74(P57) らん藻が生産する新奇な環状ペプチドDendroamideの単離と構造決定およびその抗MDR活性(ポスター発表の部)

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概要

• 論文の詳細を見る

• Tumor cells that survive initial chemotherapy often increase their resistance to not only the original drug but also to other unrelated drugs. The phenomenon, termed multi-drug resistance (MDR), results in the ultimate failure of chemotherapy. Dendroamide A (1), one of three new bistratamide-type cyclic hexapeptides containing thiazole (Tzl) and methyloxazole (mOzl) residues, from the terrestrial blue-green alga Stigonema dendroideum Fremy, exhibits multi-drug-resistance reversing activity. The gross structure of the three compounds, dendroamide A-C (1-3), were determined by NMR and mass spectral analysis. Their absolute stereochemistries were determined by Marfey and chiral GC/MS analysis of derivatives formed from acid hydrolysis of the intact and ozonized peptides. As indicated in Figure 1, dendroamide A was more potent than verapamil in its ability to increase the accumulation of [^3H]vinblastine in P-glycoprotein-overexpressing breast carcinoma (MCF-7/ADR) cells, reaching 〜750% of control at 5μM and maximal effect at 20μM. And as indicated in Figure 2A, MCF-7/ADR cells were killed much more effectively by combinations of daunomycin or actinomycin D and dendroamide A than with identical doses of the drugs alone. Dendroamide A concentrations of 0.6μM or greater increased the sensitivity of MCF-7/ADR cells to vinblastine (Figure 2B) to that of parental MCF-7 cells, indicating that this compound is able to completely overcome P-glycoprotein-mediated MDR in this model system. The abilities of dendroamide A are characteristic of MDR-reversing agents which act as antagonists for drug transport by P-glyciprotein.

• 天然有機化合物討論会の論文
• 1996-09-02

著者

• Smith Charles

  Department Of Pharmacology Fox Chase Cancer Center

• 荻野 純一

  ハワイ大化:(現)東レリサーチセンター

• Moore Richard

  ハワイ大化

• Patterson Gregory

  ハワイ大化

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