Challenges in antimalarial drug discovery

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

Bibliography

• 1  Wells TNC, Alonso PL, Gutteridge WE. New medicines to improve control and contribute to the eradication of malaria. Nat. Rev. Drug Disc.8,879–891 (2009).▪ Summarizes the disease, life cycle and current treatments, providing a good overall foundation.
  Medline CASGoogle Scholar
• 2  Olliaro P, Wells TNC. The global portfolio of new antimalarial medicines under development. Clin. Pharm. Ther.85(6),584–595 (2009).
  Medline CASGoogle Scholar
• 3  Bathurst I, Hentschel C. Medicines for Malaria Venture: sustaining antimalarial drug development. Trends Parasit.22(7),301–307 (2009).
  Google Scholar
• 4  Alonso PL, Brown G, Arevalo-Herrera M et al. A research agenda for malaria eradication: drugs. PLoS medicine.8(1),e1000406 (2011).
  MedlineGoogle Scholar
• 5  Fidock DA, Rosenthal PJ, Croft SA, Brun R, Nwaka S. Antimalarial drug discovery: efficacy models for compound screening. Nat. Rev. Drug Discov.3,509–520 (2004).▪▪ Key article outlining antimalarial drug discovery, including pathways, assays and assay protocols.
  Medline CASGoogle Scholar
• 6  Burrows JN, Waterson D. Discovering new medicines to control and eradicate malaria. In: Diseases of the Developing World. Elliot R (Ed.). Springer, Washington, DC, USA (2011).
  Google Scholar
• 7  Gamo FJ, Sanz LM, Vidal J et al. Thousands of chemical starting points for antimalarial lead identification. Nature465,305–310 (2010).
  Medline CASGoogle Scholar
• 8  Plouffe D, Brinker A, McNamara C et al.In silico activity profiling reveals the mechanism of action of antimalarials discovered in a high-throughput screen. PNAS105(26),9059–9064 (2008).
  Medline CASGoogle Scholar
• 9  Guiguemde WA, Shelat AA, Bouck D et al. Chemical genetics of Plasmodium falciparum. Nature465,311–315 (2010).
  Medline CASGoogle Scholar
• 10  Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev.23,3–25 (1997).
  CASGoogle Scholar
• 11  Ridgway D, Tuszynski JA, Tam YK. reassessing models of hepatic extraction. J. Biol. Phys.29(1),1–21 (2003).
  Medline CASGoogle Scholar
• 12  Fry JR. The metabolism of drugs by isolated hepatocytes. Q. Rev. Drug Metab. Drug Interact.4,99–122 (1982).
  Medline CASGoogle Scholar
• 13  Peters W, Robinson BL. Malaria In: Handbook of Animal Models of Infection. Zak O, Sande M (Eds). Academic Press, London, UK 757–773 (1999).
  Google Scholar
• 14  Angulo-Barturen I, Jimenez-Diaz MB, Mulet T et al. A murine model of falciparum-malaria by in vivo selection of competent strains in non-myelodepleted mice engrafted with human erythrocytes. PloS one.3(5),e2252 (2008).
  MedlineGoogle Scholar
• 15  Lagrutta AA, Trepakova ES, Salata JJ. The hERG channel and risk of drug-acquired cardiac arrhythmia: an overview. Curr. Topics Med. Chem.8(13),1102–1112 (2008).
  Medline CASGoogle Scholar
• 16  Kirkland D, Reeve L, Gatehouse D, Vanparys P. A core in vitro genotoxicity battery comprising the Ames test plus the in vitro micronucleus test is sufficient to detect rodent carcinogens and in vivo genotoxins. Mutat. Res.721(1),27–73 (2011).
  Medline CASGoogle Scholar
• 17  Hamon J, Whitebread S, Techer-Etienne V, Le Coq H, Azzaoui K, Urban L. In vitro safety pharmacology profiling: what else beyond hERG? Future Med. Chem.1(4),645–665 (2009).
