Over the last 30 years, a demand for new antibacterial agents has grown significantly following concerns about antibiotic resistant bacteria (ARB). Among potential antibiotic candidates, organometallic complexes of transition metals, especially N-heterocyclic carbene (NHC) complexes, became promising due to their wide range of biological activity and ease of adjustment through modification of ligands.
In this project, the primary goal is design and synthesis of antibacterial and antiparasitic agents based on NHC complexes as effective and selective inhibitors of enzymes Thioredoxine (TrxR) or Trypanothione (TryR) reductases. In addition, possible modification of ligands and metal system together with evaluation of antibacterial activity will be carried out.
To achieve the maximal effectiveness of synthesized complexes, several metals in low oxidation state with strong affinity to cysteine residues in enzymes, such as Ag(I), Ru(II), Pd(II) and Rh(I), will be used. The next step of project is comparison of their activity against bacterial TrxR or parasitic TryR along with determination of antibacterial activity, which will be done in cooperation with groups of Prof. Brönstrup and Prof. Stadler. In parallel, possible modification of ligands may be made to achieve high stability and activity of agents. Moreover, theoretical studies of complexes based on computational chemistry methods may be performed together with groups of Dr. Raabe and Prof. Jacob. Throughout this project, a variety routinely performed methods will be used. For example, with help of Elemental analysis, NMR- and Mass spectroscopy, conductometry, X-ray crystallography, structural features of compounds will be revealed. For determination of biological activity of complexes, In-vitro enzymatic assays (for determination of enzyme inhibition), antibacterial assays based on micro-well dilution assay and Kirbi-Bauer disk diffusion method are applied.
Name of Doctoral Researcher
Igor Esarev
Name of Supervisor
Ingo Ott
Institute / Department
Institute for Medicinal and Pharmaceutical Chemistry, TU Braunschweig
Contact details
i.esarev@tu-braunschweig.de