The
View from Here
Geoffrey Pasvol
This editor's choice expands on the multiplicity of approaches, new and old, in the pharmacological assault on malaria. These approaches are outlined here...
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more...
Upcoming Issues
Issue 12/December '06
A review of 2006
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Top
Reviews
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Targeting DHFR in parasitic protozoa
Amy C. Anderson
Drug Discovery Today
Parasitic apicomplexans are responsible for some of the most severe worldwide
health problems, including malaria, toxoplasmosis and cryptosporidiosis. These
parasites are characterized by a bifunctional enzyme, dihydrofolate reductasethymidylate
synthase (DHFR-TS), which has a crucial role in pyrimidine biosynthesis.
Inhibitors of DHFR have been successful in the treatment of toxoplasmosis and
malaria. However, there is currently no effective therapy for cryptosporidiosis, and
despite early successes against malaria, resistance to DHFR inhibitors in malaria
parasites has now become a global problem. Novel DHFR inhibitors, designed using
the recently revealed crystal structures of the enzymes from two parasitic protozoa, are in development...
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Heme detoxification and antimalarial drugs - Known mechanisms and future prospects
Dharmendar Rathore, Dewal Jani, Rana Nagarkatti and Sanjai Kumar
Drug Discovery Today
Malaria parasite degrades hemoglobin and releases toxic heme, which is quickly detoxified by the parasite.
Whereas several important antimalarials like artemisinin and chloroquine disrupt this process, the mechanism
of heme detoxification is not fully understood and is a subject of intense debate. This review summarizes
the current state of research in heme detoxification, its future directions and reasons why this process has been and will remain one of the most attractive targets for developing antimalarials...
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Inhibitors of de novo folate enzymes in Plasmodium falciparum
Alexis Nzila
Drug Discovery Today
Antifolates, inhibitors of folate synthesis or folate conversion, are used for malaria treatment. They are
developed as synergistic combinations of inhibitors of dihydrofolate reductase (DHFR) and of
dihydropteroate synthase (DHPS). DHPS inhibitors are sulfur-based drugs, analogs of sulfanilamide.
These compounds compete with para-aminobenzoic acid in the active site of DHPS. The discovery of new
antifolates is based on the identification of DHFR inhibitors; little work has been done on sulfur-based
drugs because of their toxicity. As a result, only a few sulfur-based drugs are available. In this review, the
hypothesis that compounds that compete with pteridine derivatives in active sites of de novo folate
enzymes can be used as synergizers of DHFR inhibitors is discussed. If correct, this could lead to the
identification of a new family of synergizers of DHFR inhibitors...
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Abstracts of Key Research Articles
Engineering a mevalonate pathway in Escherichia coli for production of terpenoids
Martin V.J. et al.
Nat Biotechnol (2003) 21(7):796-802
A randomized trial of artemether-lumefantrine versus mefloquine-artesunate for the treatment of uncomplicated multi-drug resistant Plasmodium falciparum on the western border of Thailand
Hutagalung R. et al.
Malar J 4:46
Effect of artemether-lumefantrine policy and improved vector control on malaria burden in KwaZulu-Natal, South Africa
Barnes K.I. et al.
PLoS Med (2005) 49(2):534-53
Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial
Dondorp A. et
al.
Lancet (2005) 366(9487):717-25
Comparative pharmacokinetics of intramuscular artesunate and artemether in patients with severe falciparum malaria
Hien T.T. et
al.
Antimicrob Agents Chemother (2004) 48(11):4234-9
Efficacy of rectal artesunate compared with parenteral quinine in initial treatment of moderately severe malaria in African children and adults: a randomised study
Barnes K.I. et al.
Lancet (2004) 363(9421):1598-605
Azithromycin combination therapy with artesunate or quinine for the treatment of uncomplicated Plasmodium falciparum malaria in adults: a randomized, phase 2 clinical trial in Thailand
Noedl H. et al.
Clin Infect Dis (2006) 43(10):1264-71
Return of chloroquine antimalarial efficacy in Malawi
Laufer M.K. et al.
The New England journal of medicine (2006) 355(19):1959-66
Malaria vaccines: New hope in old ideas
Pinzon-Charry et al.
Drug Discovery Today: Therapeutic strategies (2006) 3(2): 167-172 |
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Biomarker Workshop III
World Drug Discovery & Development Summit
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