中国真菌学杂志2025，Vol.20Issue(6)：568-575,8.DOI:10.3969/j.issn.1673-3827.2025.06.002
新型伊曲康唑衍生物的合成及体外抗真菌活性研究
Synthesis and in vitro antifungal activity evaluation of novel itraconazole derivatives
摘要
Abstract
Objective Based on itraconazole as the lead compound,a series of derivatives(6a-6k)were designed and synthesized to identify highly potent,low-toxicity,and selective antifungal candidates through in vitro screening,while investigating their structure-activity relationships(SAR).Methods Using medicinal chemistry optimization strategies,11 novel itraconazole derivatives were designed and synthesized.The in vitro antifungal activity of the target compounds was determined by the microbroth dilution method,while their antifungal spectrum was assessed via spot assay.The inhibitory effects on fungal hyphae formation and biofilm growth were systematically evaluated.Additionally,we employ Swiss ADME tools to predict the pharmacokinetic properties of compounds,thereby conducting a comprehensive assessment of the compounds.Results All target compounds exhibited significant antifungal activity.Notably,compounds 6c and 6f demonstrated the most potent efficacy,with MIC80 values as low as 0.0156 μg/mL against multiple pathogenic fungi.Importantly,compound 6c also exhibited strong inhibitory activity against drug-resistant strains(MIC80=0.25 μg/mL).At a concentration of 0.0625 μg/mL,compound 6c effectively suppressed hyphae formation in Candida albicans(SC5314).In addition,at the concentration of 0.25 μg/mL,compound 6c has a significant effect on both early and mature biofilm formation.Conclusion Compound 6c exhibits broad-spectrum antifungal activity,including potent inhibition against drug-resistant strains,while also inhibiting hyphae and biofilm formation.It holds potential for further investigation as a candidate antifungal drug molecule.关键词
氮唑/合成/抗真菌/菌丝/生物被膜Key words
azole/synthesis/antifungal/hyphae/biofilm引用本文复制引用
赵萌萌,方文捷,柴晓云,潘炜华,廖万清,王培培..新型伊曲康唑衍生物的合成及体外抗真菌活性研究[J].中国真菌学杂志,2025,20(6):568-575,8.基金项目
临港新片区海洋生物医药科技创新型平台科创基金(RWS-2024-002) （RWS-2024-002）
