Fostel J, Montgomery D, Lartey P
Anti-Infective Research Division, Abbott Labs., Abbott Park, IL 60064, USA.
FEMS Microbiol Lett. 1996 May 1;138(2-3):105-11. doi: 10.1111/j.1574-6968.1996.tb08142.x.
DNA topoisomerase I is a potential target for therapeutic antifungal agents predicted to have a fungicidal mode of action. This report describes four agents with varying degrees of selectivity for the fungal topoisomerase I compared to the human enzyme: 5-hydroxy-1H-indole-3-acetic acid (5-HIAA), quinizarin, dibenzo-p-dioxin-2-carboxylic acid and 7-amino-4-hydroxy-2-naphthalenesulfonic acid. Taken together with the response of topoisomerase to camptothecin and aminocatechol, these data suggest that there are sufficient structural differences between the topoisomerase I from Candida albicans and human cells to allow selective targeting of the fungal topoisomerase I over its human counterpart.
DNA拓扑异构酶I是治疗性抗真菌药物的一个潜在靶点，预计这些药物具有杀菌作用模式。本报告描述了四种与人类酶相比对真菌拓扑异构酶I具有不同程度选择性的药物：5-羟基-1H-吲哚-3-乙酸（5-HIAA）、醌茜、二苯并-对-二恶英-2-羧酸和7-氨基-4-羟基-2-萘磺酸。结合拓扑异构酶对喜树碱和氨基儿茶酚的反应，这些数据表明白色念珠菌的拓扑异构酶I与人类细胞的拓扑异构酶I之间存在足够的结构差异，从而能够选择性地靶向真菌拓扑异构酶I而非人类对应的酶。
