Antitumor polyether macrolides: New and hemisynthetic halichondrins from the New Zealand deep-water sponge Lissodendoryx sp.
Antitumor polyether macrolides: New and hemisynthetic halichondrins from the New Zealand deep-water sponge Lissodendoryx sp.
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DOI：
10.1021/jo962231n
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发表时间：
1997-03-21
影响因子：
3.6
通讯作者：
Munro, MHG
中科院分区：
文献类型：
--
作者：
Litaudon, M;Hickford, SJH;Munro, MHG
在我们对新西兰海洋生物群的生物潜力进行调查期间，注意到一种亮黄色海绵Lissodendoryx sp.。1983年在凯库拉半岛外的深水（> 100 m）中通过疏浚采集的（Poecilosclerida目，Myxillidae科）。这种海绵的提取物对小鼠白血病细胞系P388、DNA病毒（单纯疱疹I型）和RNA病毒（脊髓灰质炎疫苗病毒）具有强烈的抑制作用。1985年对该海绵的初步研究证实其活性成分是稳定的，此外，该海绵的粗提物在体内小鼠P388模型中提供了显著的寿命延长（T/C ≥ 250%）。1在最初的研究中获得的一种具有强烈生物活性的化合物，给出的数据非常令人联想到那些发表的软海绵素系列化合物，2，3尽管注意到差异，这表明已经获得了新的软海绵素。随后再提取较大量的海绵（5 kg），得到粗有机提取物（3.8 g），将其进行生物测定-定向层析，得到三种生物活性组分，已知的软海绵素B（1）、高软海绵素B（2）和新的异构体异高软海绵素B（3），以及几种次要组分。初步来文中报告了3的特征。4为了获得更多的这些软海绵素和次要成分，通过在凯库拉拖网捕捞另外200公斤的Lissodendoryx sp.海绵。将该收集物冷冻干燥并研磨（47 kg），并将来自一部分（20 kg）的提取物进行层析，得到前述三种化合物，软海绵素B（1）、高软海绵素B（2）和异高软海绵素B（3），以及去甲软海绵素B（4）和新衍生物5 r9。
During our investigation of the biological potential of the New Zealand marine biota, attention was drawn to a bright yellow sponge Lissodendoryx sp.(family Myxillidae, order Poecilosclerida) collected by dredging from deep water (> 100 m) off the Kaikoura Peninsula in 1983. Extracts from this sponge were strongly inhibitory against the murine leukemia cell line P388, a DNA virus (Herpes simplex Type I), and an RNA virus (Polio vaccine virus). Initial studies on the sponge in 1985 established that the active components were stable, and furthermore, crude extracts of this sponge offered significant extensions of life-span in an in vivo murine P388 model (T/C∼ 250%). 1 One strongly bioactive compound, obtained in the initial studies, gave data very reminiscent of those published for the halichondrin series of compounds, 2, 3 although differences were noted which suggested that a new halichondrin had been obtained. Subsequent reextraction of a larger quantity of the sponge (5 kg) gave a crude organic extract (3.8 g) which was subjected to bioassay-directed chromatography to yield three biologically active components, the known halichondrin B (1), homohalichondrin B (2), and a new isomer isohomohalichondrin B (3), as well as several minor components. The characterization of 3 was reported in a preliminary communication. 4 In order to obtain more of these halichondrins and the minor components, a further 200 kg of the Lissodendoryx sp. sponge was obtained by trawling off Kaikoura. This collection was freeze-dried and ground (47 kg) and the extract from a portion (20 kg) subjected to chromatography to yield the three compounds described previously, halichondrin B (1), homohalichondrin B (2), and isohomohalichondrin B (3), together with norhalichondrin B (4) and the new derivatives 5r9.