COMPARISON OF RESPONSES OF DNA TOPOISOMERASE-I FROM CANDIDA-ALBICANS AND HUMAN-CELLS TO 4 NEW AGENTS WHICH STIMULATE TOPOISOMERASE-DEPENDENT DNA NICKING

DNA topoisomerase I is a potential target for therapeutic antifungal a gents predicted to have a fungicidal mode of action. This report descr ibes four agents with varying degrees of selectivity for the fungal to poisomerase I compared to the human enzyme: 5-hydroxy-1H-indole-3-acet ic acid (5-HIAA), quinizarin, dibenzo-p-dioxin-2-carboxylic acid and 7 -amino-3-hydroxy-2-naphthalenesulfonic acid. Taken together with the r esponse 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 selecti ve targeting of the fungal topoisomerase I over its human counterpart.