de Farias Cabral Vitória Pessoa, Rodrigues Daniel Sampaio, do Amaral Valente Sá Lívia Gurgel, Moreira Lara Elloyse Almeida, da Silva Cecília Rocha, de Andrade Neto João Batista, da Costa Érica Rayanne Mota, Ferreira Thais Lima, de Oliveira Leilson Carvalho, de Souza Beatriz Oliveira, Pinheiro Dávylla Rênnia Saldanha, Cavalcanti Bruno Coêlho, Magalhães Islay Lima, de Moraes Manoel Odorico, Nobre Júnior Hélio Vitoriano
School of Pharmacy, Laboratory for Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza 60430-372, CE, Brazil.
Center for Drug Research and Development (NPDM), Federal University of Ceará, Fortaleza 60430-275, CE, Brazil.
Pathogens. 2025 Jun 20;14(7):613. doi: 10.3390/pathogens14070613.
The resistance of to conventional pharmacological treatments has gradually increased. Thus, new therapeutic strategies are needed. Three tricyclic antidepressants (TCAs), amitriptyline (AMT), nortriptyline (NOR), and clomipramine (CLO), stand out with potential in this regard. Thus, the objective of this study was to evaluate the antibacterial activity of TCAs against . The methodology used broth microdilution, checkerboard, flow cytometry, fluorescence microscopy, and scanning electron microscopy (SEM) techniques. The results showed that the minimum inhibitory concentration (MIC) of AMT was 256 µg/mL, while the MIC of NOR was 128 µg/mL, and the MIC of CLO was between 64 and 128 µg/mL. The TCAs exhibited bactericidal activity. In the analysis of the association with oxacillin (OXA), AMT exhibited 75% synergism, while NOR and CLO obtained 62.5%. In combination with vancomycin (VAN), AMT and NOR presented 100% additive interactions, while CLO exhibited 62.5% indifferent interactions. The mechanism of TCAs, isolated and combined with OXA, was associated with a reduction in cell viability, resulting from their action on the bacterial genetic material and generation of oxidative stress. Furthermore, the action of the drugs produced intense morphological changes in the bacterial cells. In conclusion, TCAs are a potential alternative for antistaphylococcal therapy.
对传统药物治疗的耐药性已逐渐增加。因此，需要新的治疗策略。三种三环类抗抑郁药（TCAs），即阿米替林（AMT）、去甲替林（NOR）和氯米帕明（CLO），在这方面具有潜在优势。因此，本研究的目的是评估三环类抗抑郁药对……的抗菌活性。所采用的方法包括肉汤微量稀释法、棋盘法、流式细胞术、荧光显微镜和扫描电子显微镜（SEM）技术。结果表明，AMT的最低抑菌浓度（MIC）为256μg/mL，而NOR的MIC为128μg/mL，CLO的MIC在64至128μg/mL之间。三环类抗抑郁药表现出杀菌活性。在与苯唑西林（OXA）联合分析中，AMT表现出75%的协同作用，而NOR和CLO的协同率为62.5%。与万古霉素（VAN）联合使用时，AMT和NOR呈现100%的相加相互作用，而CLO表现出62.5%的无明显相互作用。三环类抗抑郁药单独使用以及与OXA联合使用的作用机制与细胞活力降低有关，这是由于它们对细菌遗传物质的作用以及氧化应激的产生。此外，药物的作用使细菌细胞产生了强烈的形态变化。总之，三环类抗抑郁药是抗葡萄球菌治疗的一种潜在替代药物。
