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.
Manal
M
Al-Najdawi
Yusuf
Y
Al-Hiari
Tariq
T
Al-Qirim
Ghassan
G
Shattat
Mohammad
M
Al-Zweri
Ghassan
G
Abu Sheikha
D000577:Amides / Q000737:chemistry*; D000818:Animals; D000880:Anthraquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D000960:Hypolipidemic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D007211:Indoles / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D021241:Spectrometry, Mass, Electrospray Ionization; D014280:Triglycerides / Q000097:blood
D000577:Amides; D000880:Anthraquinones; D000960:Hypolipidemic Agents; D007211:Indoles; D014280:Triglycerides; D002784:Cholesterol