Medical Research

New Agent Against Tropical Parasite

1. 8. 2012 | There is an urgent demand for better drugs to treat the African sleeping sickness. Scientists of Würzburg University, among them the research group of professor Ulrike Holzgrabe, have now developed a very promising new agent. Next, this agent needs to be further improved and tested extensively.
African sleeping sickness is caused by the tropical parasite Trypanosoma brucei. This unicellular, worm-shaped organism is endemic in Sub-Saharan Africa. It is transmitted to humans through the bite of the tsetse fly. Infected people first suffer from headaches and aching limbs. Later on, confusion, spasms and other symptoms set in. Finally, the patients enter a kind of vegetative state and die. About 30,000 new infections occur each year. There are still no vaccines available against the pathogen, and the drugs on offer sometimes have extreme side effects. Therefore, better drugs are urgently needed for the treatment of this disease. Pharmacologists, medical researchers and biologists of the University of Würzburg have found a new potent agent against trypanosoma, and presented their findings in the "Journal of Medicinal Chemistry".
African sleeping sickness
Bild vergrößern
(© Georg Hiltensperger / Nicola Jones)

African sleeping sickness | The parsite before (left) and after the treatment with the active agent: the cell contents are jumbled (green: mitochondrion, dark blue: nucleus, light blue: kinetoplast)

The new agent is a molecule classified into the group of "quinolone amides". It has been developed by Würzburg pharmacologists. In cell cultures, the agent reliably kills off the pathogens responsible for the sleeping sickness – even when administered in small doses. How does the quinolone amide attack the parasites? Analyses at the Biocenter have shown that the agent interacts with the so-called kinetoplasts. These structures are only found in trypanosomes. "Without the kinetoplasts, the cell division and consequently the reproduction of the pathogens halts", says Nicola Jones of the Biocenter Würzburg.

Next, it must be clarified in an animal model whether the new agent works effectively in an infected organism as well. However, there is still a hurdle to be cleared before doing this. Quinolone amide is poorly soluble in water. "Therefore, processing it into a drug is very difficult. Furthermore, the agent is not absorbed into the blood effectively enough", explains Georg Hiltensperger at the Department of Pharmaceutical Chemistry.
So the bioavailability of the agent still needs to be improved. To achieve this, the researchers pursue two strategies. Firstly, they are testing whether the quinolone amide can be made more water soluble without loss of effectiveness, by means of chemical modifications. Secondly, they are trying to encapsulate the agent with pharmaceutical technologies so effectively that it may be delivered to the blood in sufficient quantities after oral administration.

The scientists at the University of Würzburg involved in this research include the study groups of professors Ulrike Holzgrabe and Lorenz Meinel (Pharmacy), Markus Engstler (Biology) and Holger Braunschweig (Chemistry). The tropical medicine expert August Stich of the Medical Mission Institute Würzburg and the Basel researcher Marcel Kaiser are also contributing to this research. The results were achieved at the Collaborative Research Center (SFB) 630 "Recognition, Preparation and Functional Analysis of Agents against Infectious Diseases" of the University of Würzburg. The SFB is funded by the German Research Foundation.   (© Julius-Maximilians-Universität Würzburg)
Robert Emmerich

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