Species of the genus Candida, characterized as commensals of the human microbiota, are opportunistic pathogens capable of generating various types of infections with high associated costs. Considering the limited pharmacological arsenal and the emergence of antifungal-resistant strains, the repositioning of drugs is a strategy used to search for new therapeutic alternatives, in which minocycline and doxycycline have been evaluated as potential candidates. Thus, the objective was to evaluate the in vitro antifungal activity of two tetracyclines, minocycline and doxycycline, and their possible mechanism of action against fluconazole-resistant strains of Candida spp. The sensitivity test for antimicrobials was performed using the broth microdilution technique, and the pharmacological interaction with fluconazole was also analysed using the checkerboard method. To analyse the possible mechanisms of action, flow cytometry assays were performed. The minimum inhibitory concentration obtained was 4–427 µg ml−1 for minocycline and 128–512 µg ml−1 for doxycycline, and mostly indifferent and additive interactions with fluconazole were observed. These tetracyclines were found to promote cellular alterations that generated death by apoptosis, with concentration-dependent reactive oxygen species production and reduced cell viability. Therefore, minocycline and doxycycline present themselves as promising study molecules against Candida spp.

中文翻译：

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米诺环素和多西环素对念珠菌菌株作用机制的可能途径分析。对氟康唑耐药

念珠菌属的物种被认为是人类微生物群的共生体，是机会性病原体，能够产生各种类型的感染，且相关成本很高。考虑到有限的药理学库和抗真菌耐药菌株的出现，药物重新定位是寻找新治疗替代方案的策略，其中米诺环素和强力霉素已被评估为潜在候选药物。因此，目的是评估两种四环素（米诺环素和多西环素）的体外抗真菌活性，及其对抗氟康唑耐药念珠菌菌株的可能作用机制种。采用微量肉汤稀释技术进行抗菌药物的敏感性试验，并采用棋盘法分析与氟康唑的药理相互作用。为了分析可能的作用机制，进行了流式细胞术测定。获得的最小抑制浓度对于米诺环素为 4–427 µg ml -1 ，对于多西环素为128–512 µg ml -1，并且观察到与氟康唑的大多数无影响和附加相互作用。这些四环素被发现可促进细胞改变，导致细胞凋亡导致死亡，产生浓度依赖性活性氧并降低细胞活力。因此，米诺环素和多西环素成为对抗念珠菌的有前途的研究分子种。