title: Paraphaeosphaeride D and berkleasmin F, new circumventors of arbekacin resistance in MRSA, produced by Paraphaeosphaeria sp. TR-022.
abstract: Two new compounds, designated paraphaeosphaeride D (1) and berkleasmin F (2) together with a previously known compound, berkleasmin A (3), isolated from a culture broth of the fungus Paraphaeosphaeria sp. TR-022, proved to be new circumventors of arbekacin (ABK) resistance in methicillin-resistant Staphylococcus aureus (MRSA). The structures of 1 and 2 were elucidated by spectroscopic analyses, including various NMR experiments. All compounds showed 10-100 times ABK circumvention activities using the paper disc method and reduced the MIC values of ABK against MRSA from 16 μg ml(-1) to 4 μg ml(-1) (fourfold) using the agar dilution method. These new compounds might be promising lead compounds for developing circumventors of ABK resistance in MRSA.
authors.affiliation: Department of Drug Discovery Sciences, Graduate School of Infection Control Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Suga
authors.affiliation: Department of Drug Discovery Sciences, Graduate School of Infection Control Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Mayu
authors.initials: M
authors.lastname: Shiina
authors.affiliation: Department of Drug Discovery Sciences, Graduate School of Infection Control Sciences, Kitasato University, Tokyo, Japan.|Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Asami
authors.affiliation: Department of Drug Discovery Sciences, Graduate School of Infection Control Sciences, Kitasato University, Tokyo, Japan.|Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Iwatsuki
authors.affiliation: Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Nonaka
authors.affiliation: Department of Drug Discovery Sciences, Graduate School of Infection Control Sciences, Kitasato University, Tokyo, Japan.|Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Rokuro
authors.initials: R
authors.lastname: Masuma
authors.affiliation: Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Hidehito
authors.initials: H
authors.lastname: Matsui
authors.affiliation: Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hanaki
authors.affiliation: Chemical Research Laboratories, Kyowa Hakko Kirin, Co., Ltd., Shizuoka, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Iwamoto
authors.affiliation: Chemical Research Laboratories, Kyowa Hakko Kirin, Co., Ltd., Shizuoka, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Onodera
authors.affiliation: Department of Drug Discovery Sciences, Graduate School of Infection Control Sciences, Kitasato University, Tokyo, Japan.|Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Kazuro
authors.initials: K
authors.lastname: Shiomi
authors.affiliation: Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ōmura
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001203:Ascomycota / Q000378:metabolism*; D003982:Dibekacin / Q000031:analogs & derivatives / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D007769:Lactams / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D011753:Pyrones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D007769:Lactams; D011753:Pyrones; D012717:Sesquiterpenes; C000618093:berkleasmin A; C000618092:berkleasmin F; C000618091:paraphaeosphaeride D; D003982:Dibekacin; C031986:arbekacin