Synthesis and pharmacological evaluation of novel substituted and unsubstituted N-(benzoylphenyl)-1H-indole-2-carboxamides as potent antihypertriglyceridemic agents.
ABSTRACT The N-(benzoylphenyl)-1H-indole-2-carboxamide derivatives 1-6 were synthesized, and the lipid-lowering effects of two of these novel compounds were studied using hyperlipidemic rats as an experimental model. Treatment of ethyl-1H-indole-2-carboxylate with aminobenzophenones in the presence of sodium ethoxide and DMF, followed by purification using column chromatography, gave the target compounds in good yields. The tested animals were divided into control, hyperlipidemic, compounds 2-, 3- and bezafibrate-treated groups. At a dose of 15 mg/kg body weight, compounds 2, 3 and bezafibrate significantly reduced the elevated plasma triglyceride levels after 7 and 24 h. Furthermore, the high-density lipoprotein-cholesterol levels were remarkably increased in all treated groups after 7 and 24 h compared to the hyperlipidemic control group. However, only compounds 2- and 3-treated groups obviously showed a significant reduction in plasma total cholesterol levels after 24 h. It is therefore reasonable to assume that 2 and 3 may have a promising potential in the treatment of hyperlipidemia and coronary heart diseases.
- SourceAvailable from: Yusuf Al-Hiari[show abstract] [hide abstract]
ABSTRACT: In the search for new potential antihyperlipidemic agents, the present study focuses on the synthesis of novel N-(benzoylphenyl)-5-substituted-1H-indole-2-carboxamides (compounds 8-12, 15, 16, 18) and investigating their antihyperlipidemic activity using Triton WR-1339-induced hyperlipidemic rats as an experimental model. Hyperlipidemia was developed by intraperitoneal injection of Triton WR-1339 (250 mg/kg body weight). The tested animals were divided into normal control (NCG), hyperlipidemic (HG), compound 8, 9, 15, 16, 18- and bezafibrate treated groups. At a dose of 15 mg/kg body weight, compounds 9, 16, 18 and bezafibrate (100 mg/kg) significantly (p < 0.0001) reduced elevated plasma triglycerides levels after 12 h compared to the hyperlipidemic control group. However, only the group treated with compounds 9, 16 and 18 showed an obviously significant (p < 0.001) reduction in plasma total cholesterol levels after 12 h compared to the hyperlipidemic control group. Moreover, high density lipoprotein-cholesterol levels were significantly (p < 0.0001) increased in all treated groups after 12 h compared to the hyperlipidemic control group, except for compounds 8 and 15 which revealed inactive. It is therefore reasonable to assume that compounds 9, 16 and 18 may have potential in the treatment of hyperlipidemia.Molecules 01/2011; 16(10):8292-304. · 2.43 Impact Factor