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Abstract

Cystathionine-g-lyase (CSE) 1-(1H-tetrazol-5-yl) but-3-yn-1-amine) is co-enzyme play an important role in in situ production of H2S. In this study, herein reported the synthesis of a new molecule, which is inhibitors of CSE. Hydrogen sulfide is a signaling molecule in the form of gas, also it modulates a large number of mammalian physiological processes. Cystathionine-g-lyase (CSE) catalyzes hydrogen sulfide synthesis and is a target for modulating under pathophysiological conditions. CSE is inhibited by propargylglycine (PPG), thus this study disclosed that it is useful for CSE inhibitors in the treatment of diseases where CSE inhibition provides therapeutic advantage to the patient having the disease.

Keywords

Cystathionine-g-lyase Hydrogen sulfide Propargylglycine.

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Sukhwal, P., Pathan, S., Singh Chundawat, N., Bhargav, A., Anil Vithal, R., & Pal Singh, G. (2022). Synthesis and Characterization of Cystathionine-g-lyase (CSE) Inhibitors 1-(1H-Tetrazol-5-yl)but-3-yn-1-amine. Asian Journal of Organic & Medicinal Chemistry, 7(2), 159–162. https://doi.org/10.14233/ajomc.2022.AJOMC-P379
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References

  1. M.N. Hughes, M.N. Centelles and K.P. Moore, Making and Working with Hydrogen Sulfide: The Chemistry and Generation of Hydrogen Sulfide in vitro and its Measurement in vivo: A Review, Free Radic. Biol. Med., 47, 1346 (2009); https://doi.org/10.1016/j.freeradbiomed.2009.09.018
  2. E. Lowicka and J. Beltowski, Hydrogen Sulfide (H2S) - The Third Gas of Interest for Pharmacologists, Pharmacol. Rep., 59, 4 (2007).
  3. P. Kamoun, Endogenous Production of Hydrogen Sulfide in Mammals, Amino Acids, 26, 243 (2004); https://doi.org/10.1007/s00726-004-0072-x
  4. L. Bao, C. Vlcek, V. Paces and J.P. Kraus, Identification and Tissue Distribution of Human Cystathionine b-Synthase mRNA Isoforms, Arch. Biochem. Biophys., 350, 95 (1998); https://doi.org/10.1006/abbi.1997.0486
  5. W. Guo, J.-T. Kan, Z.-Y. Cheng, J.-F. Chen, Y.-Q. Shen, J. Xu, D. Wu and Y.-Z. Zhu, Oxid. Med. Cellul. Long., 2012, 878052 (2012); https://doi.org/10.1155/2012/878052
  6. M.R. Filipovic, J. Zivanovic, B. Alvarez and R. Banerjee, Chemical Biology of H2S Signaling through Persulfidation, Chem. Rev., 118, 1253 (2018); https://doi.org/10.1021/acs.chemrev.7b00205
  7. O. Kabil and R. Banerjee, Redox Biochemistry of Hydrogen Sulfide, J. Biol. Chem., 285, 21903 (2010); https://doi.org/10.1074/jbc.R110.128363
  8. S. Singh and R. Banerjee, PLP-Dependent H2S Biogenesis, Biochim. Biophys. Acta, 1814, 1518 (2011); https://doi.org/10.1016/j.bbapap.2011.02.004
  9. P.K. Yadav, K. Yamada, T. Chiku, M. Koutmos and R. Banerjee, Structure and Kinetic Analysis of H2S Production by Human Mercaptopyruvate Sulfurtransferase, J. Biol. Chem., 288, 20002 (2013); https://doi.org/10.1074/jbc.M113.466177
  10. N. Nagahara, T. Yoshii, Y. Abe and T. Matsumura, Thioredoxin-dependent Enzymatic Activation of Mercaptopyruvate Sulfurtransferase, J. Biol. Chem., 282, 1561 (2007); https://doi.org/10.1074/jbc.M605931200
  11. E. Mosharov, M.R. Cranford and R. Banerjee, The Quantitatively Important Relationship between Homocysteine Metabolism and Glutathione Synthesis by the Transsulfuration Pathway and Its Regulation by Redox Changes, Biochemistry, 39, 13005 (2000); https://doi.org/10.1021/bi001088w
  12. V. Vitvitsky, M. Thomas, A. Ghorpade, H.E. Gendelman and R. Banerjee, A Functional Transsulfuration Pathway in the Brain Links to Glutathione Homeostasis, J. Biol. Chem., 281, 35785 (2006); https://doi.org/10.1074/jbc.M602799200
  13. R. Banerjee, Catalytic Promiscuity and Heme-Dependent Redox Regulation of H2S Synthesis, Curr. Opin. Chem. Biol., 37, 115 (2017); https://doi.org/10.1016/j.cbpa.2017.02.021
