Antifungal properties in a novel series of triazino[5,6-b]indoles.
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.
Kinsman
O S
OS
Department of Chemotherapy, Glaxo Group Research Limited, Greenford, Middlesex, United Kingdom.
Livermore
D G
DG
Smith
C
C
D000818:Animals; D000935:Antifungal Agents / Q000378:metabolism / Q000494:pharmacology*; D001230:Aspergillus / Q000187:drug effects / Q000378:metabolism; D002176:Candida albicans / Q000187:drug effects / Q000378:metabolism; D007211:Indoles / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D051379:Mice; D008826:Microbial Sensitivity Tests; D014227:Triazines / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*
D000935:Antifungal Agents; D007211:Indoles; D014227:Triazines; C082061:GR 99060; C082062:GR 99062