Department of Pharmacy, University of Napoli "Federico II" , Via D. Montesano 49, 80131 Napoli, Italy.
J Nat Prod. 2014 Feb 28;77(2):351-7. doi: 10.1021/np4009514. Epub 2014 Feb 10.
Palytoxin ranks among the most potent marine biotoxins. Its lethality was well known to native Hawaiians that used to smear a "moss" containing the toxin on their spears to cause instant death to their victims. Human intoxications due to exposure to palytoxin and to its many congeners have been reported worldwide. Currently, palytoxins constitute the main threat to public health across the Mediterranean Sea. In the present work we report on the isolation and stereostructural determination of a new palytoxin analogue from a Hawaiian Palythoa tuberculosa sample. This new toxin is a stereoisomer of 42-hydroxypalytoxin isolated from Palythoa toxica. The whole absolute configuration of this latter toxin is also reported in the paper. Interestingly, the two 42-hydroxypalytoxins do not share the same biological activity. The stereoisomer from P. tuberculosa showed cytotoxicity toward skin HaCaT keratinocytes approximately 1 order of magnitude lower than that of 42-hydroxypalytoxin from P. toxica and about 2 orders of magnitude lower than that of palytoxin itself. This finding holds the prospect of interesting structure-activity relationship evaluations in the future.
海兔毒素是最有效的海洋生物毒素之一。它的致命性为曾经使用含有这种毒素的“苔藓”涂抹在他们的矛上来使受害者立即死亡的夏威夷原住民所熟知。由于暴露于海兔毒素及其许多同系物而导致的人类中毒已在全球范围内报道。目前，海兔毒素是整个地中海地区对公众健康的主要威胁。在本工作中，我们报告了从夏威夷 Palythoa tuberculosa 样本中分离和立体结构确定一种新的海兔毒素类似物。这种新毒素是从 Palythoa toxica 中分离出的 42-羟基海兔毒素的立体异构体。本文还报道了后一种毒素的整个绝对构型。有趣的是，这两种 42-羟基海兔毒素没有相同的生物活性。来自 P. tuberculosa 的立体异构体对皮肤 HaCaT 角质形成细胞的细胞毒性比来自 P. toxica 的 42-羟基海兔毒素低约 1 个数量级，比海兔毒素本身低约 2 个数量级。这一发现为未来进行有趣的结构-活性关系评估提供了前景。
