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Antimicrobial Agents and Chemotherapy, April 2008, p. 1318-1324, Vol. 52, No. 4
0066-4804/08/$08.00+0     doi:10.1128/AAC.01159-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

In Vitro and In Vivo Antifungal Activities of T-2307, a Novel Arylamidine{triangledown}

Junichi Mitsuyama,* Nobuhiko Nomura, Kyoko Hashimoto, Eio Yamada, Hiroshi Nishikawa, Makoto Kaeriyama, Akiko Kimura, Yozo Todo, and Hirokazu Narita

Research Laboratories, Toyama Chemical Co. Ltd., 2-4-1 Shimookui, Toyama, Japan

Received 3 September 2007/ Returned for modification 14 October 2007/ Accepted 19 January 2008

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 µg/ml), Cryptococcus neoformans (MIC range, 0.0039 to 0.0625 µg/ml), and Aspergillus species (MIC range, 0.0156 to 4 µg/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.

* Corresponding author. Mailing address: Research Laboratories, Toyama Chemical Co. Ltd., 2-4-1 Shimookui, Toyama 930-8508, Japan. Phone: 81-76-431-8268. Fax: 81-76-431-8208. E-mail: Junichi_Mitsuyama{at}toyama-chemical.co.jp

{triangledown} Published ahead of print on 28 January 2008.

Antimicrobial Agents and Chemotherapy, April 2008, p. 1318-1324, Vol. 52, No. 4
0066-4804/08/$08.00+0     doi:10.1128/AAC.01159-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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