MD-Stipendium Sommer

Characterisation of the anti-malarial properties of Dehalogenil

01/04/2025 to 30/09/2026

Even in the 21st century Malaria still poses a challenge for many communities worldwide. Alone in 2023 the disease was linked to 597 000 cases of death. The plasmodium parasite is transmitted by the bite of a female Anopheles mosquito. Inside the host’s body it undergoes asexual hepatic and erythrocytic life stages. During the latter one some of the parasites switch their path of development and form into so called Gametocytes. These Gametocytes are able to be taken up by mosquitos, in which they sexually reproduce forming a new generation of Plasmodia. Therefore, Gametocytes constitute the key stage in the parasite’s transmission.
Nonetheless, among the widely used therapy regimens (Artemisinin-based combination therapies or “ACTs”) only few are able to effectively target Gametocytes. Furthermore, the therapy’s backbone Artemisinin has become the target of drug resistances. These first appeared in the Mekong-region but were independently detected on the African continent as well. That is why concern regarding a loss of effectiveness of seasoned therapy regimens is growing.
To counteract these developments research into new antimalarials has already picked up pace. One promising candidate for a new antimalarial is the Macrolide Chlorotonil. Its precise mode of action still awaits comprehensive characterisation, but it seems to be diverging from established antimalarials such as Artemisinin and Chloroquin. In-vitro assays on the compound indicated towards some desirable traits. It displayed high biological activity against laboratory strains as well as clinical isolates from Gabon, its onset of action is fast and it even showed effective against Gametocytes. Further in-vivo experiments on mice infected with Plasmodium berghei underscored the positive outlook on the substance’s effects.
The focus now lies on the properties of its derivate Dehalogenil. Through its increased water-solubility, higher in-vivo stability and reduced toxicity in animal experiments this substance might combine easier application with the favourable aspects of Chlorotonil. Our project is focussing on the repetition of assays established for the evaluation of Chlorotonil on the new agent of Dehalogenil. In this way we are reviewing if the compound stands up to the benchmarks of its predecessor e.g. its fast effect against mature Gametocytes. Therefore, our study might yield valuable information if this promising compound could constitute a worthwhile subject of further steps of research as an alternative for Chlorotonil.