Design, synthesis, and biological evaluation of air-stable nafuredin-γ analogs as complex I inhibitors
| Autor: | Junko Ohmori, Mari Matsunaga, Risa Shimizu, Keiko Fukunaga, Eri Shimizu, Tohru Nagamitsu, Kiyoshi Kita, Masaki Ohtawa, Satoshi Omura, Kazuro Shiomi, Shiho Arima |
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| Rok vydání: | 2015 |
| Předmět: |
Electron Transport Complex I
Stereochemistry Chemistry Air Organic Chemistry Clinical Biochemistry Pharmaceutical Science Conjugated system Biochemistry Combinatorial chemistry Inhibitory Concentration 50 Drug Stability Design synthesis Pyrones Drug Design Drug Discovery Molecular Medicine Enzyme Inhibitors Molecular Biology IC50 Biological evaluation |
| Zdroj: | Bioorganic & Medicinal Chemistry. 23:932-943 |
| ISSN: | 0968-0896 |
| Popis: | 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: 300–820 nM). |
| Databáze: | OpenAIRE |
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