Skip to main content
SpringerLink
Log in

Electrochemical Potential-Biological Activity Relationships of Cyclic Sulfur-Containing Molecules Against Steinernema feltiae, Botrytis cinerea, and Neuro 2a Cell Line

  • Redox Modulators (C Jacob, Section Editor)
  • Published:
Current Pharmacology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

This article provides a brief overview of electrochemical potential-biological activity relationships of natural and synthetic cyclic sulfur-containing molecules against Steinernema feltiae, Botrytis cinerea, and Neuro 2a cell line (from murine neuroblastoma).

Recent Findings

This article finds natural cyclic sulfur-containing molecules and their synthetic analogues were more reducing than glutathione (GSH) and therefore apparently did not react with GSH. The nematicidal assay indicated that cyclic disulfide compound of 1 (3-vinyl-4H-1,2-dithiin, 1,2-VDT) was more active against Steinernema feltiae with the LD50 value 151.93 ± 1.3 μM, while dithiole thione group compounds showed moderate activity against this nematode. The article also finds compound 7 (3H-1,2-dithiole-3-thione or dithiolethione, DT) has a strong activity against all different strains of Botrytis cinerea in the range concentration of 0.1–0.5 mM. This article also finds that compounds 3 (1,2-dithiane, 1,2-DT), 4 (1,5-dithiacyclooctane, 1,5-DTCO), and 7 (3H-1,2-dithiole-3-thione or dithiolethione, DT) possess some moderate activity on Neuro 2a cell lines.

Summary

Antinematode, antifungal, and anticancer activity of cyclic sulfur-containing molecules indicated that they could be promising candidates for “green pesticides” or phytoprotectans and for cancer prevention.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Schafer FQ, Buettner GR. Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radical Bio Med. 2001;30:1191–212.

    Article  CAS  Google Scholar 

  2. Jacob C, Giles GL, Giles NM, Sies H. Sulfur and selenium: the role of oxidation state in protein structure and function. Angew Chem Int Ed. 2003;42:4742–58.

    Article  CAS  Google Scholar 

  3. Giles GI, Tasker KM, Jacob C. Hypothesis: the role of reactive sulfur species in oxidative stress. Free Radical Bio Med. 2001;31:1279–83.

    Article  CAS  Google Scholar 

  4. Doering M. Development of multifunctional agents and their biological evaluation in the context of cancer and inflammatory diseases. Department of Bioorganic Chemistry. School of Pharmacy. Universitaet des Saarlandes. Dissertation. 2012.

  5. Halliwell B. Oxidative stress and cancer: have we moved forward? Biochem J. 2007;401:1–11.

    Article  CAS  PubMed  Google Scholar 

  6. Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 2007;39:44–84.

    Article  CAS  Google Scholar 

  7. Gems D, Partridge L. Stress-response hormesis and aging: “that which does not kill us makes us stronger”. Cell Metab. 2008;7:200–3.

    Article  CAS  PubMed  Google Scholar 

  8. Czepukojc B, Viswanathan UM, Raza A, Ali S, Burkholz T, Jacob C. Tetrasulfanes as selective modulators of the cellular thiolstat. Phosphorus Sulfur. 2013;188:446–53.

    Article  CAS  Google Scholar 

  9. Jacob C, Battaglia E, Burkholz T, Peng D, Bagrel D, Montenarh M. Control of oxidative posttranslational cysteine modifications: from intricate chemistry to widespread biological and medical applications. Chem Res Toxicol. 2012;25:588–604.

    Article  CAS  PubMed  Google Scholar 

  10. Jacob C, Ba LA. Open season for hunting and trapping post-translational cysteine modifications in proteins and enzymes. Chembiochem. 2011;12(6):841–4.

    Article  CAS  PubMed  Google Scholar 

  11. •• Jacob C. Redox signalling via the cellular thiolstat. Biochem Soc Trans. 2011;39:1247–53. This paper summarizes ‘thiolstat’ is provided by the complex redox chemistry of the amino acid cysteine, able to participate in different redox processes.

