe arborescens Miller, Agr Biol Chem Tokyo, 55, 1627-1629. doi.org/10.1271/bbb1961.55.1627
  • [13]. Bouic, P.J.D., Etsebeth, S., Liebenberg, R.W., Albrecht, C.F., Pegel, K., VanJaarsveld, P.P. (1996). Beta-sitosterol and beta-sitosterol glucoside stimulate human peripheral blood lymphocyte proliferation: Implications for their use as an immunomodulatory vitamin combination, Int J Immunopharmaco., 18, 693-700. doi:doi.org/10.1016/S01920561(97)85551-8
  • [14]. Ju, Y.H., Clausen, L.M., Allred, K.F., Almada, A.L., Helferich, W.G. (2004). beta-Sitosterol, beta-sitosterol glucoside, and a mixture of beta-sitosterol and beta-sitosterol glucoside modulate the growth of estrogen-responsive breast cancer cells in vitro and in ovariectomized athymic mice, J Nutr., 134, 1145 1151. doi:doi.org/10.1093/jn/134.5.1145
  • [15]. Sethi, G., Shanmugam, M.K., Warrier, S., Merarchi, M., Arfuso, F., Kumar, A.P., Bishayee, A. (2018). Pro-apoptotic and anti-cancer properties of diosgenin: A comprehensive and critical review, Nutrients, 10, 645. doi.org/10.3390/nu10050645
  • [16]. Aydin, T., Yurtvermez, B., Senturk, M., Kazaz C., Cakir, A. (2019). Inhibitory effects of metabolites isolated from Artemisia dracunculus L. against the human carbonic anhydrase I (hCA I) and II (hCA II), Rec. Nat. Prod., 13, 216-225.doi: doi.org/10.25135/rnp.102.18.07.329
  • [17]. Kangsamaksin, T., Chaithongyot, S., Wootthichairangsan, C., Hanchaina, R., Tangshewinsirikul, C., Svasti, J. (2017). Lupeol and stigmasterol suppress tumor angiogenesis and inhibit cholangiocarcinoma growth in mice via downregulation of tumor necrosis factor-alpha, PLoS One. 12, e0189628. doi: doi.org/10.1371/journal.pone.0189628
  • [18]. Beutler, E. (1984). Red cell metabolism. A manual of biochemical methods. Grune and Stratton Inc, Orlando. ISBN: 0808916726 9780808916727
  • [19]. 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, Arch Pharm., 351, 1-8. doi: doi.org/10.1002/ardp.201800086.
  • [20]. Coban, T.A., Senturk, M., Ciftci, M., Kufrevioglu, O. I. (2007). Effects of some metal ions on human erythrocyte glutathione reductase: an in vitro study, Protein Peptide Lett., 14, 1027-1030. doi: doi.org/10.2174/092986607782541060
  • [21]. Ray, A., Chatterjee, S., Mukherjee, S., Bhattacharya, S. (2014). Arsenic trioxide induced indirect and direct inhibition of glutathione reductase leads to apoptosis in rat hepatocytes, Biometals., 27, 483-494. doi: doi 10.1007/s10534-014-9722-y
  • [22]. 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
  • [23]. Kocaoglu, E., Talaz, O., Cavdar, H., Senturk, M., Supuran, C.T., Ekinci, D. (2018). Determination of the inhibitory effects of N-methylpyrrole derivatives on glutathione reductase enzyme, J Enzym Inhib Med Chem., 34, 51-54. doi.org/10.1080/14756366.2018.1520228.
  • [24]. 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. WOS:000383578300152
  • [25]. 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: doi.org/10.1016/j.ejmech.2009.03.006
  • [26]. Chaudhary, S., Chaudhary, P.S., Chikara, S.K., Sharma, M.C., Iriti, M. (2018). Review on Fenugreek (Trigonella foenum-graecum L.) and its important secondary metabolite diosgenin, Not Bot Horti Agrobo., 46, 22-31. doi: doi.org/10.15835/nbha46110996
There are 26 citations in total.

Details

Primary Language English
Subjects Structural Biology
Journal Section Articles
Authors

Tuba Aydin 0000-0002-7653-6480

Publication Date January 15, 2020
Submission Date October 1, 2019
Published in Issue Year 2019 Volume: 6 Issue: 4

Cite

APA Aydin, T. (2020). In vitro and in silico Evaluation of Some Natural Molecules as Potent Glutathione Reductase Inhibitors. International Journal of Secondary Metabolite, 6(4), 310-316. https://doi.org/10.21448/ijsm.628043
International Journal of Secondary Metabolite

e-ISSN: 2148-6905