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Lookup NU author(s): Dr Alistair Brown
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© 2016 American Chemical Society. Novel pyrroles have been designed, synthesized, and evaluated against mycobacterial strains. The pyrroles have originally been designed as hybrids of the antitubercular drugs BM212 (1) and SQ109 (2), which showed common chemical features with very similar topological distribution. A perfect superposition of the structures of 1 and 2 revealed by computational studies suggested the introduction of bulky substituents at the terminal portion of the pyrrole C3 side chain and the removal of the C5 aryl moiety. Five compounds showed high activity toward Mycobacterium tuberculosis, while 9b and 9c were highly active also against multidrug-resistant clinical isolates. Compound 9c showed low eukaryotic cell toxicity, turning out to be an excellent lead candidate for preclinical trials. In addition, four compounds showed potent inhibition (comparable to that of verapamil) toward the whole-cell drug efflux pump activity of mycobacteria, thus turning out to be promising multidrug-resistance-reversing agents.
Author(s): Bhakta S, Scalacci N, Maitra A, Brown AK, Dasugari S, Evangelopoulos D, McHugh TD, Mortazavi PN, Twist A, Petricci E, Manetti F, Castagnolo D
Publication type: Article
Publication status: Published
Journal: Journal of Medicinal Chemistry
Online publication date: 23/02/2016
Acceptance date: 23/02/2016
ISSN (print): 0022-2623
ISSN (electronic): 1520-4804
Publisher: American Chemical Society
PubMed id: 26907951
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