title: In vitro activity of E1210, a novel antifungal, against clinically important yeasts and molds.
abstract: E1210 is a new antifungal compound with a novel mechanism of action and broad spectrum of antifungal activity. We investigated the in vitro antifungal activities of E1210 compared to those of fluconazole, itraconazole, voriconazole, amphotericin B, and micafungin against clinical fungal isolates. E1210 showed potent activities against most Candida spp. (MIC(90) of ≤0.008 to 0.06 μg/ml), except for Candida krusei (MICs of 2 to >32 μg/ml). E1210 showed equally potent activities against fluconazole-resistant and fluconazole-susceptible Candida strains. E1210 also had potent activities against various filamentous fungi, including Aspergillus fumigatus (MIC(90) of 0.13 μg/ml). E1210 was also active against Fusarium solani and some black molds. Of note, E1210 showed the greatest activities against Pseudallescheria boydii (MICs of 0.03 to 0.13 μg/ml), Scedosporium prolificans (MIC of 0.03 μg/ml), and Paecilomyces lilacinus (MICs of 0.06 μg/ml) among the compounds tested. The antifungal action of E1210 was fungistatic, but E1210 showed no trailing growth of Candida albicans, which has often been observed with fluconazole. In a cytotoxicity assay using human HK-2 cells, E1210 showed toxicity as low as that of fluconazole. Based on these results, E1210 is likely to be a promising antifungal agent for the treatment of invasive fungal infections.
authors.affiliation: Next Generation Systems Core Function Unit, Eisai Product Creation Systems, Eisai Co., Ltd., 5-1-3 Tokodai, Tsukuba, Ibaraki, Japan. m3-miyazaki@hhc.eisai.co.jp
authors.forename: Mamiko
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Takaaki
authors.initials: T
authors.lastname: Horii
authors.forename: Katsura
authors.initials: K
authors.lastname: Hata
authors.forename: Nao-Aki
authors.initials: NA
authors.lastname: Watanabe
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Nakamoto
authors.forename: Keigo
authors.initials: K
authors.lastname: Tanaka
authors.forename: Syuji
authors.initials: S
authors.lastname: Shirotori
authors.forename: Norio
authors.initials: N
authors.lastname: Murai
authors.forename: Satoshi
authors.initials: S
authors.lastname: Inoue
authors.forename: Masayuki
authors.initials: M
authors.lastname: Matsukura
authors.forename: Shinya
authors.initials: S
authors.lastname: Abe
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yoshimatsu
authors.forename: Makoto
authors.initials: M
authors.lastname: Asada
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology* / Q000633:toxicity; D000666:Amphotericin B / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology* / Q000633:toxicity; D001230:Aspergillus / Q000187:drug effects; D002175:Candida / Q000187:drug effects; D002460:Cell Line; D054714:Echinocandins / Q000494:pharmacology; D015725:Fluconazole / Q000494:pharmacology; D005658:Fungi / Q000187:drug effects*; D005670:Fusarium / Q000187:drug effects; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology* / Q000633:toxicity; D017964:Itraconazole / Q000494:pharmacology; D055666:Lipopeptides / Q000494:pharmacology; D000077551:Micafungin; D008826:Microbial Sensitivity Tests; D010143:Paecilomyces / Q000187:drug effects; D011541:Pseudallescheria / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology; D021681:Scedosporium / Q000187:drug effects; D014230:Triazoles / Q000494:pharmacology; D065819:Voriconazole; D015003:Yeasts / Q000187:drug effects*
chemical_list: C570438:APX001A; D000631:Aminopyridines; D000935:Antifungal Agents; D054714:Echinocandins; D007555:Isoxazoles; D055666:Lipopeptides; D011743:Pyrimidines; D014230:Triazoles; D017964:Itraconazole; D000666:Amphotericin B; D015725:Fluconazole; D065819:Voriconazole; D000077551:Micafungin