  CASGoogle Scholar
• 18  Sinden RE. Malaria, sexual development and transmission: retrospect and prospect. Parasitology136(12),1427–1434 (2009).
  Medline CASGoogle Scholar
• 19  Bousema T, Okell L, Shekalaghe S et al. Revisiting the circulation time of Plasmodium falciparum gametocytes: molecular detection methods to estimate the duration of gametocyte carriage and the effect of gametocytocidal drugs. Malar. J.9,136 (2010).
  MedlineGoogle Scholar
• 20  Delves M, Sinden RE. A semi-automated method for counting fluorescent malaria oocysts increases the throughput of transmission blocking studies. Malar. J.9,35 (2010).
  MedlineGoogle Scholar
• 21  Buchholz K, Burke TA, Williamson KC, Wiegand RC, Wirth DF, Marti M. A high-throughput screen targeting malaria transmission stages opens new avenues for drug development. J. Infect. Dis.203(10),1445–1453 (2011).
  MedlineGoogle Scholar
• 22  Tanaka TQ, Williamson KC. A malaria gametocytocidal assay using oxidoreduction indicator, alamarBlue. Mol. Biochem. Parasitol.177(2),160–163 (2011).
  Medline CASGoogle Scholar
• 23  Rodríguez MC, Margos G, Compton H et al.Plasmodium berghei: routine production of pure gametocytes, extracellular gametes, zygotes, and ookinetes. Exp. Parasitol.101,73–76 (2002).
  Medline CASGoogle Scholar
• 24  Peatey CL, Skinner-Adams TS, Dixon MWA, McCarthy JS, Gardiner DL, Trenholme KR. Effect of antimalarial drugs on Plasmodium falciparum gametocytes. J. Infect. Dis.200(10),1518–1521 (2009).▪ The authors describe effects of drugs on gametocyte number and viability of late-stage parasites.
  MedlineGoogle Scholar
• 25  Mazier D, Beaudoin RL, Mellouk S et al. Complete development of hepatic stages of Plasmodium falciparumin vitro. Science227(4685),440–442 (1985).
  Medline CASGoogle Scholar
• 26  Ploemen IHJ, Prudencio M, Douradinha BG et al. Visualisation and quantitative analysis of the rodent malaria liver stage by real time imaging. PloS one.4(11),e7881 (2009).
  MedlineGoogle Scholar
• 27  Price RN, Tjiltra E, Guerra CA, Yeung S, White NJ, Anstey NM. Vivax malaria: neglected and not benign. Am. J. Trop. Med. Hyg.77(Suppl. 6),79–87 (2007).
  MedlineGoogle Scholar
• 28  Wells TNC, Burrows JN, Baird JK. Targeting the hypnozoite reservoir of Plasmodium vivax: the hidden obstacle to malaria elimination. Trends Parasit.26(3),145–151 (2010).▪ Takes a fresh look at the challenges presented by hypnozoites, summarizing the state of the art.
  MedlineGoogle Scholar
• 29  Mazier D, Landau I, Druilhe P et al. Cultivation of the liver forms of Plasmodium vivax in human hepatocytes. Nature307(5949),367–369 (1984).
  Medline CASGoogle Scholar
• 30  Chattopadhyay R, Velmurugan S, Chakiath C et al. Establishment of an in vitro assay for assessing the effects of drugs on the liver stages of Plasmodium vivax malaria. PLoS One5(12),e14275 (2010).▪ The authors discuss a Plasmodium vivax liver-stage assay.
  MedlineGoogle Scholar
• 31  Carraz M, Jossang A, Rasoanaivo P, Mazier D, Frappier F. Isolation and antimalarial activity of new morphinan alkaloids on Plasmodium yoelii liver stage. Bioorg. Med. Chem.16(11),6186–6192 (2008).
  Medline CASGoogle Scholar
• 32  Mwakingwe A, Ting LM, Hochman S, Chen J, Sinnis P, Kim K. Noninvasive real-time monitoring of liver-stage development of bioluminescent Plasmodium parasites. J. Inf. Dis.200(9),1470–1478 (2009).
