Recently, national and international health authorities have declare war on multiresistant bacteria. Beside the growing problem of resistances, a lot of bacterial infections cannot be sufficiently treated because no appropriate anti-infectives are available. Among them are protozoal diseases such as sleeping sickness and leishmaniosis, as well as infections by gram-negative bacteria like Legionella and Burkholderia.
Within the frame of the DFG-funded collaborative research center 630, dealing mainly with tropical infectious diseases, we have developed new quinolone amides which are able to cure Trypanosoma brucei infected mice.[[i]]
Extracts from Valeriana walichii were found to have antileishmanial activity. Bioassay-guided fractionation lead to a caffeic acid bornyl ester of high activity combined with cytotoxicity. The synthesis of a small library of systematically varied compounds result in drugs which were able to cure mice infected with either Leishmania major or Leishmania donovani.[[ii]]
The macrophage infectivity protein (Mip) is a virulence factor of gram-negative bacteria, such as Legionalla, Burkholderia, Francisella, and Yersinia which is often involved in the penetration and/or dissemination of these bacteria. The Mip consist of a peptidyl-proplyl-isomerase whose inhibition result in a reduced cell death in e.g. Burkholderia infected macrophages. Pipecolic esters were found to be potent inhibitors which could be optimized by means of synthesis, X-ray analysis of the ligand-bound Mip and molecular modelling.[[iii]] The compounds show low or none cytotoxicity, fulfill the “Lipinski Rule of Five”, and are, thus, tested in vivo currently.