Pharmacological study of nine antimicrotubular drugs with acrylophenone structure on Triton WR 1339-induced hyperlipidemia in rats.

Nine (amino-methyl)-2 acrylophenone derivatives having in vitro antimicrotubular activities very similar to those of colchicine are tested on Triton WR 1339-induced hyperlipidemia in rats. By producing a disorganization of the microtubular system, these drugs reduce the lipoprotein secretory process from hepatocytes, and more particularly the triglyceride-rich VLDL secretory process, such that the serum triglyceride, cholesterol and phospholipid levels are decreased. On the other hand, HDL-cholesterol and HDL-phospholipids are increased in a significant manner. Other studies show that serum apoprotein B levels are decreased while serum apoprotein A1 levels are increased. These results are interesting since atherogenous risk is now known to be dyslipemia-related, and is not the same according to the fact that lipids are bound to one or another lipoprotein. Among the four most effective compounds (5,7,8 and 9) three of them possess a methoxy group on the aromatic ring, which seems to distinguish that series from the other two.