Historical and biochemical aspects of a seventeenth century gold-based aurum vitae recipe

Abstract

The medicinal chemistry and biomedical applications of gold complexes have been intensively studied over the last decades. Some complexes have been used for the treatment of rheumatoid arthritis, and a considerable number of new metallodrug candidates have been developed as new anticancer drugs and anti-infectives. However, the therapeutic use of gold and its complexes goes back to ancient times and was also of great importance for alchemists until the modern age. In this report, we give an overview of the alchemic medicine between the sixteenth and the early eighteenth century and describe the cytotoxicity and thioredoxin reductase (TrxR) inhibition of a typical “aurum vitae” medicine, which was prepared according to a recipe by Bartholomäus Kretschmar from the seventeenth century. “Aurum vitae” consists of a mixture of gold, mercury and antimony complexes and shows the expected cytotoxic and TrxR inhibitory properties providing some rationale for therapeutic effects of this kind of historical medicinal preparation.

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References

  1. 1.

    Shaw CFS (1999) Gold-based therapeutic agents. Chem Rev 99:2589–2600

    CAS  Article  Google Scholar 

  2. 2.

    Eisler R (2003) Chrysotherapy in the treatment of rheumatoid arthritis. Inflamm Res 52:487–501

    CAS  PubMed  Article  Google Scholar 

  3. 3.

    Ott I (2009) On the medicinal chemistry of gold complexes as anticancer drugs. Coord Chem Rev 253:1670–1681

    CAS  Article  Google Scholar 

  4. 4.

    Nobili S, Mini E, Landini I, Gabbiani C, Casini A, Messori L (2009) Gold compounds as anticancer agents: chemistry, cellular pharmacology and preclinical studies. Med Res Rev 30:550–580

    Google Scholar 

  5. 5.

    Berners-Price S-J, Filipovska A (2011) Gold compounds as therapeutic agents for human diseases. Metallomics 9:863–873

    Article  Google Scholar 

  6. 6.

    Navarro M (2009) Gold complexes as potential anti-parasitic agents. Coord Chem Rev 253:1619–1626

    CAS  Article  Google Scholar 

  7. 7.

    Sun RW-Y, Yu W-Y, Sun H, Che C-M (2004) In vitro inhibition of human immunodeficiency virus type-1 (HIV-1) reverse transcriptase by gold(III) porphyrins. ChemBioChem 5:1293–1298

    CAS  PubMed  Article  Google Scholar 

  8. 8.

    Simon TM, Kunishima DH, Vibert GJ, Lorber A (1981) Screening trial with the coordinated gold compound auranofin using mouse lymphocyte leukemia P388. Cancer Res. 41:94–97

    CAS  PubMed  Google Scholar 

  9. 9.

    Berners-Price SJ, Sadler PJ (1986) Gold(I) complexes with bidentate tertiary phosphine ligands: formation of annular vs. tetrahedral chelated complexes. Inorg Chem 25:3822–3827

    CAS  Article  Google Scholar 

  10. 10.

    Hunt LB (1976) The true story of purple of Cassius. Gold Bull 9:134–139

    Article  Google Scholar 

  11. 11.

    Schneider W (1972) Geschichte der pharmazeutischen Chemie. Verlag Chemie, Weinheim, pp 105–106. ISBN: 9783527252640

  12. 12.

    Stillman JM (2003) The story of alchemy and early chemistry. Dover, New York

  13. 13.

    Riecke VA (1840) Die neuern Arzneimittel, 2nd edn. Hoffmann, Stuttgart, pp 79–107

  14. 14.

    Niel JBB (1823) Recherches et observations sur les effets des preparations d’or du Dr. Chrestien dans le tratement de plusieurs maladies, Magazin für Industrie und Literatur, ed. by André-Jean Chrestien, transl. L. Cerutti, Leipzig

  15. 15.

    Tappeiner H (1919) Lehrbuch der Arzneimittellehre und Arzneiverordnungslehre, 13th edn. Vogel, Leipzig, pp 106–107

  16. 16.

    Wever E (1922) Krysolgan bei Kehlkopftuberkulose. Beiträge zur Klinik der Tuberkulose und spezifischen Tuberkulose-Forschung 53:52–56

    Article  Google Scholar 

  17. 17.

    Heisermann KF (1926) Ueber den Lupus erythematodes und seine Behandlung mit Gold. Diss, Marburg

    Google Scholar 

  18. 18.

    Dohme ARL (1921) J Am Pharm Ass 40:191–196

    Google Scholar 

  19. 19.

    Solis-Cohen S, Githen Stotesbury T (1928) Pharmacotherapeutics, materia medica and drug action. Appleton, New York/London, pp 653–656

  20. 20.

    Rubbiani R, Can S, Kitanovic I, Alborzinia H, Stefanopoulou M, Kokoschka M, Mönchensang S, Sheldrick WS, Wölfl S, Ott I (2011) Comparative in vitro evaluation of N-heterocyclic carbene gold(I) complexes of the benzimidazolylidene type. J Med Chem 54:8646–8657

    CAS  PubMed  Article  Google Scholar 

  21. 21.

    Principe LM (1998) In: Claus P, Karin F (eds) Gold, Alchemie. Lexikon einer hermetischen Wissenschaft, pp 157–160

  22. 22.

    Pagel W (1982) Paracelsus, an introduction to philosophical medicine in the era of renaissance, 2nd edn. Karger, Basel/New York, pp 101–102, 323

  23. 23.

    Klein U (2005) Technoscience avant la letter. Perspect Sci 13:227–266

    Google Scholar 

  24. 24.

