Publication
Title
Design, synthesis and antitubercular potency of 4-hydroxyquinolin-2(1H)-ones
Author
Abstract
In this study, a 50-membered library of substituted 4-hydroxyquinolin-2(1H)-ones and two closely related analogues was designed, scored in-silico for drug likeness and subsequently synthesized. Thirteen derivatives, all sharing a common 3-phenyl substituent showed minimal inhibitory concentrations against Mycobacterium tuberculosis H37Ra below 10 mu M and against Mycobacterium bovis AN5A below 15 mu M but were inactive against faster growing mycobacterial species. None of these selected derivatives showed significant acute toxicity against MRC-5 cells or early signs of genotoxicity in the Vitotox (TM) assay at the active concentration range. The structure activity study relation provided some insight in the further favourable substitution pattern at the 4-hydroxyquinolin-2(1H)-one scaffold and finally 6-fluoro-4-hydroxy-3-phenylquinolin-2(1H)-one (38) was selected as the most promising member of the library with a MIC of 3.2 mu M and a CC50 against MRC-5 of 67.4 mu M. (C) 2017 Elsevier Masson SAS. All rights reserved.
Language
English
Source (journal)
European journal of medicinal chemistry. - Paris, 1974, currens
Publication
Paris : 2017
ISSN
0223-5234
DOI
10.1016/J.EJMECH.2017.06.061
Volume/pages
138 (2017) , p. 491-500
ISI
000411297000039
Pubmed ID
28689097
Full text (Publisher's DOI)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
Project info
Elucidating the mechanism of action of octahydrobenzo[j] phenanthridinediones as novel potent antimycobacterial compounds.
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identifier
Creation 07.11.2017
Last edited 09.10.2023
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