首页|咔啉类荧光探针的设计、合成和抗真菌作用机制研究

咔啉类荧光探针的设计、合成和抗真菌作用机制研究

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以课题组前期发现的咔啉类抗真菌化合物JYJ-19为先导化合物,设计合成了 3个新型咔啉类荧光探针F1~F3.体外抗真菌活性结果显示,化合物Fl具有中等的抗真菌活性(MIC80=32 μg·mL-1);荧光探针Fl的Stokes位移为70 nm,具有良好的光学性质,可用于荧光成像研究;亚细胞定位实验表明,Fl在真菌细胞的线粒体富集;细胞内活性氧水平测试结果显示,咔啉类化合物JYJ-19作用下细胞内活性氧水平升高.上述结果表明,咔啉类化合物可能通过作用于真菌细胞的线粒体发挥抗真菌作用.
Design,synthesis,and antifungal mechanism of carbaline fluorescent probes
Three carboline fluorescent probes F1-F3 were designed and synthesized,based on lead compound JYJ-19,an antifungal compound discovered previously by our group.The antifungal activity in vitro results showed that compound F1 had moderate antifungal activity(MIC80=32 μg·mL-1).The stokes shift of Fl is 70 nm.The fluorescent probe F1 has good optical properties and can be used for fluorescence imaging research.Subcellular localization experiments results showed that F1 was enriched in the mitochondria of fungal cells.The detection of intracellular reactive oxygen species levels shows that JYJ-19 enhances intracellular reactive oxygen species levels.The above results indicated that carboline compounds could exert antifungal effects by acting on fungal mitochondria.

carboline compoundCryptococcus neoformansfluorescence probesubcellular localizationreactive oxygen species

王孝清、杨继、施乔、徐东建、刘娜、盛春泉

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福建中医药大学药学院,福建福州 350122

中国人民解放军海军军医大学药学系,上海 200433

咔啉类化合物 新生隐球菌 荧光探针 亚细胞定位 活性氧

国家自然科学基金上海市教委科研创新计划重大项目

819731752019-01-07-00-07-E00073

2024

药学学报
中国药学会 中国医学科学院药物研究所

药学学报

CSTPCD北大核心
影响因子:1.274
ISSN:0513-4870
年,卷(期):2024.59(3)
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