Prof. Andreas Hilgeroth, Martin-Luther-Universität Halle-Wittenberg
ESA Patentverwertungsagentur Sachsen-Anhalt GmbH
So far infections caused by MRSA have been treated using an antibiotic of last resort – vancomycin. In the meantime resistance to this antibiotic has also been observed, mainly due to more frequent use. Multiple resistances develop in parallel, which affects the effectiveness of different antibiotics and even classes of antibiotics. Low effectiveness for systemic diseases, a high interaction potential and increasing patient mortality are limiting the application of such special antibiotics significantly. For these reasons and in anticipation of the rising prevalence of MRSA, there is a need to develop and provide new active substances to treat conditions caused by this bacterium.
The invention relates to novel active substances - Trisindolylcycloalkanes and Indolylbenzocarbazoles - the application of which will overcome resistance mechanisms based on genetic variability. These are completely new substances which cannot be classified into existing classes of antibiotics. Their effectiveness is based on a different mode of action which will allow the treatment of infections caused by otherwise resistant pathogens. The newly developed substances selectively inhibit the growth of MRSA at concentrations in the low micro-molar range. This invention allows these novel substances to be produced safely and with high yield in a simple one-pot reaction.
The invented technology gives the opportunity for the development of antibiotics with superior properties to treat infections caused by resistant bacteria. The incidence of MRSA in Germany is around 4 per 100.000 inhabitants.
Proof of concept
El-Sayed M T et al. Novel inhibitors of the methicillin-resistant Staphylococcus aureus (MRSA)-pyruvate kinase, Journal of Enzyme Inhibition and Medicinal Chemistry (2016), 31:6, 1666-1671, DOI: 10.3109/14756366.2015.1118685El-Sayed M T et al. Discovery of bisindolyl-substituted cycloalkane-anellated indoles as novel class of antibacterial agents against S. aureus and MRSA, Bioorganic & Medicinal Chemistry Letters 26 (2016) 218-221