  14. T. Chiku, D. Padovani, W. Zhu, S. Singh, V. Vitvitsky and R. Banerjee, H2S Biogenesis by Human Cystathionine g-Lyase Leads to the Novel Sulfur Metabolites Lanthionine and Homolanthionine and is Responsive to the Grade of Hyperhomocysteinemia, J. Biol. Chem., 284, 11601 (2009); https://doi.org/10.1074/jbc.M808026200
  15. S. Singh, D. Padovani, R.A. Leslie, T. Chiku and R. Banerjee, Relative Contributions of Cystathionine b-Synthase and g-Cystathionase to H2S Biogenesis via Alternative Trans-sulfuration Reactions, J. Biol. Chem., 284, 22457 (2009); https://doi.org/10.1074/jbc.M109.010868
  16. S. Taoka, S. Ohja, X. Shan, W.D. Kruger and R. Banerjee, Evidence for Heme-mediated Redox Regulation of Human Cystathionine b-Synthase Activity, J. Biol. Chem., 273, 25179 (1998); https://doi.org/10.1074/jbc.273.39.25179
  17. S. Taoka and R. Banerjee, Characterization of NO Binding to Human Cystathionine b-Synthase: Possible implications of the Effects of CO and NO Binding to the Human Enzyme, J. Inorg. Biochem., 87, 245 (2001); https://doi.org/10.1016/S0162-0134(01)00335-X
  18. S. Taoka, M. West and R. Banerjee, Characterization of the Heme and Pyridoxal Phosphate Cofactors of Human Cystathionine b-Synthase Reveals Nonequivalent Active Sites, Biochemistry, 38, 2738 (1999); https://doi.org/10.1021/bi9826052
  19. O. Kabil, V. Yadav and R. Banerjee, J. Biol. Chem., 291, 16418 (2016); https://doi.org/10.1074/jbc.C116.742213
  20. O. Kabil, V. Vitvitsky, P. Xie and R. Banerjee, The Quantitative Significance of the Transsulfuration Enzymes for H2S Production in Murine Tissues, Antioxid. Redox Signal., 15, 363 (2011); https://doi.org/10.1089/ars.2010.3781
  21. J.N. Jansonius, Structure, Evolution and Action of Vitamin B6-Dependent Enzymes, Curr. Opin. Struct. Biol., 8, 759 (1998); https://doi.org/10.1016/S0959-440X(98)80096-1
  22. J. Wang and R. Hegele, Genomic Basis of Cystathioninuria (MIM 219500) Revealed by Multiple Mutations in Cystathionine Gamma-Lyase (CTH), Hum. Genet., 112, 404 (2003); https://doi.org/10.1007/s00439-003-0906-8
  23. Q. Sun, R. Collins, S. Huang, L. Holmberg-Schiavone, G.S. Anand, C.H. Tan, S. van-den-Berg, L.W. Deng, P.K. Moore, T. Karlberg and J. Sivaraman, Structural Basis for the Inhibition Mechanism of Human Cystathionine g-Lyase, an Enzyme Responsible for the Production of H2S, J. Biol. Chem., 284, 3076 (2009); https://doi.org/10.1074/jbc.M805459200
  24. S. Yamagata, T. Yasugahira, Y. Okuda and T. Iwama, Conversion of the Aminocrotonate Intermediate Limits the Rate of g-Elimination Reaction Catalyzed by L-Cystathionine g-Lyase of the Yeast Saccharomyces cerevisiae, J. Biochem., 134, 607 (2003); https://doi.org/10.1093/jb/mvg179
  25. T. Ida, T. Sawa, H. Ihara, Y. Tsuchiya, Y. Watanabe, Y. Kumagai, M. Suematsu, H. Motohashi, S. Fujii, T. Matsunaga, M. Yamamoto, K. Ono, N.O. Devarie-Baez, M. Xian, J.M. Fukuto and T. Akaike, Reactive Cysteine Persulfides and S-Polythiolation Regulate Oxidative Stress and Redox Signaling, Proc. Natl. Acad. Sci. USA, 111, 7606 (2014); https://doi.org/10.1073/pnas.1321232111
  26. C. Szabo and A. Papapetropoulos, International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H2S Levels: H2S Donors and H2S Biosynthesis Inhibitors, Pharmacol. Rev., 69, 497 (2017); https://doi.org/10.1124/pr.117.014050
  27. S.G. Duron, J. Chapman, S.G. Sydserff, S.G. Rao and G. Srinivas, Cystathionine-g-gamma-lyase (CSE) Inhibitors, WO/2014/018569 (2014).
  28. S.G. Duron, J. Chapman, S.G. Sydserff, S.G. Rao and G. Srinivas, Cystathionine-g-lyase (CSE) Inhibitors, WO2014/018570 (2014).
  29. G. Stein, S.G. Rao, S.G. Duron, J. Chapman and S.G. Sydserff, Use of CSE Inhibitors for the Treatment of Cutaneous Injuries or Conditions and Sleep-Related Breathing Disorders, WO2014/018571 (2014).