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

在大蒜（Allium sativum L.）中含有或衍生的化合物中，已知硫化物（en）基硫化物负责大蒜的大多数生理或中性功能。我们发现二烯丙基三硫醚（DATS）是一种有效的微管蛋白聚合和癌细胞生长抑制剂，也是一种有效的肝脏解毒系统刺激剂。在这里，我们合成了9种具有不同脂肪侧链的三硫化物，并测定了它们的logp（非电离溶质的亲脂性参数）和对癌细胞生长的抑制活性（IC_<50>(_μM)）。这些三硫化物的log P值从最低的二甲基三硫化物的2.72到最高的二戊基三硫化物的7.62不等。9种三硫化物的IC_<50>与logp之间呈抛物线关系，其中二丁基和二丙基化合物的logp约为5，位于抛物线的最低点，表明其效力最大。logp约为4的DATS比logp相似的三硫化二乙酯强得多的原因尚不完全清楚；但这也许可以用亲核取代中二烯丙基化合物较高的反应活性来解释。3-碳链化合物的生长抑制作用较强；但较弱的化合物，如4碳链或5碳链，如果引入双键将其logp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，我们首次发现在大蒜中没有发现的化合物二丁烯基三硫化物是三硫化物中最有效的结构之一。

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.