RRC ID 47056
Author Mitsuyama J, Nomura N, Hashimoto K, Yamada E, Nishikawa H, Kaeriyama M, Kimura A, Todo Y, Narita H.
Title In vitro and in vivo antifungal activities of T-2307, a novel arylamidine.
Journal Antimicrob. Agents Chemother.
Abstract The in vitro and in vivo antifungal activities of T-2307, a novel arylamidine, were evaluated and compared with those of fluconazole, voriconazole, micafungin, and amphotericin B. T-2307 exhibited broad-spectrum activity against clinically significant pathogens, including Candida species (MIC range, 0.00025 to 0.0078 microg/ml), Cryptococcus neoformans (MIC range, 0.0039 to 0.0625 microg/ml), and Aspergillus species (MIC range, 0.0156 to 4 microg/ml). Furthermore, T-2307 exhibited potent activity against fluconazole-resistant and fluconazole-susceptible-dose-dependent Candida albicans strains as well as against azole-susceptible strains. T-2307 exhibited fungicidal activity against some Candida and Aspergillus species and against Cryptococcus neoformans. In mouse models of disseminated candidiasis, cryptococcosis, and aspergillosis, the 50% effective doses of T-2307 were 0.00755, 0.117, and 0.391 mg.kg(-1).dose(-1), respectively. This agent was considerably more active than micafungin and amphotericin B against candidiasis and than amphotericin B against cryptococcosis, and its activity was comparable to the activities of micafungin and amphotericin B against aspergillosis. The results of preclinical in vitro and in vivo evaluations performed thus far indicate that T-2307 could represent a potent injectable agent for the treatment of candidiasis, cryptococcosis, and aspergillosis.
Volume 52(4)
Pages 1318-24
Published 2008-4
DOI 10.1128/AAC.01159-07
PII AAC.01159-07
PMID 18227186
PMC PMC2292552
MeSH Animals Antifungal Agents / chemistry Antifungal Agents / pharmacology* Antifungal Agents / therapeutic use Aspergillosis / drug therapy Aspergillosis / microbiology Aspergillus fumigatus / drug effects* Benzamidines / chemistry Benzamidines / pharmacology* Benzamidines / therapeutic use Candida albicans / drug effects* Candidiasis / drug therapy Candidiasis / microbiology Cryptococcosis / drug therapy Cryptococcosis / microbiology Cryptococcus neoformans / drug effects* Male Mice Mice, Inbred ICR Microbial Sensitivity Tests Mycoses / drug therapy* Mycoses / microbiology Specific Pathogen-Free Organisms Treatment Outcome
IF 4.256
Times Cited 29
WOS Category PHARMACOLOGY & PHARMACY MICROBIOLOGY
Resource
Pathogenic microorganisms IFM 46895 IFM 49895