In this study, 2-chloro-1,3-dimethoxy-5-methylbenzene (CDM), a natural product with anti-Candida albicans activity, was discovered from the Hericium erinaceus mycelium. The minimum inhibitory concentration of CDM was 62.5 μg/mL. Moreover, structural analogues of CDM obtained from chemical synthesis were applied to explore the structure–activity relationship (SAR) of CDM against C. albicans. It was found that methoxy groups, halogen atoms (except fluorine atoms), and methoxy-meta-position methyl groups in the structure of CDM were the key active groups. Furthermore, we investigated the anti-C. albicans mechanism of CDM. Experiments suggested that CDM destroyed the cell membrane of C. albicans, including the cytoplasmic membrane and mitochondrial membrane, and caused the accumulation of reactive oxygen species and mitochondrial dysfunction, which ultimately led to apoptosis of C. albicans. In addition, CDM had no toxicity on human normal gastric mucosal epithelial cells exposed to a concentration of 125 μg/mL. Experiments showed that CDM reduced the damage of C. albicans to the visceral tissue of infected mice and improved the survival rate of mice. Our research provides a scientific basis for the discovery of effective and safe anti-C. albicans drugs from H. erinaceus.

中文翻译：

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从猴头菇中分离出的天然化合物 2-Chloro-1,3-dimethoxy-5-methylbenzo 通过破坏膜和引发细胞凋亡来抑制真菌生长

本研究从猴头菇菌丝体中发现了具有抗白色念珠菌活性的天然产物2-氯-1,3-二甲氧基-5-甲基苯（CDM）。CDM的最低抑菌浓度为62.5 μg/mL。此外，从化学合成中获得的 CDM 的结构类似物被用于探索 CDM 对白色念珠菌的构效关系 (SAR) 。发现CDM结构中的甲氧基、卤原子（氟原子除外）和甲氧基间位甲基是关键的活性基团。此外，我们研究了 CDM 的抗白色念珠菌机制。实验表明 CDM 破坏了白色念珠菌的细胞膜, 包括细胞质膜和线粒体膜, 并引起活性氧的积累和线粒体功能障碍, 最终导致白色念珠菌细胞凋亡。此外，CDM 对暴露于 125 μg/mL 浓度的人正常胃黏膜上皮细胞没有毒性。实验表明，CDM降低了白色念珠菌对感染小鼠内脏组织的损伤，提高了小鼠的存活率。我们的研究为从H. erinaceus中发现有效和安全的抗白色念珠菌药物提供了科学依据。