{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Liu KL"],"funding":["Fundamental Research Funds for the Central Universities","West China Hospital, Sichuan University","National Natural Science Foundation of China"],"pagination":["24095-24115"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9036655"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11(39)"],"pubmed_abstract":["Tuberculosis (TB), an infectious disease caused by <i>Mycobacterium tuberculosis</i> (<i>M. tuberculosis</i>), 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 <i>M. tuberculosis</i> of 20 μg mL<sup>-1</sup>. 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 <i>in vitro</i> for anti-tubercular activity against the <i>M. tuberculosis</i> H<sub>37</sub>Rv strain. Among them, compounds 6b6, 6b12 and 6b21 exhibited MIC values in the range of 1.2-3 μg mL<sup>-1</sup> and showed excellent activity against the tested MDR-TB strain (MIC: 3, 2.9 and 0.9 μg mL<sup>-1</sup>, respectively). All three compounds were non-toxic toward A549 and Vero cells (>100 and >50 μg mL<sup>-1</sup>, respectively). In addition, an antibacterial spectrum test carried out using compound 6b21 showed that this compound specifically inhibits <i>M. tuberculosis</i>. These can serve as a new starting point for the development of anti-TB agents with therapeutic potential."],"journal":["RSC advances"],"pubmed_title":["Discovery of quinolone derivatives as antimycobacterial agents."],"pmcid":["PMC9036655"],"funding_grant_id":["2018HXBH036","81703570","2019SCU12029"],"pubmed_authors":["Li X","Xiong L","Liu KL","Yu LT","Teng F","Gao C"],"additional_accession":[]},"is_claimable":false,"name":"Discovery of quinolone derivatives as antimycobacterial agents.","description":"Tuberculosis (TB), an infectious disease caused by <i>Mycobacterium tuberculosis</i> (<i>M. tuberculosis</i>), 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 <i>M. tuberculosis</i> of 20 μg mL<sup>-1</sup>. 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 <i>in vitro</i> for anti-tubercular activity against the <i>M. tuberculosis</i> H<sub>37</sub>Rv strain. Among them, compounds 6b6, 6b12 and 6b21 exhibited MIC values in the range of 1.2-3 μg mL<sup>-1</sup> and showed excellent activity against the tested MDR-TB strain (MIC: 3, 2.9 and 0.9 μg mL<sup>-1</sup>, respectively). All three compounds were non-toxic toward A549 and Vero cells (>100 and >50 μg mL<sup>-1</sup>, respectively). In addition, an antibacterial spectrum test carried out using compound 6b21 showed that this compound specifically inhibits <i>M. tuberculosis</i>. These can serve as a new starting point for the development of anti-TB agents with therapeutic potential.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Jul","modification":"2026-05-30T15:48:24.74Z","creation":"2025-04-04T10:02:31.887Z"},"accession":"S-EPMC9036655","cross_references":{"pubmed":["35479020"],"doi":["10.1039/d0ra09250a"]}}