Synthesis and antifungal evaluation of chalcone derivatives combined with fluconazole against drug-resistant Candida albicans / 中国药科大学学报

@#Chalcone is a common scaffold in natural products with optimal properties and biological activities.In this study, we designed and prepared eight new coumarin-chalcone derivatives (5a-5h), and confirmed their structures by 1H NMR and 13C NMR. Their in vitro antifungal activity combined with fluconazole (FLC) against drug-resistant Candida albicans was tested by microdilution method.The results indicated that most chalcone derivatives showed good antifungal activity against drug resistant Candida albicans with FLC, particularly with compound 5g displaying better antifungal activity (MIC50 = 5.60 μg/mL) than FLC (MIC50 = 200 μg/mL) when combined with FLC, so, these derivatives could be used as synergists of antifungal drugs.

The establishment of the drug-resistant Candida albicans disseminated infected mice model / 中国比较医学杂志

Objective Establishing the drug?resistant Candida albicans disseminative infected mice model for new drug screening. Methods The disseminative infected mouse model was generated by intravenously injecting a clinical Drug?resistant Candida albicans strain ( CaR) to immunosuppressive ICR mice. The features of model was evaluated by clinical symptom, survival condition, fungal burden in tissue, histopathology, cytokines assay and medication. Results After infected with CaR (0 day), the death of mice started at the first day, though, compared to clinical drug sensitive strain ( CaS) infected group, the difference of mortality rate in 16?day observation period was not significant in two groups (CaR, 90?7%;CaS, 86?2%, P =0?158), mice in CaR group died faster than those in CaS group at the early stage;On the fourth day of infection, Candida albicans could be detected in the different tissues, and we found fungal burden in kidney and brain was a significant difference. The typical granuloma caused by fungal infection was the main histopathological feature observed in the kidney, brain and heart. Cytokines in renal tissue were detected by flow cytometry, The changes of IL?1α,IL?6,TNF?αand IFN?γin kidney were significant. Compared with CaS group, IL?1 and IFN?γ were significantly higher and TNF?αdecreased significantly in CaR group. The mice of groups CaR and CaS were treated with 10 mg/kg fluconazole, the mortality rates were 83?3% and 37?5%, which have a significant difference. Conclusions In this study, we successfully established a drug?resistant Candida albicans disseminative infected mice model which is potential tool for the development of new anti?infectious agent.