Antibiotic and Anticancer Active Molecules
Development of Broad-spectrum Antibiotics based on Sorangicins and Neosorangicins
This project embarks on the evaluation of novel type of myxobacterial macrolides, for which the trivial name neosorangicins have been coined. These metabolites are accessible by fermentation of a Sorangium strain of the HZI culture collection, and are chemically similar to the sorangicins, which are known to act as RNA polymerase inhibitors and to be devoid of intrinsic toxicity. The neosorangicins seem to possess similar biological properties but are the first derivatives of this type that were shown to affect gram-negative pathogens including Pseudomonas aeruginosa and Acinetobacter baumannii. However, the activities of the natural products are still not as good as compared to those of marketed broad spectrum antibiotics, which will afford their optimization by means of medicinal chemistry.
New Synthetic Epothilone B Analogues with the Ability to Pass the Blood-Brain-Barrier
In light of their powerful antitumor activity, epothilones, a new family of natural products isolated by research groups at the Helmholtz Center for Infection research (HZI), in Braunschweig, Germany, have created a tremendous excitement in the scientific community.
Due to their impressive biological profile, multiple efforts towards the synthesis of epothilones and their analogues appeared in the literature and many companies around the world have started research programs and clinical trials. The first commercial drug based on epothilones (IXEMPRA®) has been released by Food and Drug Administration (FDA) in 2007. In addition, quite a few fully synthetic analogues are still under clinical investigation.
Besides flexible routes to the synthesis of natural occuring epothilones special emphasis is placed on Structure-Activity-Relationships (SAR) and the synthesis of biologically active analogues that pass the Blood-Brain-Barrier (BBB).
