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Discovery of quinolone derivatives as antimycobacterial agents
- Source :
- RSC Advances. 11:24095-24115
- Publication Year :
- 2021
- Publisher :
- Royal Society of Chemistry (RSC), 2021.
-
Abstract
- Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (M. tuberculosis), is an important public health issue. Current first-line drugs administered to TB patients have been in use for over 40 years, whereas second-line drugs display strong side effects and poor compliance. Additionally, designing effective regimens to treat patients infected with multi- and extremely-drug-resistant (MDR and XDR) strains of TB is challenging. In this report, we screened our compound library and identified compound 1 with antituberculosis activity and a minimal inhibitory concentration (MIC) against M. tuberculosis of 20 μg mL−1. Structure optimization and the structure–activity relationship of 1 as the lead compound enabled the design and synthesis of a series of quinolone derivatives, 6a1–6a2, 6b1–6b36, 6c1, 6d1–6d14, 7a1–7a2, 7b1–7b2, 7c1, 8a1–8a5, 9a1–9a4 and 10a1–10a6. These compounds were evaluated in vitro for anti-tubercular activity against the M. tuberculosis H37Rv strain. Among them, compounds 6b6, 6b12 and 6b21 exhibited MIC values in the range of 1.2–3 μg mL−1 and showed excellent activity against the tested MDR-TB strain (MIC: 3, 2.9 and 0.9 μg mL−1, respectively). All three compounds were non-toxic toward A549 and Vero cells (>100 and >50 μg mL−1, respectively). In addition, an antibacterial spectrum test carried out using compound 6b21 showed that this compound specifically inhibits M. tuberculosis. These can serve as a new starting point for the development of anti-TB agents with therapeutic potential.
- Subjects :
- Tuberculosis
Antimycobacterial Agents
medicine.drug_class
General Chemical Engineering
Pharmacology
01 natural sciences
Mycobacterium tuberculosis
03 medical and health sciences
Minimum inhibitory concentration
chemistry.chemical_compound
medicine
030304 developmental biology
0303 health sciences
biology
010405 organic chemistry
business.industry
General Chemistry
Quinolone
medicine.disease
biology.organism_classification
In vitro
0104 chemical sciences
chemistry
Vero cell
business
Lead compound
Subjects
Details
- ISSN :
- 20462069
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- RSC Advances
- Accession number :
- edsair.doi.dedup.....30dee745cb8fdbe361e7ba80659c011b