title: Therapeutic efficacy of AS2077715 against experimental tinea pedis in guinea pigs in comparison with terbinafine.
abstract: AS2077715 is a novel antifungal metabolite produced by the newly isolated fungal strain Capnodium sp. 339855. This compound has potent inhibitory activity against Trichophyton mentagrophytes mitochondrial cytochrome bc1 complex (complex III) and potent fungicidal activity against T. mentagrophytes, as measured in vitro. Here, we compared the effects of AS2077715 and terbinafine in a guinea pig model of tinea pedis. In a treatment regimen started from the day 7 after infection, 10 daily oral doses of 10 and 20 mg kg(-1) AS2077715 and 20 mg kg(-1) of terbinafine significantly decreased fungal colony-forming units (CFUs) in foot pad skin. In a treatment regimen started from the day 11 after infection, 20 mg kg(-1) AS2077715 significantly reduced fungal CFUs in foot pad skin after 7 daily doses in comparison with 20 mg kg(-1) terbinafine-treated guinea pigs. Our findings suggest that in vivo potency and efficacy of AS2077715 are equal to or greater than that of terbinafine, positioning AS2077715 as a good candidate for use in treating trichophytosis.
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc., Ibaraki, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ohsumi
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc., Ibaraki, Japan.
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Murai
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc., Ibaraki, Japan.
authors.forename: Ikko
authors.initials: I
authors.lastname: Nakamura
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc., Ibaraki, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc., Ibaraki, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Fujie
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006168:Guinea Pigs; D008297:Male; D009281:Naphthalenes / Q000627:therapeutic use*; D012867:Skin / Q000382:microbiology; D000077291:Terbinafine; D014008:Tinea Pedis / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D000077291:Terbinafine