    Nowotny O (2004) Die Geschichte der Goldmedizin von der Antike über die Zeit der Alchemie bis zur Gegenwart. In: Meyer K (ed) Die Schelenz-Stiftung IV 1989–2003. Wiss. Verl.-Ges., Stuttgart, pp 99–112

  25. 25.

    Figala K (1998) Quintessenz, Alchemie. In: Claus P, Karin F (eds) Lexikon einer hermetischen Wissenschaft, pp 300–302

  26. 26.

    Paracelus T (1977) De morbis amentium, Bücher und Schriften, ed. J. Huser, vol II, Hildesheim: Olms (reprint of the edition Basilea 1589)

  27. 27.

    Keil CH (1748) Compendiöses doch vollkommenes medicinisch-chymisches Handbüchlein, 6th edn. Martini, Leipzig

  28. 28.

    Paracelsus T (1971) De viribus membrorum interiorum. In: Huser J (ed) Bücher und Schriften Edition, vol I. Olms, Hildesheim (reprint of the edition Basilea 1589), part 2: 5–6

  29. 29.

    Stahl GE (1728) Materia Medica. Zimmermann und Gerlach, Dresden

  30. 30.

    Kunckel J (1716) Collegium physico-chymicum experimentale, oder Laboratorium chymicum, Heyl, Hamburg, Leipzig

  31. 31.

    Kretschmar B (1977) Vier chymische Tractätlein, VD17 39:139490P; Ferguson, Bibliotheca Chemica, vol 2, S. 509, pp 64–66. doi:10.3931/e-rara-5296

  32. 32.

    Bindoli A, Rigobello MP, Scutari G, Gabbiani C, Casini A, Messori L (2009) Thioredoxin reductase: a target for gold compounds acting as potential anticancer drugs. Coord Chem Rev 253:1692–1707

    CAS  Article  Google Scholar 

  33. 33.

    Gromer S, Arscott LD, Williams CH, Schirmer RH, Becker K (1998) Human placenta thioredoxin reductase, isolation of the selenoenzyme, steady state kinetics and inhibition by therapeutic gold compounds. J Biol Chem 273:20096–20101

    CAS  PubMed  Article  Google Scholar 

  34. 34.

    Holmgren A, Lu J (2010) Thioredoxin and thioredoxin reductase: current research with special reference to human disease. Biochem Biophys Res Commun 396:120–124

    CAS  PubMed  Article  Google Scholar 

  35. 35.

    Citta A, Schuh E, Mohr F, Folda A, Massimino ML, Bindoli A, Casini A, Rigobello MP (2013) Fluorescent silver(I) and gold(I)-N-heterocyclic carbene complexes with cytotoxic properties: mechanistic insights. Metallomics 5:1006–1015

    CAS  PubMed  Article  Google Scholar 

  36. 36.

    Sun RWY, Fong TTH, Li CKL, Yang ZF, Zou T, Siu AFM, Che CM (2013) A dinuclear cyclometalated gold(III)-phosphine complex targeting thioredoxin reductase inhibits hepatocellular carcinoma in vivo. Chem Sci 4:1979–1988

    CAS  Article  Google Scholar 

  37. 37.

    Arner ESJ, Holmgren A (2006) The thioredoxin system in cancer. Semin Cancer Biol 16:420–426

    CAS  PubMed  Article  Google Scholar 

  38. 38.

    Gandin V, Fernandes AP, Rigobello MP, Dani B, Sorrentino F, Tisato F, Björnstedt M, Bindoli A, Sturaro A, Rella R, Marzano C (2010) Cancer cell death induced by phosphine gold(I) compounds targeting thioredoxin reductase. Biochem Pharmacol 79:91–101

    Article  Google Scholar 

  39. 39.

    Hickey JL, Ruhayel RA, Barnard PJ, Baker MV, Berners-Price SJ, Filipovska A (2008) Mitochondria-targeted chemotherapeutics: the rational design of gold(I) N-heterocyclic carbene complexes that are selectively toxic to cancer cells and target protein selenols in preference to thiols. J Am Chem Soc 130:12570–12571

    CAS  PubMed  Article  Google Scholar 

  40. 40.

    Rubbiani R, Schuh E, Meyer A, Lemke J, Wimberg J, Metzler-Nolte N, Meyer F, Mohr F, Ott I (2013) TrxR inhibition and antiproliferative activities of structurally diverse gold N-heterocyclic carbene complexes. Med Chem Commun 4:942–948

    CAS  Article  Google Scholar 

  41. 41.

    Haldar AK, Sen P, Roy S (2012) Use of antimony in the treatment of leishmaniasis: current status and future directions. Mol Biol Int. doi:10.4061/2011/571242

  42. 42.

    Baiocco P, Colotti G, Franceschini S, Ilari A (2009) Molecular basis of antimony treatment in leishmaniasis. J Med Chem 52:2603–2612

    CAS  PubMed  Article  Google Scholar 

Download references

Acknowledgments

The literature research in history of pharmacy and the experimental contributions of Nuray Ates, André Morawetz, Canan Özen and Jan Carlos Quistorf are gratefully appreciated.

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Correspondence to Ingo Ott.

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Rubbiani, R., Wahrig, B. & Ott, I. Historical and biochemical aspects of a seventeenth century gold-based aurum vitae recipe. J Biol Inorg Chem 19, 961–965 (2014). https://doi.org/10.1007/s00775-014-1135-4

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Keywords

  • Alchemy
  • Antimony
  • Aurum vitae
  • Cytotoxicity
  • Gold