Synthesis and in Vivo Lipid-Lowering Activity of Novel Imidazoles-5-carboxamide Derivatives in Triton-WR-1339-Induced Hyperlipidemic Wistar Rats

A new series of imidazole-5-carboxamide derivatives were prepared and tested for their anti-hyperlipidemic activity in Triton-WR-1339-induced hyperlipidemic Wistar rats. The purpose of this research was to improve benzophenone carboxamides water solubility maintaining at the same time the antihyperl...

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Bibliographic Details
Published in:	Chemical & pharmaceutical bulletin Vol. 66; no. 10; pp. 953 - 958
Main Authors:	Jasim, Suhair H., Sheikha, Ghassan M. Abu, Abuzaid, Haneen M., Al-Qirim, Tariq M., Shattat, Ghassan F., Sabbah, Dima A., Ala, Samah A., Aboumair, Mustafa S., Sweidan, Kamal A., Bkhaitan, Majdi M.
Format:	Journal Article
Language:	English
Published:	Japan The Pharmaceutical Society of Japan 01-10-2018 Pharmaceutical Society of Japan Japan Science and Technology Agency
Subjects:	Animals Atherogenesis Benzophenone Bezafibrate Biological properties Body weight Carbonyls cardiovascular disease Cholesterol Coupling (molecular) Density Derivatives High density lipoprotein Hyperlipidemias - chemically induced Hyperlipidemias - drug therapy hypolipidemic activity Hypolipidemic Agents - chemical synthesis Hypolipidemic Agents - chemistry Hypolipidemic Agents - therapeutic use Imidazole imidazolecarboxamide Imidazoles - chemical synthesis Imidazoles - chemistry Imidazoles - therapeutic use Injection Intubation, Gastrointestinal Levels Lipids Lipids - chemistry Lipoproteins, HDL - blood Low density lipoprotein Male Molecular Structure Pharmacology Phosgene Polyethylene Glycols - administration & dosage Rats Rats, Wistar Rodents Solubility Triton WR-1339 imidazolecarboxamide cardiovascular disease Triton WR-1339 hypolipidemic activity
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Summary:	A new series of imidazole-5-carboxamide derivatives were prepared and tested for their anti-hyperlipidemic activity in Triton-WR-1339-induced hyperlipidemic Wistar rats. The purpose of this research was to improve benzophenone carboxamides water solubility maintaining at the same time the antihyperlipidemic activity. Compounds 4, 6, 10, and 11 were synthesized through a coupling reaction between imidazoles-5-carbonyl chloride and amino benzophenones. The tested animals (n=48) were divided into six groups: the first group (hyperlipidemic control group; HCG) received an intraperitoneal injection (i.p.) of (300 mg/kg) Triton WR-1339. The second group received i.p. injection of Triton WR-1339 followed by an intra-gastric administration of bezafibrate (100 mg/kg) (bezafibrate; BF). The third, fourth, fifth, and sixth groups received i.p. injection of Triton WR-1339 followed by an intra-gastric administration of (30 mg/kg) of compounds 4, 6, 10, and 11, respectively. At a dose of 30 mg/kg body weight compounds 4, 6, 10, and 11 significantly (p<0.0001) decreased the plasma level of triglyceride (TG), low-density lipoprotein (LDL) and total cholesterol (TC) levels after 18 h of treatment. Additionally, compounds 4, 6, 11 and bezafibrate (100 mg/kg) significantly (p<0.0001) increased the plasma level of high-density lipoprotein (HDL) levels, which is known for its preventive role against atherogenesis. These results demonstrate the possibility of pharmacokinetic properties improvement maintaining the biological and pharmacological profile of these compounds.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0009-2363 1347-5223
DOI:	10.1248/cpb.c18-00346