title: A gamma-lactone form nafuredin, nafuredin-gamma, also inhibits helminth complex I.
abstract: Nafuredin, a delta-lactone antibiotic, is a fungal metabolite showing selective helminth NADH-fumarate reductase inhibition, and whose target had been revealed as complex I. We found that nafuredin is easily converted to nafuredin-gamma by weak alkaline treatment. The structure of nafuredin-gamma was elucidated as a gamma-lactone form of nafuredin with keto-enol tautomerism. Nafuredin-gamma shows similar complex I inhibitory activity as nafuredin, and it also possesses anthelmintic activity in vivo.
authors.affiliation: School of Pharmaceutical Sciences, Kitasato University, Minato-ku, Tokyo 108-8641, Japan. shiomik@pharm.kitasato-u.ac.jp
authors.forename: Kazuro
authors.initials: K
authors.lastname: Shiomi
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ui
authors.forename: Hideaki
authors.initials: H
authors.lastname: Suzuki
authors.forename: Hiroko
authors.initials: H
authors.lastname: Hatano
authors.forename: Tohru
authors.initials: T
authors.lastname: Nagamitsu
authors.forename: Daisuke
authors.initials: D
authors.lastname: Takano
authors.forename: Hiroko
authors.initials: H
authors.lastname: Miyadera
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Yamashita
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kita
authors.forename: Hideto
authors.initials: H
authors.lastname: Miyoshi
authors.forename: Achim
authors.initials: A
authors.lastname: Harder
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tomoda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Omura
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000737:chemistry / Q000494:pharmacology*; D017165:Ascaris suum / Q000187:drug effects*; D011753:Pyrones / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors*
chemical_list: D000871:Anthelmintics; D011753:Pyrones; C423563:nafuredin; D013385:Succinate Dehydrogenase