A gamma-lactone form nafuredin, nafuredin-gamma, also inhibits helminth complex I.
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.
Shiomi
Kazuro
K
School of Pharmaceutical Sciences, Kitasato University, Minato-ku, Tokyo 108-8641, Japan. shiomik@pharm.kitasato-u.ac.jp
Ui
Hideaki
H
Suzuki
Hideaki
H
Hatano
Hiroko
H
Nagamitsu
Tohru
T
Takano
Daisuke
D
Miyadera
Hiroko
H
Yamashita
Tetsuo
T
Kita
Kiyoshi
K
Miyoshi
Hideto
H
Harder
Achim
A
Tomoda
Hiroshi
H
Omura
Satoshi
S
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*
D000871:Anthelmintics; D011753:Pyrones; C423563:nafuredin; D013385:Succinate Dehydrogenase