Synthesis, hypolipidemic, and anti- inflammatory activities of arylphthalimides

Phthalimide and some N-substituted cyclic imides may be potent hypolipidemic agents, capable of reducing plasma cholesterol, and triglyceride levels. In this work, N-phenylphthalimide (5a), N-(2-nitrophenyl)phthalimide (5b), N-(3-nitrophenyl)phthalimide (5c), N-(4-nitrophenyl)phthalimide (5d), N-(4-bromophenyl)phthalimide (5e), N-(4-amidaphenyl)phthalimide (5f), N-(4-methylthiophenyl)phthalimide (5g), and N-(4-chlorophenyl)phthalimide (5h) were synthesized, and their effects on reducing lipid levels and as acute antiinflammatory agents in 3-month-old male Swiss mice were compared with phthalimide. To access their safety, the drugs were administered to determine the acute toxicity (LD50 value). In addition, the acute anti-inflammatory activity was evaluated via carrageenan-induced edema; and the effective dose was determined for compounds that showed the best anti-inflammatory activity in comparison with ibuprofen. The compound (5g) proved to be a more active hypolipidemic compound than phthalimide, at a dose level of 20 mg kg(-1) day(-1). The derivative (5g) reduced the plasmatic triglycerides and cholesterol levels by 54 and 41 %, respectively, while the percentages of reduction were 43 and 30 %, respectively, with phthalimide. The hypocholesterolemic and hypotriglyceridemic activities of the (5g) derivative were similar to that obtained with the commercially available drug, pravastatin. The anti-inflammatory activity of compound (5b) was similar to ibuprofen and aspirin at 250 mg kg(-1). Taken together, it was demonstrated that the new phthalimide derivatives were able to increase HDL-cholesterol levels, along with reducing the cholesterol and triglyceride levels and carrageenan-induced edema in mice. Therefore, they may offer promise in the future as new hypolipidemic and anti-inflammatory agents.