C2D2 research 1b - Carbon Monoxide-Releasing Molecules as a Dual-Warhead Approach to Antibiotics

Project: Other projectOther internal award

Project Details

Layman's description

Increasingly certain bacteria are developing resistance to antibiotics and there is an urgent need to develop multi-functional drugs that will overcome the resistance of these 'super-bugs'. This project investigates the possibility of using carbon monoxide (CO), delivered in a safe and targeted way through special carrier molecules, as an antibacterial agent alongside conventional antibiotics.

Key findings

FINDINGS/RESULTS

The principal aim of this project was to prepare new carbon monoxide-releasing molecules which may be used as dual-warheads antibiotic agents. A novel iron tricarbonyl scaffold based on the chalcone motif was prepared and fully characterized. In addition the factors affecting the CO-release mechanism for these complexes was investigated with a range of in situ spectroscopic techniques. Although the complexes did not inhibit the growth of E. coli, the development of the new synthetic methods for the preparation of the compounds will significantly aid with the realisation of future generations of carbon monoxide-releasing molecules. For example, it has demonstrated the type of synthetic methods which have the greatest chance of success when attempting to incorporate additional functionality into the iron tricarbonyl scaffold. Such synthetic insight will be crucial when selecting the best antibiotic structures for incorporation in dual-warhead carbon monoxide-releasing molecules. In addition, inactivity against E. coli does not necessarily imply that the molecules prepared in this project will not be successful antibiotics as related studies have shown that activity is strongly bacterium-dependent. Future studies will evaluate the compounds prepared in this study against other bacteria such as Pseudomonas aeruginosa and Staphylococcus aureus.

COLLABORATIONS

No new collaborations have been established on the basis of this work, although it has reinforced the links between Fairlamb and Lynam in Chemistry and Moir in Biology.

STAFF

Dr Nimesh Mistry was employed for three months.

COMMERCIALISATION/TRANSLATION

None as yet.

APPLICATIONS SUBMITTED

None as yet

ARTICLES SUBMITTED

In preparation
StatusFinished
Effective start/end date1/07/1231/03/13