A PENTAHALOGENATED MONOTERPENE FROM THE RED ALGA PORTIERIA-HORNEMANNII PRODUCES A NOVEL CYTOTOXICITY PROFILE AGAINST A DIVERSE PANEL OF HUMAN TUMOR-CELL LINES
A PENTAHALOGENATED MONOTERPENE FROM THE RED ALGA PORTIERIA-HORNEMANNII PRODUCES A NOVEL CYTOTOXICITY PROFILE AGAINST A DIVERSE PANEL OF HUMAN TUMOR-CELL LINES
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DOI：
10.1021/jm00094a012
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发表时间：
1992-08-07
影响因子：
7.3
通讯作者：
BOYD, MR
中科院分区：
文献类型：
--
作者：
FULLER, RW;CARDELLINA, JH;BOYD, MR
从红菇Portieria hornemannii的有机提取物中分离得到一种多卤代无环单萜6（R）-溴-3（S）-（溴甲基）-7-甲基-2，3，7-三氯-1-辛烯（1）。X射线衍射分析提供了完整的结构，包括不同卤素原子的正确位置和绝对立体化学的测定。详细的NMR分析提供了完整的H-1和C-13归属。化合物1对美国国家癌症研究所的新的体外人肿瘤细胞系筛选小组表现出高度差异的细胞毒性;脑肿瘤、肾和结肠肿瘤细胞系对1最敏感，而白血病和黑色素瘤细胞系相对较不敏感。第二次收集的P. hornemanni产生了新的单环2，细胞毒性相当小，没有差异活性。基于其在NCI初步筛选中前所未有的细胞毒性特征，化合物1已被NCI决策网络委员会选择用于临床前药物开发。
A polyhalogenated acyclic monoterpene, 6(R)-bromo-3(S)-(bromomethyl)-7-methyl-2,3,7-trichloro-1-octene (1) was obtained as a major component of the organic extract of the red alga Portieria hornemannii. X-ray diffraction analysis provided the complete structure, including correct placement of the different halogen atoms and determination of the absolute stereochemistry. Detailed NMR analyses provided complete H-1 and C-13 assignments. Compound 1 exhibited highly differential cytotoxicity against the U.S. National Cancer Institute's new in vitro human tumor cell line screening panel; brain tumor, renal, and colon tumor cell lines were most sensitive to 1, while leukemia and melanoma lines were relatively less sensitive. A second collection of P. hornemanni yielded the novel, monocyclic 2, considerably less cytotoxic and devoid of differential activity. On the basis of its unprecedented cytotoxicity profile in the NCI primary screen, compound 1 has been selected by the NCI Decision Network Committee for preclinical drug development.