Sporotrichosis is an emerging mycosis caused by members of the genus Sporothrix. The disease affects humans and animals, particularly cats, which play an important role in zoonotic transmission. Feline sporotrichosis treatment options include itraconazole (ITC), potassium iodide, and amphotericin B, drugs usually associated with deleterious adverse reactions and refractoriness in cats, especially when using ITC. Thus, affordable, nontoxic, and clinically effective anti-Sporothrix agents are needed. Recently, acylhydrazones (AH), molecules targeting vesicular transport and cell cycle progression, exhibited a potent antifungal activity against several fungal species and displayed low toxicity compared to the current drugs. In this work, the AH derivatives D13 and SB-AF-1002 were tested against Sporothrix schenckii and Sporothrix brasiliensis. MICs of 0.12 to 1 μg/ml were observed for both species in vitro. D13 and SB-AF-1002 showed an additive effect with itraconazole. Treatment with D13 promoted yeast disruption with the release of intracellular components, as confirmed by transmission electron microscopy of S. brasiliensis exposed to the AH derivatives. AH-treated cells displayed thickening of the cell wall, discontinuity of the cell membrane, and an intense cytoplasmic degeneration. In a murine model of sporotrichosis, treatment with AH derivatives was more efficient than ITC, the drug of choice for sporotrichosis. Our results expand the antifungal broadness of AH derivatives and suggest that these drugs can be exploited to combat sporotrichosis.

中文翻译：

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酰腙衍生物对孢子丝菌属的抗真菌活性。

孢子丝菌病是由孢子丝菌属成员引起的一种新兴真菌病。这种疾病影响人类和动物，尤其是猫，它们在人畜共患病传播中起着重要作用。猫孢子丝菌病的治疗选择包括伊曲康唑 (ITC)、碘化钾和两性霉素 B，这些药物通常与猫的有害不良反应和难治性有关，尤其是在使用 ITC 时。因此，负担得起、无毒且临床有效的抗孢子丝菌需要代理商。最近，靶向囊泡转运和细胞周期进程的分子酰腙 (AH) 表现出针对多种真菌的有效抗真菌活性，并且与目前的药物相比显示出低毒性。在这项工作中，AH 衍生物 D13 和 SB-AF-1002 针对申克孢子丝菌和巴西孢子丝菌进行了测试。在体外观察到两种物种的 MIC 均为 0.12 至 1 μg/ml 。D13 和 SB-AF-1002 显示出与伊曲康唑的相加效应。用 D13 处理可促进酵母破坏并释放细胞内成分，这已通过巴西葡萄球菌的透射电子显微镜证实接触 AH 衍生物。AH 处理的细胞表现出细胞壁增厚、细胞膜不连续和强烈的细胞质变性。在孢子丝菌病的小鼠模型中，用 AH 衍生物治疗比 ITC 更有效，ITC 是孢子丝菌病的首选药物。我们的结果扩大了 AH 衍生物的抗真菌广度，并表明可以利用这些药物来对抗孢子丝菌病。