論文 - 詳細
| RRC ID | 74867 |
|---|---|
| 著者 | Awale S, Ueda JY, Athikomkulchai S, Abdelhamed S, Yokoyama S, Saiki I, Miyatake R. |
| タイトル | Antiausterity agents from Uvaria dac and their preferential cytotoxic activity against human pancreatic cancer cell lines in a nutrient-deprived condition. |
| ジャーナル | J Nat Prod |
| Abstract |
Human pancreatic cancer cell lines are known for their inherent tolerance to nutrition starvation, which enables them to survive under a hypovascular (austerity) tumor microenvironment. The search for agents that preferentially retard the survival of cancer cells under low nutrition conditions (antiausterity agent) is a novel approach to anticancer drug discovery. In this study, it was found that a dichloromethane extract of the stem of Uvaria dac preferentially inhibited PANC-1 human pancreatic cancer cells survival under nutrition-deprived conditions at a concentration of 10 μg/mL. Workup of this bioactive extract led to the discovery of (+)-grandifloracin (8) as a potent antiausterity agent as evaluated in a panel of four human pancreatic cancer cell lines, PANC-1 (PC(50), 14.5 μM), PSN-1 (PC(50), 32.6 μM), MIA PaCa-2 (PC(50), 17.5 μM), and KLM-1 (32.7 μM). (+)-Grandifloracin (8) has been isolated from a natural source for the first time. Its absolute stereochemistry was established by single-crystal X-ray crystallography and circular dichroism spectroscopic analysis. In addition to this, seven other new highly oxygenated cyclohexene derivatives, named uvaridacanes A (1) and B (2), uvaridacols A-D (3, 4, 6, 7), and uvaridapoxide A (5), were also isolated and structurally characterized. |
| 巻・号 | 75(6) |
| ページ | 1177-83 |
| 公開日 | 2012-6-22 |
| DOI | 10.1021/np300295h |
| PMID | 22676269 |
| MeSH | Antineoplastic Agents, Phytogenic / chemistry Antineoplastic Agents, Phytogenic / isolation & purification* Antineoplastic Agents, Phytogenic / pharmacology* Bridged-Ring Compounds / chemistry Bridged-Ring Compounds / isolation & purification* Bridged-Ring Compounds / pharmacology* Crystallography, X-Ray Cyclohexenes / chemistry Cyclohexenes / isolation & purification* Cyclohexenes / pharmacology* Drug Screening Assays, Antitumor Humans Nuclear Magnetic Resonance, Biomolecular Pancreatic Neoplasms / drug therapy* Thailand Uvaria |
| IF | 3.782 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Wikipedia |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | PANC-1(RCB2095) MIA Paca2(RCB2094) KLM-1(RCB2138) |