School of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming 650500, PR China.
School of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming 650500, PR China.
Bioorg Med Chem Lett. 2022 Feb 15;58:128525. doi: 10.1016/j.bmcl.2022.128525. Epub 2022 Jan 5.
With the widespread use of azole antifungals in the clinic, the drug resistance has been emerging continuously. In this work, we focus on boron trifluoride etherate catalyzed condensation of indole and salicylaldehydes to form bis(indolyl)methanes (BIMs) in high yields, and in vitro antifungal activity against Candida albicans were evaluated. The results showed that most phenol-derived BIMs combined with fluconazole (FLC) exhibited good antifungal activity against sensitive and drug-resistant C. albicans. Further mechanism study demonstrated that BI-10 combined with FLC could inhibit hyphal growth, result in ROS accumulation, and decrease mitochondrial membrane potential (MMP) as well as altering membrane permeability.
随着唑类抗真菌药物在临床上的广泛应用,耐药性不断出现。在这项工作中,我们专注于三氟化硼乙醚催化吲哚和水杨醛缩合形成双(吲哚基)甲烷(BIMs),产率高,并对体外抗白色念珠菌的活性进行了评估。结果表明,大多数酚衍生的 BIMs 与氟康唑(FLC)结合表现出对敏感和耐药白色念珠菌的良好抗真菌活性。进一步的机制研究表明,BI-10 与 FLC 联合使用可以抑制菌丝生长,导致 ROS 积累,并降低线粒体膜电位(MMP)以及改变膜通透性。