Potential new antimalarial could both kill the parasite and overcome its resistance to other drugs

from Paul Chinook, TropIKA.net

Researchers in the USA have reported encouraging results with the use of an acridone derivative against malarial parasites in vitro and in mice. In their study, published in Nature, they describe also their finding that the drug reverses the resistance the parasite has developed to other drugs, including chloroquine.

The acridone derivative - T3.5 (3-chloro-6-(2-diethylamino-ethoxy)-10-(2-diethylamino-ethyl)-acridone) - targets the ability of the parasite to convert haem, present in human blood and toxic to the parasite, into haemozoin. If this conversion is prevented then the parasite will die. Existing antimalarials, including quinine and chloroquine, also have this mode of action. However, the parasite has developed the ability to prevent the absorption of such older drugs. T3.5 seems to be able to disable that defence mechanism, thus restoring the effectiveness of these drugs.

Speaking to the BBC, Dr Mike Riscoe from Portland State University who worked on the study, said: "What we wanted was to design a molecule that would be of itself an antimalarial drug, but that would have the power to work together with drugs like chloroquine and quinine, even against parasites that were resistant to those drugs. We would hope to make existing drugs like chloroquine and quinine useful again, so combining those with this new one could help to combat the rising tide of drug resistance".

However, Dr Jane Kelly, who led the research, warned: "In the pharmaceutical industry, it can take 10 years and $1bn for a drug to be usable in humans, so we are still a long way away from that." Further animal research and safety studies will be required before human trials can be considered.

Reference:
1. Kelly JX, Smilkstein MJ, Brun R, Wittlin S, Cooper RA, Lane KD, Janowsky A, Johnson RA, Dodean RA, Winter R, Hinrichs DJ, Riscoe MK (2009). Discovery of dual function acridones as a new antimalarial chemotype. Nature. 8 Apr. [Epub ahead of print].

Available from: https://www.ncbi.nlm.nih.gov/pubmed/19357645