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Studies on the function and metabolism of alk(en)yl polysulfides derived from food.

食品中烷基多硫化物的功能和代谢研究。

基本信息

批准号：
20380080
负责人：
ARIGA Toyohiko
金额：
$ 11.48万
依托单位：
Nihon University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2008
资助国家：
日本
起止时间：
2008 至 2010
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20380080/
关键词：
栄養化学 Garlic Sulfide Cancer Allium garlic diallyl trisulfide leukemia cancer Redox 2D-PAGE

项目摘要

Of the compounds contained in or derived from garlic (Allium sativum L.), alk(en)yl sulfides are known to be responsible for most of the physiological or neutraceutical functions of garlic. We found that diallyl trisulfide (DATS) is a potent inhibitor of tubulin polymerization and cancer cell growth, and an effective stimulator of the hepatic detoxification system. Here, we synthesized 9 trisulfides having different aliphatic side-chains, and determined their log P, a parameter for lipophilicity of un-ionized solutes, and inhibitory activities, IC_<50>(_μM), toward cancer cell growth. The log P values of these trisulfides ranged from the lowest, 2.72, for dimethyl trisulfide, to the highest, 7.62, for dipentyl trisulfide. The relationship between the IC_<50> and log P of the 9 trisulfides was parabolic in nature, in which dibutenyl- and dipropyl- compounds, determined to have a log P of approximately 5, were located at the minimum point of the parabola, indicating the maximum potency. The reason why DATS, having a log P of about 4, was excessively stronger than diethyl trisulfide, with a similar log P, is not fully understood ; but perhaps it can be explained by a higher reactivity of the diallyl compound in nucleophilic substitution. The compounds with 3-carbon chains were stronger in terms of growth inhibition than the others ; but weaker compounds, those with 4- or 5- carbon chains, showed higher activity if a double bond was introduced into them to reduce their log P to the effective range. In this study, we confirmed the superiority of trisulfides with 3-carbon chains, e.g., DATS and dipropyl trisulfide (DPTS). In addition, we observed for the first time that dibutenyl trisulfide, a compound not found in garlic, is one of the potent structures among alk(en)yl trisulfides.

在大蒜（Allium sativum L.）中所含或衍生的化合物中，已知烷（烯）基硫醚负责大蒜的大部分生理或营养功能。我们发现二烯丙基三硫化物（DATS）是一种有效的微管蛋白聚合和癌细胞生长的抑制剂，也是肝脏解毒系统的有效刺激剂。本文合成了9个具有不同脂肪族侧链的三硫醚，测定了它们的log P（非离子化溶质亲脂性参数）和对癌细胞生长的抑制活性IC_<50>（μM）。这些三硫化物的log P值范围从最低的2.72（二甲基三硫）到最高的7.62（二戊基三硫）。9<50>种三硫化物的IC_1和log P之间的关系本质上是抛物线，其中二丁烯基和二丙基化合物的log P约为5，位于抛物线的最小点，表明最大效力。DATS的log P值约为4，比log P值相似的二乙基三硫强得多，其原因尚不完全清楚;但也许可以用二烯丙基化合物在亲核取代中的更高反应性来解释。具有3个碳链的化合物在生长抑制方面比其他化合物更强;但是较弱的化合物，具有4个或5个碳链的化合物，如果引入双键以将其log P降低到有效范围，则表现出更高的活性。在这项研究中，我们证实了具有3个碳链的三硫化物的优越性，例如，DATS和二丙基三硫化物（DPTS）。此外，我们首次观察到，二丁烯基三硫化物，一种在大蒜中没有发现的化合物，是烷（烯）基三硫化物中的有效结构之一。