Hallock Y F, Cardellina J H, Balaschak M S, Alexander M R, Prather T R, Shoemaker R H, Boyd M R
Division of Cancer Treatment, National Cancer Institute, Frederick, Maryland 21702-1201, USA.
J Nat Prod. 1995 Dec;58(12):1801-7. doi: 10.1021/np50126a001.
Antitumor bioassay-guided fractionation of the organic extract of the marine sponge Cribrochalina vasculum resulted in the isolation of several closely related cytotoxic acetylenic alcohols [1-8], the structures of which were assigned on the basis of chemical and spectral studies. 3-Hydroxyeicos-(4E)-en-1-yne[1], 3-hydroxydocosa-(4E,15Z)-dien-1-yne[2], 3-hydroxy-16-methyleicos-(4E)-en-1-yne[3], 3-hydroxy-19-methyleicos-(4E)-en-1-yne[4], 3-hydroxy-21-methyldocosa-(4E,15Z)-dien-1-yne [5], and 3-hydroxy-14-methyldocosa-(4E)-en-1-yne [6] are enantiomers of known compounds, while 3-hydroxyheneeicos-(4E)-en-1-yne [7] and 5-hydroxy-16-methyleicos-(3Z)-en-1-yne [8] are new metabolites isolated as minor components. The absolute configuration of C-3 in 1-7 and C-5 in 8 has been assigned as S using the modified Mosher's method. Compounds selected from this series showed selective in vitro antitumor activity against the H-522 non-small cell lung line and the IGROV-1 ovarian line. Synthetic racemic 1 demonstrated a modest dose-related therapeutic activity in a preliminary in vivo xenograft assay based on the latter cell line.
对海洋海绵状血管海绵（Cribrochalina vasculum）的有机提取物进行抗肿瘤生物测定指导的分级分离，得到了几种密切相关的细胞毒性炔醇[1 - 8]，其结构是根据化学和光谱研究确定的。3 - 羟基二十碳 -（4E）- 烯 - 1 - 炔[1]、3 - 羟基二十二碳 -（4E，15Z）- 二烯 - 1 - 炔[2]、3 - 羟基 - 16 - 甲基二十碳 -（4E）- 烯 - 1 - 炔[3]、3 - 羟基 - 19 - 甲基二十碳 -（4E）- 烯 - 1 - 炔[4]、3 - 羟基 - 21 - 甲基二十二碳 -（4E，15Z）- 二烯 - 1 - 炔[5]和3 - 羟基 - 14 - 甲基二十二碳 -（4E）- 烯 - 1 - 炔[6]是已知化合物的对映体，而3 - 羟基二十一碳 -（4E）- 烯 - 1 - 炔[7]和5 - 羟基 - 16 - 甲基二十碳 -（3Z）- 烯 - 1 - 炔[8]是作为次要成分分离得到的新代谢产物。使用改良的莫舍尔方法将1 - 7中C - 3的绝对构型和8中C - 5的绝对构型指定为S。从该系列中选择的化合物对H - 522非小细胞肺癌细胞系和IGROV - 1卵巢癌细胞系表现出选择性体外抗肿瘤活性。合成的外消旋体1在基于后者细胞系的初步体内异种移植试验中显示出适度的剂量相关治疗活性。
