biostudies-literatureLiu KLFundamental Research Funds for the Central UniversitiesWest China Hospital, Sichuan UniversityNational Natural Science Foundation of China24095-24115https://www.ebi.ac.uk/biostudies/studies/S-EPMC9036655biostudies-literatureUnknown11(39)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^-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 <i>in vitro</i> for anti-tubercular activity against the <i>M. tuberculosis</i> 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 <i>M. tuberculosis</i>. These can serve as a new starting point for the development of anti-TB agents with therapeutic potential.RSC advancesDiscovery of quinolone derivatives as antimycobacterial agents.PMC90366552018HXBH036817035702019SCU12029Li XXiong LLiu KLYu LTTeng FGao CfalseDiscovery of quinolone derivatives as antimycobacterial agents.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^-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 <i>in vitro</i> for anti-tubercular activity against the <i>M. tuberculosis</i> 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 <i>M. tuberculosis</i>. These can serve as a new starting point for the development of anti-TB agents with therapeutic potential.2021-01-01T00:00:00Z2021 Jul2026-05-30T15:48:24.74Z2025-04-04T10:02:31.887ZS-EPMC90366553547902010.1039/d0ra09250a