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

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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.