Martins Tracy M M, Lião Luciano M, Oliveira Gerlon A R, A Silva Pedro E, Reis Ana J, Neves Yasmin C, Lima Glaura R C C, Gontijo Beatriz S, do Carmo Neto José R, Pereira Jonathas X, Kipnis André, Menegatti Ricardo
Federal University of Pará, Faculty of Medicine, Center for Morphological Studies (NEM-ATM), 68372-040 Altamira, PA, Brazil.
Federal University of Goiás, Institute of Chemistry, Nuclear Magnetic Resonance Laboratory (LabRMN), 74690-900 Goiânia, GO, Brazil.
ACS Omega. 2025 Aug 26;10(35):39875-39883. doi: 10.1021/acsomega.5c04174. eCollection 2025 Sep 9.
Tuberculosis (TB) remains a significant global public health challenge. The novel compound LQFM326 was evaluated for its antimycobacterial activity against seven Mycobacterium species. Minimum inhibitory concentrations (MICs) were determined, revealing values of 15.6 μg/mL against H37Ra and 12.5 μg/mL against clinical strains. The MIC values observed for these reference antimicrobials against H37Ra were 0.25 μg/mL for rifampicin and 0.125 μg/mL for isoniazid. Surface damage to cells was observed scanning electron microscopy (SEM), confirming morphological alterations induced by LQFM326. Cellular viability was assessed using the Live/Dead assay, with a CC of 126.68 ± 42.66 μg/mL. The selectivity index (SI), calculated from MIC and CC values, ranged from 2.03 to 10.13, with values above 10 indicating favorable selectivity. Additionally, synergistic effects were observed when LQFM326 was combined with other antibiotics. These findings highlight LQFM326 as a promising antimycobacterial agent with potential efflux-inhibitory and synergistic properties. Further studies are needed to validate its efficacy across diverse clinical strains and to elucidate its mechanism of action.
结核病仍然是一项重大的全球公共卫生挑战。对新型化合物LQFM326针对七种分枝杆菌属菌种的抗分枝杆菌活性进行了评估。测定了最低抑菌浓度（MIC），结果显示对H37Ra的MIC值为15.6μg/mL，对临床菌株的MIC值为12.5μg/mL。这些参考抗菌药物对H37Ra的MIC值，利福平为0.25μg/mL，异烟肼为0.125μg/mL。通过扫描电子显微镜（SEM）观察到细胞表面损伤，证实了LQFM326诱导的形态学改变。使用活/死检测法评估细胞活力，细胞毒性浓度（CC）为126.68±42.66μg/mL。根据MIC和CC值计算的选择性指数（SI）范围为2.03至10.13，值高于10表明具有良好的选择性。此外，当LQFM326与其他抗生素联合使用时观察到协同效应。这些发现突出了LQFM326作为一种有前景的抗分枝杆菌药物，具有潜在的外排抑制和协同特性。需要进一步研究以验证其对不同临床菌株的疗效并阐明其作用机制。
