New carbazole anti-bacterials

   Department of Chemistry

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  Prof H Hailes, Dr T Sheppard, Prof Sanjib Bhakta  No more applications being accepted  Competition Funded PhD Project (UK Students Only)

About the Project

Background: In 2021, 1.6 million people died from tuberculosis (TB) and a further 10 million are estimated to have developed active TB. However, only a small number of new anti-TB drugs have been released onto the market over the last 40 years. Some Mycobacterium tuberculosis strains, in the meantime, have acquired genetic mutations that render them resistant to most antibiotics. In recent work we have established that the NSAID carprofen can selectively inhibit the growth of M. tuberculosis

Project aims and overview: Building upon the activity of carprofen, a carbazole, in recent work we have designed, synthesised, and evaluated several carbazoles which exhibited improved anti-mycobacterial potencies and selectivities. The aim of this project is to synthesize novel carbazoles, to systematically improve anti-mycobacterial activities, and probe the mode of action.

Initial studies will focus on optimising the synthetic route to a range of carbazoles with a range of substituents attached to the two aromatic rings. Compounds will be screened in vitro to determine anti-mycobacterial activities and establish structure-activity relationships (SARs). In subsequent studies, modifications will be made to the central heterocyclic ring to probe the SAR and potential mode of action. In years 3-4 of the PhD, building upon earlier data, structural modifications to enhance drug-like properties will be investigated. Labelled analogues will also be prepared for mechanism of action studies.

Who we are looking for: For this project we are seeking a talented organic chemist able to design synthesise and characterise new compounds for biological screening. Also, the student will be involved in rationalising bioactivity data with a view to enhancing the potency and drugability of compounds. They will work in an interdisciplinary environment, interacting with researchers working on treatments for M. tuberculosis

Chemistry (6)

Funding Notes

This project is part of the competitive DTP studentship call at UCL. Depending on the qualifications of the applicants, this project may not necessarily lead to a studentship.


A. Maitra, D. Evangelopoulos, A. Chrzastek, L. Martin, A. Hanrath, E. Chapman, H. C. Hailes, M. Lipman, T. McHugh, S. Waddell, S. Bhakta, J. Antimicrob. Chemother, 2020, 75, 3193.