IMycobacterium tuberculosis/I Inhibitors Based on Arylated Quinoline Carboxylic Acid Backbones with Anti-IMtb/I Gyrase Activity

New antitubercular agents with either a novel mode of action or novel mode of inhibition are urgently needed to overcome the threat of drug-resistant tuberculosis (TB). The present study profiles new arylated quinoline carboxylic acids (QCAs) having activity against replicating and non-replicating M...

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Bibliographic Details
Published in:International journal of molecular sciences 2023-07, Vol.24 (14)
Main Authors: Quimque, Mark Tristan J, Go, Adrian D, Lim, Justin Allen K, Vidar, Warren S, Macabeo, Allan Patrick G
Format: Article
Language:English
Subjects:
Amino acids
Antitubercular agents
Chemical properties
Drug resistance in microorganisms
Drug therapy
Quinoline
Tuberculosis
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Summary:New antitubercular agents with either a novel mode of action or novel mode of inhibition are urgently needed to overcome the threat of drug-resistant tuberculosis (TB). The present study profiles new arylated quinoline carboxylic acids (QCAs) having activity against replicating and non-replicating Mycobacterium tuberculosis (Mtb), the causative agent of TB. Thus, the synthesis, characterization, and in vitro screening (MABA and LORA) of 48 QCAs modified with alkyl, aryl, alkoxy, halogens, and nitro groups in the quinoline ring led to the discovery of two QCA derivatives, 7i and 7m, adorned with C-2 2-(naphthalen-2-yl)/C-6 1-butyl and C-2 22-(phenanthren-3-yl)/C-6 isopropyl, respectively, as the best Mtb inhibitors. DNA gyrase inhibition was shown to be exhibited by both, with QCA 7m illustrating better activity up to a 1 μM test concentration. Finally, a docking model for both compounds with Mtb DNA gyrase was developed, and it showed a good correlation with in vitro results.
ISSN:1422-0067
DOI:10.3390/ijms241411632