Synthesis and pharmacological evaluation of novel substituted and unsubstituted N-(benzoylphenyl)-1H-indole-2-carboxamides as potent antihypertriglyceridemic agents.
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.
Shahwan
Moyad
M
Faculty of Pharmacy, Al-Zaytoonah Private University, Amman 11733, Jordan.
Shattat
Ghassan
G
Al-Qirim
Tariq
T
Sheikha
Ghassan Abu
GA
Al-Hiari
Yusuf
Y
El-Huneidi
Waseem
W
Jarab
Anan
A
Al-Najdawi
Manal
M
D000818:Animals; D001629:Bezafibrate / Q000627:therapeutic use; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D006949:Hyperlipidemias / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D011092:Polyethylene Glycols; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D000960:Hypolipidemic Agents; D014280:Triglycerides; D011092:Polyethylene Glycols; D002784:Cholesterol; C016811:tyloxapol; D001629:Bezafibrate