Encyclopedia of Malaria

Living Edition
| Editors: Peter G. Kremsner, Sanjeev Krishna

Druggable Biochemical Targets: Facts and Fancies

  • Eric Maréchal
Living reference work entry
DOI: https://doi.org/10.1007/978-1-4614-8757-9_56-1

Synonyms

Definition

Biochemical target: macromolecule (protein or non-protein) that is (i) vital for the malaria parasite, or critical for its interaction and propagation within the human host, and (ii) functionally blocked by a drug.

What Is a Biochemical Target?

In medical sciences, the notion of target is versatile enough to be used in various, sometimes overlapping, meanings, qualifying any biological object and/or phenomenon, one aims to act on as part of a therapy. It follows that a targetcan be defined at different scales, as a phenotype expressed by the patient (e.g., symptoms including fever, weakness, and pain), a biological process causing the disease (e.g., a vital metabolic pathway in the pathogen or a molecular mechanism involved in the infection), a subcellular structure (e.g., a vital organelle of the pathogen), a protein (e.g., a vital enzyme of a pathogen), a protein domain (e.g., a “pocket” at the surface of a protein, where a drug can dock;...

Keywords

Antimalarial Drug Dihydrofolate Reductase Sesquiterpene Lactone Cinchona Alkaloid Drug Development Program 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

References

  1. Aurrecoechea C, Brestelli J, Brunk BP, Dommer J, Fischer S, Gajria B, et al. PlasmoDB: a functional genomic database for malaria parasites. Nucleic Acids Res. 2009;37(Database issue):D539–43.PubMedCentralPubMedCrossRefGoogle Scholar
  2. Baird JK. Effectiveness of antimalarial drugs. N Engl J Med. 2005;352(15):1565–77.PubMedCrossRefGoogle Scholar
  3. Botté CY, Dubar F, McFadden GI, Maréchal E, Biot C. Plasmodium falciparum apicoplast drugs: targets or off-targets? Chem Rev. 2012;25(112):1269–83.CrossRefGoogle Scholar
  4. Bray PG, Ward SA, O’Neill PM. Quinolines and artemisinin: chemistry, biology and history. Curr Top Microbiol Immunol. 2005;295:3–38.PubMedGoogle Scholar
  5. Camara D, Bisanz C, Barette C, Van Daele J, Human E, Barnard B, et al. Inhibition of p-aminobenzoate and folate syntheses in plants and apicomplexan parasites by natural product rubreserine. J Biol Chem. 2012;287(26):22367–76.PubMedCentralPubMedCrossRefGoogle Scholar
  6. Cohen SN, Phifer KO, Yielding KL. Complex formation between chloroquine and ferrihaemic acid in vitro, and its effect on the antimalarial action of chloroquine. Nature. 1964;202:805–6.PubMedCrossRefGoogle Scholar
  7. Ecker A, Lehane AM, Clain J, Fidock DA. PfCRT and its role in antimalarial drug resistance. Trends Parasitol. 2012;28(11):504–14.PubMedCentralPubMedCrossRefGoogle Scholar
  8. Farooq U, Mahajan RC. Drug resistance in malaria. J Vector Borne Dis. 2004;41(3-4):45–53.PubMedGoogle Scholar
  9. Flückiger FA, Hanbury D. Pharmacographia: a history of the principal drugs of vegetable origin, met with in Great Britain and British India. London: Macmillan; 1874.Google Scholar
  10. Foley M, Tilley L. Quinoline antimalarials: mechanisms of action and resistance and prospects for new agents. Pharmacol Ther. 1998;79(1):55–87.PubMedCrossRefGoogle Scholar
  11. Gardner MJ, Hall N, Fung E, White O, Berriman M, Hyman RW, et al. Genome sequence of the human malaria parasite Plasmodium falciparum. Nature. 2002;419(6906):498–511.PubMedCrossRefGoogle Scholar
  12. Ginsburg H. Progress in in silico functional genomics: the malaria metabolic pathways database. Trends Parasitol. 2006;22(6):238–40.PubMedCrossRefGoogle Scholar
  13. Gorka AP, de Dios A, Roepe PD. Quinoline drug-heme interactions and implications for antimalarial cytostatic versus cytocidal activities. J Med Chem. 2013;56:5231–46.PubMedCrossRefGoogle Scholar
  14. Holt RA, Subramanian GM, Halpern A, Sutton GG, Charlab R, Nusskern DR, et al. The genome sequence of the malaria mosquito Anopheles gambiae. Science. 2002;298(5591):129–49.PubMedCrossRefGoogle Scholar
  15. Kappe SH, Vaughan AM, Boddey JA, Cowman AF. That was then but this is now: malaria research in the time of an eradication agenda. Science. 2010;328(5980):862–6.PubMedCrossRefGoogle Scholar
  16. Kaur K, Jain M, Reddy RP, Jain R. Quinolines and structurally related heterocycles as antimalarials. Eur J Med Chem. 2010;45(8):3245–64.PubMedCrossRefGoogle Scholar
  17. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, et al. Initial sequencing and analysis of the human genome. Nature. 2001;409(6822):860–921.PubMedCrossRefGoogle Scholar
  18. Laveran A. Nature parasitaire des accidents de l’impaludisme. Description d’un nouveau parasite trouvé dans le sang des malades atteints de fièvre palustre. Paris: J-B Baillière et fils; 1881.Google Scholar
  19. Maréchal E. Chemogenomics: a discipline at the crossroad of high throughput technologies, biomarker research, combinatorial chemistry, genomics, cheminformatics, bioinformatics and artificial intelligence. Comb Chem High Throughput Screen. 2008;11(8):582.PubMedCrossRefGoogle Scholar
  20. Nerlich AG, Schraut B, Dittrich S, Jelinek T, Zink AR. Plasmodium falciparum in ancient Egypt. Emerg Infect Dis. 2008;14(8):1317–9.PubMedCentralPubMedCrossRefGoogle Scholar
  21. Nzila A. The past, present and future of antifolates in the treatment of Plasmodium falciparum infection. J Antimicrob Chemother. 2006;57(6):1043–54.PubMedCrossRefGoogle Scholar
  22. O’Neill PM, Barton VE, Ward SA. The molecular mechanism of action of artemisinin–the debate continues. Molecules. 2010;15(3):1705–21.PubMedCrossRefGoogle Scholar
  23. Olliaro P. Mode of action and mechanisms of resistance for antimalarial drugs. Pharmacol Therapeut. 2001;89(2):207–19.CrossRefGoogle Scholar
  24. Saidani N, Grando D, Valadie H, Bastien O, Maréchal E. Potential and limits of in silico target discovery – case study of the search for new antimalarial chemotherapeutic targets. Infect Genet Evol. 2009;9(3):359–67.PubMedCrossRefGoogle Scholar
  25. Sakata T, Winzeler EA. Genomics, systems biology and drug development for infectious diseases. Mol Biosyst. 2007;3(12):841–8.PubMedCrossRefGoogle Scholar
  26. Woodrow CJ, Haynes RK, Krishna S. Artemisinins. Postgrad Med J. 2005;81(952):71–8.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Laboratoire de Physiologie Cellulaire VégétaleUnité mixte de recherche 5168 CNRS – CEA – UnivGrenobleFrance