Saquayamycins G鈥揔, Cytotoxic Angucyclines from Streptomyces sp. Including Two Analogues Bearing the Aminosugar Rednose

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• 作者：Khaled A. Shaaban ; Tamer A. Ahmed ; Markos Leggas ; J眉rgen Rohr
• 刊名：Journal of Natural Products
• 出版年：2012
• 出版时间：July 27, 2012
• 年：2012
• 卷：75
• 期：7
• 页码：1383-1392
• 全文大小：573K
• 年卷期：v.75,no.7(July 27, 2012)
• ISSN：1520-6025

文摘

Streptomyces sp. KY40-1, a strain isolated from the Kentucky Appalachian foothills, is the producer of moromycins A (18) and B (19). Further investigations of this strain led to the isolation and structure elucidation of the five new saquayamycins G鈥揔 (1鈥?b>5), along with known compounds. Two of the new compounds bear the unusual aminosugar rednose, which was found here for the first time in angucyclines. The different attachment positions of this aminosugar in these two compounds indicate a high acceptor substrate flexibility of the responsible glycosyl transferase or alternatively the involvement of multiple glycosyl transferases. The cytotoxic activity of the isolated compounds was determined using human prostate cancer (PC-3) and non-small-cell lung cancer (H460) cell lines. Cell viability assays showed that saquayamycins J (4), K (5), A (7), and B (8) were most active in PC3 cells, with saquayamycin B (8) showing the highest activity (GI₅₀ = 0.0075 渭M). The aminosugar-containing saquayamycins H (2) and saquayamycin B (8) showed the highest activity against H460 cells, with a GI₅₀ of 3.3 and 3.9 渭M, respectively. The results presented here provide more insights into the structure鈥揳ctivity relationship of saquayamycins with respect to the nature, number, and linkage of sugar residues.