Wege zu neuen Medikamenten gegen Infektionskrankheiten

  • Markus FischerEmail author
  • Adelbert Bacher


Die menschliche Lebenserwartung hat sich innerhalb eines relativ kurzen Zeitraums von etwa 100 Jahren nahezu verdoppelt. Ein wesentlicher Faktor war die Verhütung und Behandlung von Infektionskrankheiten durch Impfungen und hochwirksame Medikamente (Antibiotika, Antimykotika, Viruzide). Durch den erfolgreichen Einsatz der Antiinfektiva werden jedoch resistente Erregerformen selektioniert. Deshalb können wir uns bei der Behandlung und Verhütung von Infektionskrankheiten nicht mit dem Erreichten zufrieden geben. Erforderlich wäre vielmehr die fortlaufende Entwicklung neuer Medikamente als Ersatz für Substanzen, die auf Grund der Erregerresistenz nicht mehr für den Einsatz geeignet sind.


The human lifespan has been almost doubled over the last century. One of the reasons was the prevention and cure of infectious diseases by vaccination and therapy with highly efficient antibiotics. Unfortunately, the medical application of antibiotics is conducive to the selection of drug‐resistant pathogens. Hence, the therapeutic agents need to be progressively replaced by novel drugs in order to cope with the problem of pathogen resistance.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Arias, C.A. and B.E. Murray, Antibiotic–resistant bugs in the 21st century––a clinical super–challenge. N Engl J Med, 2009. 360(5): p. 439–43.PubMedCrossRefGoogle Scholar
  2. 2.
    Woodford, N. and D.W. Wareham, Tackling antibiotic resistance: a dose of common antisense? J Antimicrob Chemother, 2009. 63(2): p. 225–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Walsh, C. and G. Wright, Introduction: antibiotic resistance. Chem Rev, 2005. 105(2): p. 391–4.PubMedCrossRefGoogle Scholar
  4. 4.
    Neu, H.C., The crisis in antibiotic resistance. Science, 1992. 257(5073): p. 1064–73.PubMedCrossRefGoogle Scholar
  5. 5.
    Neu, H.C., et al., Antibiotic resistance. Epidemiology and therapeutics. Diagn Microbiol Infect Dis, 1992. 15(2 Suppl): p. 53S–60S.PubMedGoogle Scholar
  6. 6.
    Boucher, H.W., et al., Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin Infect Dis, 2009. 48(1): p. 1–12.PubMedCrossRefGoogle Scholar
  7. 7.
    Pendleton, J.N., S.P. Gorman, and B.F. Gilmore, Clinical relevance of the ESKAPE pathogens. Expert Rev Anti Infect Ther, 2013. 11(3): p. 297–308.PubMedCrossRefGoogle Scholar
  8. 8.
    Schlitzer, M., Malaria: Lebensrettende Prophylaxe und Therapie. Pharmazeutische Zeitung, 2010(12).Google Scholar
  9. 9.
    Hobhouse, H., Sechs Pflanzen verändern die Welt. Chinarinde, Zuckerrohr, Tee, Baumwolle, Kartoffel, Kokastrauch. 2001: Klett– Cotta.Google Scholar
  10. 10.
    Fleming, A., On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenzæ. Br J Exp Pathol, 1929. 10(3): p. 226–36.Google Scholar
  11. 11.
    Abraham, E.P., et al., Further observations on penicillin. 1941. Eur J Clin Pharmacol, 1992. 42(1): p. 3–9.PubMedGoogle Scholar
  12. 12.
    Chain, E., et al., Penicillin as a chemotherapeutic agent. 1940. Clin Orthop Relat Res, 1993(295): p. 3–7.PubMedGoogle Scholar
  13. 13.
    Douglas, N.M., et al., Artemisinin combination therapy for vivax malaria. Lancet Infect Dis, 2010. 10(6): p. 405–16.PubMedCrossRefGoogle Scholar
  14. 14.
    Helmstädter, A., 100 Jahre Salvarsan: Chemisch auf Erreger zielen Pharmazeutische Zeitung, 2010. 52.Google Scholar
  15. 15.
    Domagk, G.J.P., Beitrag zur Chemotherapie der bakteriellen Infektionen. Deutsch. Med. Wochenschrift, 1935. 61: p. 250–253.CrossRefGoogle Scholar
  16. 16.
    Grundmann, E., Gerhard Domagk. Ein Pathologe besiegt die bakteriellen Infektionskrankheiten. Der Pathologe, 2001. 22.Google Scholar
  17. 17.
    Fischer, M., B. Thöny, and S. Leimkühler, The Biosynthesis of Folate and Pterins and Their Enzymology. Comprehensive Natural Products II: Chemistry and Biology ed. L.M.a.H.–W.B. Liu. Vol. 7. 2010, Oxford: Elsevier.Google Scholar
  18. 18.
    Reynolds, C.H., B.A. Tounge, and S.D. Bembenek, Ligand binding efficiency: trends, physical basis, and implications. J Med Chem, 2008. 51(8): p. 2432–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Fleischmann, R.D., et al., Whole–genome random sequencing and assembly of Haemophilus influenzae Rd. Science, 1995. 269(5223): p. 496–512.PubMedCrossRefGoogle Scholar
