Synthesis and pharmacological evaluation of novel unsubstituted indole-anthraquinone carboxamide derivatives as potent antihyperlipidemic agents.

Five novel derivatives of N-(9,10-dihydro-9,10-dioxoanthracenyl)-1H-indole-2-carboxamide were synthesized and their lipid-lowering effects studied in hyperlipidemic rats. Fusion of the anthraquinone derivatives at high temperature with 5-indole-2-carbonyl chloride, followed by recrystallization from chloroform/methanol gave the desired compounds in excellent yields. Compounds 1 to 5 at a non-toxic dose (1 ml of 57 microM solutions) and bezafibrate as positive control were administered to rats that were hyperlipidemic due to treatment with Triton WR-1339. A decrease in the plasma levels of triglyceride (TG) and low-density lipoprotein-cholesterol (LDL-C) and an increase in the plasma level of high-density lipoprotein-cholesterol (HDL-C) were observed with compounds 1, 3, 4, and 5. Compounds 1, 4, and 5 significantly reduced total cholesterol (TC) levels as well. These compounds may provide agents for targeting dyslipidemia and cardiovascular disease.