Cytotoxic di(8-quinolyl) disulfides

It has been shown that the nature of the substituent and its position in the quinoline ring markedly affects the antitumor activity and toxicity of di(8-quinolyl) disulfides. The greatest cytotoxicity in the series of methyl derivatives was shown by the 7-, 6-, and 3-isomers towards HT-1080 (human fibrosarcoma) and MG-22A (mouse hepatoma) tumor cells while the 2-methyl derivatives generally have no effect on these cells. High cytotoxicity was also shown (LC₅₀ <1 μg/ml) by other 7-substituted compounds (Cl, PhO, PhS) but they also appear to be highly toxic towards normal NIH 3Y3 mouse embryonic fibroblasts. A similar trend was observed in the series of 5-substituted compounds (NH₂, Cl, OMe, NO₂) which were highly active towards tumor cells but were toxic to normal cells. The best selectivity was found for the 6-substituted quinolines, the 6-methoxy derivative at low concentration brought about the death of tumor cells but appeared much less toxic towards normal fibroblasts (LC₅₀ 100 μg/ml with a corresponding LD₅₀ of 874 mg/kg ). __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 750–754, May 2007.