Z. Naturforsch.
69c, 21 – 28
(2014)
doi:10.5560/ZNC.2012-0224
Synthesis and Pharmacological Evaluation of Novel Unsubstituted Indole-Anthraquinone Carboxamide Derivatives as Potent Antihyperlipidemic Agents
Manal
AL-Najdawi1,*,
Yusuf
Al-Hiari1,
Tariq
Al-Qirim2,
Ghassan
Shattat2,
Mohammad
Al-Zweri1, and
Ghassan
Abu Sheikha2
1 Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Jordan, Amman 11942, Jordan. Fax: 00962-6-5300250. E-mail:
manalnajdawi@yahoo.com 2 Faculty of Pharmacy, Al-Zaytoonah Private University, Amman 11733, Jordan
*Author for correspondence and reprint requests
Received December 13, 2012 / January 15, 2014 / published online March 12, 2014
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 re-crystallization from chloroform/methanol gave the desired compounds in excellent yields. Compounds 1 to 5 at a non-toxic dose (1 ml of 57 μm 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.
Key words: N-(9,10-Dihydro-9,10-dioxoanthracenyl)-1H-indole-2-carboxamide, High-Density Lipoprotein, Cholesterol Elevation, Triglyceride Reduction