A group of researchers from 16 institutions around the world has identified a new class of anti-malarial compounds that target multiple stages of the malaria parasite's life cycle (http://www.niaid.nih.gov/topics/malaria/pages/lifecycle.aspx). These compounds could potentially be developed into drugs that treat and prevent malaria infection. Known as 4-(1H)-quinolone-3-diarylethers, the candidate anti-malarials are derived from a compound called endochin that effectively treats malaria in birds. When tested in the laboratory and in mice, the compounds demonstrated strong activity against Plasmodium falciparum and Plasmodium vivax, the two parasites that cause most human cases of malaria. Transmitted via a mosquito bite, malaria causes cycles of chills, fever and fatigue, and is responsible for roughly 660,000 deaths per year, according to the World Health Organization. New drugs are needed because of the emergence of malaria-inducing parasites that are resistant to existing medications.
Of the 4-(1H)-quinolones, the researchers focused their efforts on the compound ELQ-300, which inhibited malaria parasites during the erythrocytic stage, when they cause symptoms in humans; as well as during the gametocyte and developmental stages in the mosquito, when the parasites are transmitted. In addition, when ELQ-300 was administered to mice infected with the Plasmodium species that cause malaria in mice, the infection was cured. The study results also suggested that the compound could be adapted into a once-daily dose in humans and would be slow to engender resistance. The researchers are currently proceeding with preclinical development of ELQ-300.
The study, which will be published March 20, was supported by the National Institute of Allergy and Infectious Diseases and the National Institute of General Medical Sciences, both part of the National Institutes of Health; the Wellcome Trust; and Medicines for Malaria Venture.
ARTICLE: Nilsen A et al. Quinolone-3-diarylethers: A new class of drugs for a new era of malaria eradication. Science Translational Medicine DOI: 10.1126/scitranslmed.3005029 (2013).
M. John Rogers, Ph.D., a biologist in NIAID's Parasitology and International Programs Branch, is available to discuss the findings.
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