Discovery and Development of a New Class of Metal-Based Antibacterial Compound
The worrying appearance of microbial resistance to antibiotics is a worldwide problem which needs to be tackled urgently. Microbial resistance to the common classes of antibiotics involving purely organic compounds unfortunately develops very rapidly and in most cases, resistance was detected soon after or even before release of the antibiotic to the market. Therefore, novel concepts for antibiotics must be investigated, and metal-containing compounds hold particular promise in that area. We discovered a tri-hetero-metallic complex that has potent activity against various pathogenic bacterial strains including methicillin-resistant Staphylococcus aureus (MRSA). A systematic structure–activity relationship (SAR) study was carried out in order to improve the properties of the lead compound. The most potent mono-metallic complex derived from this SAR has an antibacterial activity comparable to the well-established organic drugs amoxicillin and norfloxacin and importantly, only moderate cytotoxicity against mammalian cells. Microbiological studies on membrane potential, membrane permeabilization, and cell wall integrity revealed that the compound targets the bacterial membrane and disturbs cell wall integrity. The design, synthesis and biological evaluation of these novel class of metal-based antibacterial drug candidates will be presented in the first half of the research seminar.
In the second half, I will briefly discuss my future research plans.
1.M. Wenzel§, M. Patra§, C. H. R. Senges, J. J. Stepanek, A. Pinto, P. Prochnow, I. Ott, N. Metzler-Nolte*, J. E. Bandow*, ACS Chem. Biol. 2013, 8, 1442-1450
(§ = co-first authors).
2.M. Patra, M. Wenzel, P. Prochnow, V. Pierroz, G. Gasser, J. E. Bandow* and N. Metzler-Nolte*. Chem. Sci., 2015, 6, 214-224.