  12. Weber ND, Andersen DO, North JA, Murray BK, Lawson LD, Hughes BG. In vitro virucidal effects of Allium sativum (garlic) extract and compounds. Planta Med. 1992;58:417–23.

    Article  CAS  PubMed  Google Scholar 

  13. Block E. Garlic and other alliums—the lore and the science. Cambridge: Royal Society of Chemistry; 2010.

    Google Scholar 

  14. Shams-Ghahfarokhi M, Shokoohamiri MR, Amirrajab N, Moghadasi B, Ghajari A, Zeini F, et al. In vitro antifungal activities of Allium cepa, Allium sativum and ketoconazole against some pathogenic yeasts and dermatophytes. Fitoterapia. 2006;77:321–3.

    Article  PubMed  Google Scholar 

  15. • Jacob C. A scent of therapy: pharmacological implications of natural products containing redox-active sulfur atoms. Nat Prod Rep. 2006;23:851–63. This paper summarizes that sulfur-containing molecules allow reactive sulfur species (RSS) to interact with oxidative stressors, to affect the function of redox-sensitive cysteine proteins and to disrupt the integrity of DNA and cellular membranes.

  16. Block E, Ahmad S, Catalfamo JL, Jain MK, Apitzcastro R. Antithrombotic organosulfur compounds from garlic - structural, mechanistic, and synthetic studies. J Am Chem Soc. 1986;108:7045–55.

    Article  CAS  Google Scholar 

  17. Okada Y, Tanaka K, Fujita I, Sato E, Okajima H. Antioxidant activity of thiosulfinates derived from garlic. Redox Rep. 2005;10:96–102.

    Article  CAS  PubMed  Google Scholar 

  18. Egenschwind C, Eckard R, Jekat FW, Winterhoff H. Pharmacokinetics of Vinyldithiins, Transformation products of allicin. Planta Med. 1992;58:8–13.

    Article  CAS  Google Scholar 

  19. Zhou S-F. Supportive cancer care with Chinese medicine. Netherlands: Springer; 2010.

    Google Scholar 

  20. Beslin P. A facile synthesis of 2 thioacrolein dimers - a new entry to a flavor component in asparagus. J Heterocyclic Chem. 1983;20:1753–4.

    Article  CAS  Google Scholar 

  21. Manabe T, Hasumi A, Sugiyama M, Yamazaki M, Saito K. Alliinase [S-alk(en)yl-L-cysteine sulfoxide lyase] from Allium tuberosum (Chinese chive) - purification, localization, cDNA cloning and heterologous functional expression. Eur J Biochem. 1998;257:21–30.

    Article  CAS  PubMed  Google Scholar 

  22. Flora SJ. Structural, chemical and biological aspects of antioxidants for strategies against metal and metalloid exposure. Oxidative Med Cell Longev. 2009;2:191–206.

    Article  Google Scholar 

  23. Sendl A, Schliack M, Loser R, Stanislaus F, Wagner H. Inhibition of cholesterol-synthesis in vitro by extracts and isolated compounds prepared from garlic and wild garlic. Atherosclerosis. 1992;94:79–85.

    Article  CAS  PubMed  Google Scholar 

  24. Sheu CM, Foote CS, Gu CL. Photooxidation of 1,5-dithiacyclooctane - a novel C-S bond-cleavage. J Am Chem Soc. 1992;114:3015–21.

    Article  CAS  Google Scholar 

  25. Tazzari V, Cappelletti G, Casagrande M, Perrino E, Renzi L, Del Soldato P, et al. New aryldithiolethione derivatives as potent histone deacetylase inhibitors. Bioorg Med Chem. 2010;18:4187–94.

    Article  CAS  PubMed  Google Scholar 

  26. Curphey TJ. Thionation with the reagent combination of phosphorus pentasulfide and hexamethyldisiloxane. J Organomet Chem. 2002;67:6461–73.

