Abstract
GR99060 and GR99062 are representatives of a series of 1,2,4-triazino[5,6-b]indole compounds. This series possessed broad-spectrum antifungal activity in vitro. The MIC ranges of the two compounds were as follows: 0.25 to 4 micrograms/ml for Candida albicans, 0.25 to 16 micrograms/ml for Candida sp., 1 to 8 micrograms/ml for Aspergillus spp., and 0.25 to 16 micrograms/ml for Cryptococcus neoformans. GR99062 was metabolized in vitro by a mouse liver microsomal preparation, while GR99060 was stable. GR99060 was efficacious in a murine model of systemic candidiasis by oral or parenteral administration, although no clear dose-response was achieved, suggesting that other factors adversely affected the compound's in vivo activity.
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