咔啉类荧光探针的设计、合成和抗真菌作用机制研究

Design,synthesis,and antifungal mechanism of carbaline fluorescent probes

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F1具有中等的抗真菌活性(MIC80=32μg·mL^(-1));荧光探针F1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,F1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。

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=32μg·mL^(-1)).The stokes shift of F1 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.