Department of Pharmacy, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, No. 1239 Siping Road, Shanghai 200092, China.
Department of Organic Chemistry, School of Pharmacy, Navy Medical University, PLA, No. 325 Guohe Road, Shanghai 200433, China.
J Med Chem. 2022 Aug 25;65(16):11257-11269. doi: 10.1021/acs.jmedchem.2c00794. Epub 2022 Aug 3.
and can cause fatal invasive infections, especially in immunocompromised patients. However, few antifungal drugs are available to help treat cryptococcosis. In this study, by compound library screening, we presented the first report of hit compound , which had potent and antifungal activity against spp. tests showed that was not cytotoxic and had highly selective and strong antifungal activities against spp. with MIC values less than 1 μg/mL. Synergism of and fluconazole was also observed . The antifungal efficacy of was assessed in a wax moth larval fungal infection model, and treatment with 10 mg/kg caused a significant reduction in fungal burden and significant extension of the survival time. Taken together, our data indicate that the hit compound warrants further investigation as a novel anti- agent.
并且可能导致致命的侵袭性感染,尤其是在免疫功能低下的患者中。然而,可用的抗真菌药物很少,无法帮助治疗隐球菌病。在这项研究中,通过化合物文库筛选,我们首次报道了具有抗真菌活性的有效化合物 ,对 种具有很强的 和 活性。测试表明,化合物 没有细胞毒性,对 种具有高度选择性和强抗真菌活性,MIC 值小于 1 μg/mL。还观察到化合物 与氟康唑的协同作用。在蜡螟幼虫真菌感染模型中评估了化合物 的抗真菌疗效,用 10 mg/kg 治疗可显著降低真菌负荷并显著延长生存时间。总之,我们的数据表明,该有效化合物 值得进一步研究,作为一种新型的抗真菌药物。