    Article  CAS  Google Scholar 

  27. Munday R, Zhang Y, Paonessa JD, Munday CM, Wilkins AL, Babu J. Synthesis, biological evaluation, and structure-activity relationships of dithiolethiones as inducers of cytoprotective phase 2 enzymes. J Med Chem. 2010;53:4761–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Munday R, Munday CM. Induction of phase II enzymes by 3H-1,2-dithiole-3-thione: dose-response study in rats. Carcinogenesis. 2004;25(9):1721–5.

    Article  CAS  PubMed  Google Scholar 

  29. Hamann CH, Vielstich W. Elektrochemie. Weinheim: Wiley VCH Verlag GmbH; 2005.

    Google Scholar 

  30. Bard AJ, Faulkner LR. Electrochemical methods: fundamentals and applications. 2nd ed. New York: A John Wiley & Sons; 2001.

    Google Scholar 

  31. Brett CMA, Oliveira Brett AM. Electrochemistry, Principles, methods, and applications. Oxford: Oxford Science Publications; 1993.

    Google Scholar 

  32. Hamann CH, Vielstich W. Chemie Ingenieur Technik. Weinheim: Wiley VCH Verlag GmbH; 1999.

    Google Scholar 

  33. Kissinger PT, Heineman WR. Cyclic voltammetry. J Chem Educ. 1983;60:702–6.

    Article  CAS  Google Scholar 

  34. Stenken JA, Puckett DL, Lunte SM, Lunte CE. Detection of N-acetylcysteine, cysteine and their disulfides in urine by liquid chromatography with a dualelectrode amperometric detector. J Pharm Biomed Anal. 1990;8:85–9.

    Article  CAS  PubMed  Google Scholar 

  35. Adam V, Fabrik I, Kohoutkova V, et al. Automated electrochemical analyzer as a new tool for detection of thiols. Int J Electrochem Sci. 2010;5:429–47.

    CAS  Google Scholar 

  36. Ralph TR, Hitchman ML, Millington JP, Walsh FC. The electrochemistry of L-cystine and L-cysteine.1. Thermodynamic and kinetic-studies. J Electroanal Chem. 1994;375:1–15.

    Article  CAS  Google Scholar 

  37. • Jacob C, Special issue: redox active natural products and their interaction with cellular signalling pathways. Molecules. 2014;19:19588–93. This paper summarizes that redox active compounds, especially of reactive sulfur species (RSS) is a powerful platform to "intracellular diagnostics" in different organisms.

  38. •• Domínguez Álvarez E, Viswanathan UM, Burkholz T, Khairan K, Jacob C. Bio-Electrochemistry and Chalcogens. Chapter 7 in M. Schlesinger (ed.). Applications of Electrochemistry in Medicine. Modern Aspects of Electrochemistry. 2013; 56:249-282. This paper summarizes that redox active compounds, especially of reactive sulfur species (RSS) is a powerful platform to "intracellular diagnostics" in different organisms.

  39. • Burkholz T. Oxidative stress and electrochemical procedure for surface decontamination in dialyses. Department of Bioorganic Chemistry. School of Pharmacy. Universitaet des Saarlandes. Dissertation. 2010. This paper summarizes that cyclic voltammetry is able to monitor (bio-) chemical process or redox processes at the cellular level.

  40. Sarakbi MB. Natural Products and related compounds as promising antioxidants and antimicrobial agents. Department of Bioorganic Chemistry. School of Pharmacy. Universitaet des Saarlandes. Diplom. 2009.

  41. Clennan EL, Liao C. The hydroperoxysulfonium ylide. An aberration or a ubiquitous intermediate? Tetrahedron. 2006;62:10724–8.

    Article  CAS  Google Scholar 

  42. Buecher EJ, Popiel I. Liquid culture of the entomogenous nematode Steinernema feltiae with its bacterial symbiont. J Nematol. 1989;21:500–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Collado IG, Sanchez AJ, Hanson JR. Fungal terpene metabolites: biosynthetic relationships and the control of the phytopathogenic fungus Botrytis cinerea. Nat Prod Rep. 2007;24:674–86.

