title: Design, synthesis, and biological evaluation of air-stable nafuredin-γ analogs as complex I inhibitors.
abstract: Nafuredin-γ (2), converted from nafuredin (1) under mild basic conditions, demonstrates potent and selective inhibitory activity against helminth complex I. However, 2 is unstable in air because the conjugated dienes are oxygen-labile. To address this, we designed and synthesized air-stable nafuredin-γ analogs. Although the complex I inhibitory activities of all the new nafuredin-γ analogs were lower than that of 2, all were in the high nM range (IC50: 300-820nM).
authors: Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors: Masaki
authors: M
authors: Ohtawa
authors: Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors: Mari
authors: M
authors: Matsunaga
authors: Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors: Keiko
authors: K
authors: Fukunaga
authors: Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors: Risa
authors: R
authors: Shimizu
authors: Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors: Eri
authors: E
authors: Shimizu
authors: Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors: Shiho
authors: S
authors: Arima
authors: Department of Biomedical Chemistry, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors: Junko
authors: J
authors: Ohmori
authors: Department of Biomedical Chemistry, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors: Kiyoshi
authors: K
authors: Kita
authors: Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors: Kazuro
authors: K
authors: Shiomi
authors: Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors: Satoshi
authors: S
authors: Omura
authors: Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan. Electronic address: nagamitsut@pharm.kitasato-u.ac.jp.
authors: Tohru
authors: T
authors: Nagamitsu
mesh_terms: D000388:Air; D015195:Drug Design; D004355:Drug Stability; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D011753:Pyrones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D011753:Pyrones; C423563:nafuredin; D042967:Electron Transport Complex I
keywords: Air-stable analogs; Complex I inhibitor; Nafuredin-γ