17/08/06

Hybrid molecule could treat drug resistant malaria

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A drug that was one of the main tools for treating malaria until the parasite grew resistant to it could still have a major role in fighting the disease.

Researchers have made the drug — chloroquine — effective against even chloroquine-resistant malaria by binding it with another chemical. The research, led by David Peyton of Portland State University, United States, was published on 12 August in the Journal of Medical Chemistry.

Since the 1990s, researchers have been experimenting with chemicals that seem to block the malarial proteins that confer drug resistance.

Peyton’s team attached one of these ‘reversal agents’ to chloroquine to produce a single hybrid molecule. They then tested its effectiveness against the malaria parasite Plasmodium falciparum in the laboratory.

The ‘reversed chloroquine’ was at least as effective against chloroquine-resistant parasites as chloroquine is against non-resistant malaria.

The drug was also effective in mice infected with Plasmodium chabaudi, which causes malaria in rodents. There were no obvious side effects.

Peyton said that, although several chemicals act as reversal agents, the doses needed are generally higher than with reversed chloroquine. His team is currently developing related molecules with improved qualities.

Sanjeev Krishna, a professor of parasitology at St. George’s Hospital Medical School in London, United Kingdom, says that different approaches to the problem of drug-resistant malaria are always welcome.

But he points out that whether a promising compound enters drug development would depend on factors such as the cost and ease of producing it, and how the chemical acts when taken.

Link to abstract of paper in the Journal of Medical Chemistry

Reference: Journal of Medical Chemistry doi 10.1021/jm060399n S0022-2623(06)00399-2

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