  20. 20.
    Blundell, T.L., H. Jhoti, and C. Abell, High–throughput crystallography for lead discovery in drug design. Nat Rev Drug Discov, 2002. 1(1): p. 45–54.PubMedCrossRefGoogle Scholar
  21. 21.
    Engelman, A. and P. Cherepanov, The structural biology of HIV–1: mechanistic and therapeutic insights. Nat Rev Microbiol, 2012. 10(4): p. 279–90.PubMedCrossRefGoogle Scholar
  22. 22.
    Jaskolski, M., et al., Structure at 2.5–A resolution of chemically synthesized human immunodeficiency virus type 1 protease complexed with a hydroxyethylene–based inhibitor. Biochemistry, 1991. 30(6): p. 1600–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Seelmeier, S., et al., Human immunodeficiency virus has an aspartic– type protease that can be inhibited by pepstatin A. Proc Natl Acad Sci U S A, 1988. 85(18): p. 6612–6.PubMedCrossRefGoogle Scholar
  24. 24.
    Kohl, N.E., et al., Active human immunodeficiency virus protease is required for viral infectivity. Proc Natl Acad Sci U S A, 1988. 85(13): p. 4686–90.PubMedCrossRefGoogle Scholar
  25. 25.
    Tie, Y., et al., Atomic resolution crystal structures of HIV–1 protease and mutants V82A and I84V with saquinavir. Proteins, 2007. 67(1): p. 232–42.PubMedCrossRefGoogle Scholar
  26. 26.
    Houston, J.G., The impact of automation on high–throughput screening. Methods Find Exp Clin Pharmacol, 1997. 19 Suppl A: p. 43–5.PubMedGoogle Scholar
  27. 27.
    Macarron, R., et al., Impact of high–throughput screening in biomedical research. Nat Rev Drug Discov, 2011. 10(3): p. 188–95.PubMedCrossRefGoogle Scholar
  28. 28.
    Snowden, M. and D.V. Green, The impact of diversity–based, highthroughput screening on drug discovery: "chance favours the prepared mind". Curr Opin Drug Discov Devel, 2008. 11(4): p. 553–8.PubMedGoogle Scholar
  29. 29.
    McInnes, C., Virtual screening strategies in drug discovery. Curr Opin Chem Biol, 2007. 11(5): p. 494–502.PubMedCrossRefGoogle Scholar
  30. 30.
    Rester, U., From virtuality to reality – Virtual screening in lead discovery and lead optimization: a medicinal chemistry perspective. Curr Opin Drug Discov Devel, 2008. 11(4): p. 559–68.PubMedGoogle Scholar
  31. 31.
    Rollinger, J.M., H. Stuppner, and T. Langer, Virtual screening for the discovery of bioactive natural products. Prog Drug Res, 2008. 65: p. 211, 213–49.Google Scholar
  32. 32.
    Metzker, M.L., Sequencing in real time. Nat Biotechnol, 2009. 27(2): p. 150–1.PubMedCrossRefGoogle Scholar
  33. 33.
    Metzker, M.L., Sequencing technologies – the next generation. Nat Rev Genet, 2010. 11(1): p. 31–46.PubMedCrossRefGoogle Scholar
  34. 34.
    Diacon, A.H., et al., The diarylquinoline TMC207 for multidrugresistant tuberculosis. N Engl J Med, 2009. 360(23): p. 2397–405.PubMedCrossRefGoogle Scholar
  35. 35.
    Haagsma, A.C., et al., Selectivity of TMC207 towards mycobacterial ATP synthase compared with that towards the eukaryotic homologue. Antimicrob Agents Chemother, 2009. 53(3): p. 1290–2.PubMedCrossRefGoogle Scholar
  36. 36.
    Matteelli, A., et al., TMC207: the first compound of a new class of potent anti-tuberculosis drugs. Future Microbiol, 2010. 5(6): p. 849–58.PubMedCrossRefGoogle Scholar
  37. 37.
    Shang, S., et al., Activities of TMC207, rifampin, and pyrazinamide against Mycobacterium tuberculosis infection in guinea pigs. Antimicrob Agents Chemother, 2011. 55(1): p. 124–31.PubMedCrossRefGoogle Scholar
  38. 38.
    Baker, M., Fragment-based lead discovery grows up. Nat Rev Drug Discov, 2013. 12(1): p. 5–7.PubMedCrossRefGoogle Scholar
  39. 39.
    Erlanson, D.A., Introduction to fragment-based drug discovery. Top Curr Chem, 2012. 317: p. 1–32.PubMedGoogle Scholar
  40. 40.
    Rees, D.C., et al., Fragment-based lead discovery. Nat Rev Drug Discov, 2004. 3(8): p. 660–72.PubMedCrossRefGoogle Scholar
  41. 41.
    Clarke, T., Drug companies snub antibiotics as pipeline threatens to run dry. Nature, 2003. 425(6955): p. 225.Google Scholar
  42. 42.
    Madigan, M.T., J.M. Matinko, and J. Parker, Brock Miikrobiologie. Vol. 1. Auflage. 2001, Heidelberg, Berlin: Spektrum Akademischer Verlag.Google Scholar

Copyright information

© Springer Fachmedien Wiesbaden 2014

Authors and Affiliations

  1. 1.HAMBURG SCHOOL OF FOOD SCIENCE, Institut für LebensmittelchemieUniversität HamburgHamburgDeutschland

Personalised recommendations