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Discovering New Medicines to Control and Eradicate Malaria

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Third World Diseases

Part of the book series: Topics in Medicinal Chemistry ((TMC,volume 7))

Abstract

Malaria is one of the most devastating diseases the world has ever known affecting almost 250 million people a year and resulting in over 860,000 deaths, mostly of children under the age of 5 years. With increased funding and the advent of public–private partnerships such as Medicines for Malaria Venture, the search for new medicines to combat malaria has, over the last decade, undergone a renaissance. This is both as a result of increased funding and the recent development of new tools, such as high-throughput screening technology. In addition, public and political attention has been caught by calls from the Gates Foundation and World Health Organization for a strategy to eradicate malaria once and for all. This will mean having therapeutics to combat not only Plasmodium falciparum malaria – predominantly found in Africa – but also Plasmodium vivax malaria, which is endemic in many parts of Asia and South America. However, as with all infectious disease, there is a constant threat of drug resistance, and therefore the continual need for new medicines. In this review, we summarise the challenges posed by malaria drug discovery and development. We present the pipeline of existing treatments and those in clinical development. New modes of action are under investigation in preclinical discovery, and we review the opportunities as well as the risks to these early stage projects.

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Notes

  1. 1.

    All structures are referenced within other cited articles except the following: CDRI 97/98 is exemplifed in: Singh C, Puri SK (2001) US 6316493.

  2. 2.

    CEM-101 is exemplified in: Liang C-H, Duffield J, Romero A, Chiu Y-H, Rabuka D, Yao S, Sucheck S, Marby K, Shue Y-K, Ichikawa Y, Hwang C-K (2004) WO 2004080391.

  3. 3.

    P218 is exemplified in: Tarnchompoo B, Yuthavong Y, Vilaivan T, Chitnumsub P, Thongpanchang C, Kamchonwongpaisan S, Matthews D, Vivas L, Yuvaniyama J, Charman S, Charman W, Katiyar SB (2009) WO 2009048957.

  4. 4.

    OZ439 is exemplified in: Vennerstrom JL, Dong Y, Charman SA, Wittlin S, Chollet J, Creek DJ, Wang X, Sriraghavan K, Zhou L, Matile H, Charman WN (2009) WO 2009058859.

  5. 5.

    NITD609 is exemplified in: Ang SH, Krastel P, Leong, SY, Tan LJ, Wong WLJ, Yeung BK, Zou B (2009) WO 2009132921.

  6. 6.

    BCX4208 is exemplified in: Evans GB, Furneaux RH, Lenz DH, Schramm, VL, Tyler PC, Zubkova OV (2004) WO 2004018496.

  7. 7.

    http://www.dpd.cdc.gov/dpdx/html/PDF_Files/Pfalciparum_benchaidV2.pdf

  8. 8.

    http://www.ebi.ac.uk/chemblntd; http://www.collaborativedrug.com/; http://pubchem.ncbi.nlm.nih.gov/

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Acknowledgements

The authors would like to thank the Central Drug Research Institute, India (CDRI), for allowing the disclosure of the structure of CDRI 97/98. Also special thanks to MMV staff, in particular Dr. T. Wells, Dr. D. Leroy and E. Poll for helpful discussions, suggestions and proof-reading.

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    Jeremy N. Burrows & David Waterson

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Burrows, J.N., Waterson, D. (2011). Discovering New Medicines to Control and Eradicate Malaria. In: Elliott, R. (eds) Third World Diseases. Topics in Medicinal Chemistry, vol 7. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7355_2011_14

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