    Article  CAS  PubMed  Google Scholar 

  44. Calderon FH, Bonnefont A, Munoz FJ, Fernandez V, Videla LA, Inestrosa NC. PC12 and neuro 2a cells have different susceptibilities to acetylcholinesterase-amyloid complexes, amyloid 25-35 fragment, glutamate, and hydrogen peroxide. J Neurosci Res. 1999;56:620–31.

    Article  CAS  PubMed  Google Scholar 

  45. Kaneshiro ES, Wyder MA, Wu YP, Cushion MT. Reliability of calcein acetoxy methyl-ester and ethidium homodimer or propidium iodide for viability assessment of microbes. J Microbiol Methods. 1993;17:1–16.

    Article  CAS  Google Scholar 

  46. Whittemore ER, Loo DT, Watt JA, Cotman CW. A detailed analysis of hydrogen peroxide-induced cell death in primary neuronal culture. Neuroscience. 1995;67:921–32.

    Article  CAS  PubMed  Google Scholar 

  47. Whittemore ER, Loo DT, Cotman CW. Exposure to hydrogen peroxide induces cell death via apoptosis in cultured rat cortical neurons. Neuroreport. 1994;5:1485–8.

    Article  CAS  PubMed  Google Scholar 

  48. Schneider T, Muthukumar Y, Hinkelmann B, Franke R, Doring M, Jacob C, et al. Deciphering intracellular targets of organochalcogen based redox catalysts. Medchemcomm. 2012;3:784–7.

    Article  CAS  Google Scholar 

  49. Doering M, Diesel B, Gruhlke MCH, Viswanathan UM, Manikova D, Chovanec M, et al. Selenium- and tellurium-containing redox modulators with distinct activity against macrophages: possible implications for the treatment of inflammatory diseases. Tetrahedron. 2012;68:10577–85.

    Article  CAS  Google Scholar 

  50. Spencer JPE, Jenner A, Aruoma OI, Evans PJ, Kaur H, Dexter DT, et al. Intense oxidative DNA-damage promoted by L-dopa and its metabolites implications for neurodegenerative disease. FEBS Lett. 1994;353:246–50.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacy, Universitas Syiah Kuala, Darussalam, Banda Aceh, Indonesia

    Khairan Khairan

  2. Herbal Medicinal Research Centre, Universitas Syiah Kuala, Darussalam, Banda Aceh, Indonesia

    Khairan Khairan

  3. Laboratoire d’Ingénierie Moléculaire et Biochimie Pharmacologique, Institut Jean Barriol, Université Paul Verlaine-Metz, 1 Boulevard Arago, 57070, Metz, France

    Lalla Aïcha Ba

  4. Department of Applied Materials Engineering, Institute of Air Handling and Refrigeration (ILK), Dresden, Germany

    Torsten Burkholz

  5. Department of Biology, University of Kaiserslautern, Kaiserslautern, Germany

    Michaela Leroch & Matthias Hahn

  6. Department of Microsystems Technique, University of Applied Sciences, FH-Kaiserslautern, Standort-Zweibruecken, Germany

    Tanya Schwab, Markus Klotz & Karl-Herbert Schaefer

  7. School of Pharmacy, Universitaet des Saarlandes, Saarbruecken, Germany

    Claus Jacob

Authors
  1. Khairan Khairan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lalla Aïcha Ba
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Torsten Burkholz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michaela Leroch
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Matthias Hahn
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tanya Schwab
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Markus Klotz
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Karl-Herbert Schaefer
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Claus Jacob
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Khairan Khairan.

Ethics declarations

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Open Access

This article is distributed under the terms of the Creative Commons Attribution 4.0 International Lisence (http://creativecommons.org/licences /by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons lisences, and indicate if changes were made.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Redox Modulators

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Khairan, K., Ba, L.A., Burkholz, T. et al. Electrochemical Potential-Biological Activity Relationships of Cyclic Sulfur-Containing Molecules Against Steinernema feltiae, Botrytis cinerea, and Neuro 2a Cell Line. Curr Pharmacol Rep 5, 174–187 (2019). https://doi.org/10.1007/s40495-019-00179-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40495-019-00179-4

Keywords

Search

Navigation