A series of N-phenyl-2,5-dimethylpyrrole derivatives, designed as hybrids of the antitubercular agents BM212 and SQ109, have been synthesized and evaluated against susceptible and drug-resistant mycobacteria strains. Compound 5d, bearing a cyclohexylmethylene side chain, showed high potency against M. tuberculosis including MDR-TB strains at submicromolar concentrations. The new compound shows bacteriostatic activity and low toxicity and proved to be effective against intracellular mycobacteria too, showing an activity profile similar to isoniazid.
|Number of pages||7|
|Journal||ACS Medicinal Chemistry Letters|
|State||Published - 14 May 2020|
Bibliographical noteFunding Information:
We gratefully acknowledge EPSRC (Global Challenges Competition King’s College London), Global Challenges Research Fund at Birkbeck, University of London and Royal Society (RG160870) for research funding and financial support. MT acknowledge King’s College London for a period of leave. DS acknowledges the South African National Research Foundation-SARChI for financial support. We gratefully acknowledge NC3Rs (National Centre for the Replacement, Refinement and Reduction of Animals in Research, NC/T001240/1) for financial support and Carolyn Lam and Simona di Blasio for their help and training on Galleria mellonella assays. FRP and CMR acknowledge Sao Paulo Research Foundation (FAPESP - grant 2018/00163-0) for financial support.
Copyright © 2019 American Chemical Society.
- antimycobacterial drug
- drug resistance
- intracellular tuberculosis