  Medline CASGoogle Scholar
• 33  Gego A, Silvie O, Franetich JF et al. New approach for high-throughput screening of drug activity on Plasmodium liver stages. Antimicrob. Agents Ch.50(4),1586–1589 (2006).
  Medline CASGoogle Scholar
• 34  Westenberger SJ, McClean CM, Chattopadhyay R et al. A systems-based analysis of Plasmodium vivax lifecycle transcription from human to mosquito. PLoS Negl. Trop. Dis.4(4),e653 (2010).
  MedlineGoogle Scholar
• 35  Dembele L, Gego A, Zeeman AM. Towards an in vitro model of Plasmodium hypnozoites suitable for drug discovery. PLoSOne6(3),e18162 (2011).▪ With Plasmodium cynomolgi as a surrogate for Plasmodium vivax malaria, the authors discuss the chemical validation of a liver-stage assay, through the selective killing of small parasite forms.
  Medline CASGoogle Scholar
• 36  Schmidt LH. Relationships between chemical structures of 8-aminoquinolines and their capacities for radical cure of infections with Plasmodium cynomolgi in rhesus monkeys. Antimicrob. Agents Ch.615–652 (1983).▪ Although an old article, Schmidt gives an outstanding account of liver-stage Plasmodium vivax drug discovery.
  MedlineGoogle Scholar
• 37  Bass A, Kinter L, Williams P. Origins, practices and future of safety pharmacology. J. Pharmacol. Toxicol. Methods49(3),145–151 (2004).
  Medline CASGoogle Scholar
• 38  Young RD, Rathod PK. Clonal viability measurements on Plasmodium falciparum to assess in vitro schizonticidal activity of leupeptin, chloroquine, and 5-fluoroorotate. Antimicrob. Agents Ch.37(5),1102–1107 (1993).
  Medline CASGoogle Scholar
• 39  Painter HJ, Morrisey JM, Vaidya AB. Mitochondrial electron transport inhibition and viability of intraerythrocytic Plasmodium falciparum. Antimicrob. Agents Chemother.54(12),5281–5287 (2010).
  Medline CASGoogle Scholar
• 40  Barnes KI, Watkins WM, White NJ. Antimalarial dosing regimens and drug resistance. Trends Parasit.24(3),127–134 (2008).
  Medline CASGoogle Scholar
• 41  Ambrose PG, Bhavnani SM, Rubino CM et al. Pharmacokinetics-pharmacodynamics of antimicrobial therapy: it’s not just for mice anymore. Clin. Infect. Dis.44(1),79–86 (2007).
  Medline CASGoogle Scholar
• 42  Rathod PK, Mcerlean T, Lee PC. Variations in frequencies of drug resistance in Plasmodium falciparum. PNAS94(17),9389–9393 (1997).
  Medline CASGoogle Scholar
• 43  Simpson JA, Watkins ER, Price RN, Aarons L, Kyle DE, White NJ. Mefloquine pharmacokinetic-pharmacodynamic models: implications for dosing and resistance. Antimicrob. Agents Chemother.44,3414–3424 (2000).▪ The modeling performed on mefloquineserves as a foundation for studies with future clinical compounds and combinations.
  Medline CASGoogle Scholar
• 101  World Health Organization. World Malaria Report 2010. www.who.int/malaria/world_malaria_report_2010/en/index.html
  Google Scholar
• 102  Medicines for Malaria Venture. Malaria lifecycle. http://www.mmv.org/about-us/malaria-and-medicines/parasite-lifecycle
  Google Scholar
• 103  World Health Organization. Malaria treatment guidelines 2010. www.who.int/malaria/publications/atoz/9789241547925/en/index.html
  Google Scholar
• 104  Medicines for Malaria Venture. Target product profiles. www.mmv.org/research-development/essential-information-scientists/target-product-profiles
  Google Scholar
• 105  Medicines for Malaria Venture. Compound Progression criteria. www.mmv.org/research-development/essential-information-scientists
  Google Scholar