Conditional lethality of the diprotic weak bases chloroquine and quinacrine against Cryptococcus neoformans
Conditional lethality of the diprotic weak bases chloroquine and quinacrine against Cryptococcus neoformans
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DOI：
10.1086/315649
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发表时间：
2000-07-01
影响因子：
6.4
通讯作者：
Levitz, SM
中科院分区：
文献类型：
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作者：
Harrison, TS;Griffin, GE;Levitz, SM
10 μ M氯喹可增强巨噬细胞对新型隐球菌的活性，但不直接抑制隐球菌的生长。研究了酸性隐球菌吞噬体中可能存在的较高氯喹浓度的抗真菌活性。大于或等于30 μ M的浓度可抑制隐球菌的生长，大于或等于100 μ M的浓度可杀死真菌，活性依赖于生理温度和pH.z，其活性是氯喹的50倍，低至100 nM的浓度可增强巨噬细胞抗隐球菌活性。Quinacrine在真菌细胞内的液泡系统中浓缩，在细胞内的新生C.中高度浓缩。氯化铵和巴霉素A都能抑制隐球菌的生长，这表明氯喹和奎宁的活性可能部分是由于ph依赖性过程的破坏。这些发现增加了氯喹和奎宁的已知活性谱，这些和相关化合物可能用于治疗隐球菌病。
Chloroquine at 10 mu M enhances the activity of macrophages against Cryptococcus neoformans but does not directly inhibit cryptococcal growth, The antifungal activity of higher chloroquine concentrations likely to be found within the acidic cryptococcal phagosome was tested. Concentrations of greater than or equal to 30 mu M inhibited cryptococcal growth, and there was fungal killing at concentrations of greater than or equal to 100 mu M. Activity was dependent on physiologic temperature and pH.z Quinacrine was 50-fold more active than chloroquine, and concentrations as low as 100 nM enhanced macrophage anticryptococcal activity. Quinacrine was concentrated within a vacuolar system within the fungal cell and highly concentrated within intracellular C. neoformans. Ammonium chloride and bafilomycin A both inhibited cryptococcal growth, suggesting that the activity of chloroquine and quinacrine may in part be due to disruption of pH-dependent processes. These findings add to the known spectrum of activity of chloroquine and quinacrine, These, and related compounds, may have utility for the treatment of cryptococcosis.