Meragelman Tamara L, Willis Richard H, Woldemichael Girma M, Heaton Andrew, Murphy Peter T, Snader Kenneth M, Newman David J, van Soest Rob, Boyd Michael R, Cardellina John H, McKee Tawnya C
Screening Technologies Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Frederick, Maryland, USA.
J Nat Prod. 2007 Jul;70(7):1133-8. doi: 10.1021/np0700974. Epub 2007 Jun 12.
Fractionation of cytotoxic extracts of specimens of a newly described sponge genus, Candidaspongia, has yielded the candidaspongiolides (3), a complex mixture of acyl esters of a macrolide related to tedanolide. The general structure of the candidaspongiolides was determined by analyses of various 2D NMR and MS data sets. The acyl ester components were identified by GC-MS analysis of the derived fatty acid methyl esters. The mixture could be selectively converted to the deacylated macrolide core (4) by enzymolysis with immobilized porcine lipase, with the structure of the candidaspongiolide core then secured by NMR and MS analysis. The candidaspongiolide mixture was potently cytotoxic, exhibiting a mean panel 50% growth inhibition (GI50) of 14 ng/mL in the National Cancer Institute's 60-cell-line in vitro antitumor screen.
对新发现的海绵属——念珠海绵属（Candidaspongia）标本的细胞毒性提取物进行分级分离，得到了念珠海绵内酯（3），这是一种与特达内酯相关的大环内酯的酰基酯的复杂混合物。通过对各种二维核磁共振（2D NMR）和质谱（MS）数据集的分析，确定了念珠海绵内酯的总体结构。通过对衍生的脂肪酸甲酯进行气相色谱-质谱（GC-MS）分析，鉴定了酰基酯成分。通过用固定化猪胰脂肪酶进行酶解，该混合物可以选择性地转化为脱酰基大环内酯核心（4），然后通过核磁共振（NMR）和质谱（MS）分析确定念珠海绵内酯核心的结构。念珠海绵内酯混合物具有很强的细胞毒性，在美国国立癌症研究所的60细胞系体外抗肿瘤筛选中，平均半数生长抑制率（GI50）为14 ng/mL。
