效力
化学
异恶唑
体外
体内
白色念珠菌
药效团
CYP3A4型
立体化学
新生隐球菌
侧链
抗真菌
生物活性
广谱
药理学
生物化学
微生物学
组合化学
酶
生物
细胞色素P450
有机化学
聚合物
生物技术
作者
Xiaochen Chi,Fei Xie,Liping Li,Hao Yang,Hao Wu,Xianru Li,Guangxin Xia,Lan Yan,Dazhi Zhang,Yuanying Jiang,Tingjunhong Ni
标识
DOI:10.1016/j.bioorg.2023.106572
摘要
As a continuation study, 29 novel triazoles containing benzyloxy phenyl isoxazole side chain were designed and synthesized based on our previous work. The majority of the compounds exhibited high potency in vitro antifungal activities against eight pathogenic fungi. The most active compounds 13, 20 and 27 displayed outstanding antifungal activity with MIC values ranging from <0.008 µg/mL to 1 µg/mL, and showed potent activity against six drug-resistant Candida auris isolates. Growth curve assays further confirmed the high potency of these compounds. Moreover, compounds 13, 20 and 27 showed a potent inhibitory activity on biofilm formation of C. albicans SC5314 and C. neoformans H99. Notably, compound 13 showed no inhibition of human CYP1A2 and low inhibitory activity against CYP2D6 and CYP3A4, suggesting a low risk of drug-drug interactions. With high potency in vitro and in vivo and good safety profiles, compound 13 will be further investigated as a promising candidate.
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