Hypolipidemic arylthioalkanoic acids.

A series of arylthioalkanoic acids related to probucol was studied for hypolipidemic activity. Homologation of the alkyl side chain led to marked changes in the serum cholesterol and serum triglyceride lowering activity in rats with the best combination of properties appearing in compound 7, 2-[3,5-di-tert-butyl-4-hydroxyphenyl)thio]hexanoic acid. Modification of the ring substitution failed to improve the activity despite the empirical observation that lipophilic substitution was necessary. Removal of the phenolic hydroxyl produced compound 23 with properties similar to 7 but of somewhat lower activity. Replacement of the sulfur by oxygen increased the toxicity of the series. Resolution of racemic 7 did not change the activity of the compound. The LD50 in mice of 7 was between 5000 and 10 000 mg/kg and compound 7 has been submitted for human clinical evaluation.

[Phototoxic effect of polycyclic aromatic compounds on human fibroblast cultures]. / Uber die phototoxische Wirkung polyzyklischer Aromaten (PAK) auf menschliche Fibroblasten-Kulturen.

The phototoxic effects of polycyclic aromatic hydrocarbons (PAH) benzo(a)pyrene, benzo(a)anthrazene, indeno(1,2,3-cd)pyrene, fluoranthene and perylene, and their relation to the known carcinogenicity of these compounds was examined with human fibroblastic cultures. Using different light filters it could be demonstrated that phototoxic effects on the cell cultures only occur with wave lengths shorter than 400 nm, that is in the longwave UV-region. With wave lengths longer than 400 nm, that is in the visible region of light, no cytotoxic effects could be detected. Irradiated with long-wave UV, the highly cancerogenic compounds benzo(a)pyrene, and indeno(1,2,3-cd)pyrene proved to be highly cytotoxic, the moderately cancerogenic benzo(a)anthrazene turned out to be distintly cytotoxic, fluoranthene supposed to be not cancerogenic, proved to be only slightly cytotoxic. Perylene that is considered not cancerogenic either, reacted completely indifferent. These results are completely compatible with those obtained earlier with ciliata (unicellular protozoa). They confirm the assumption that the so-called ciliata test (Tetrahymena pyriformis) can be used as a practicable test system to ascertain the carcinogenicity of PAH.