Microwave assisted synthesis of N-arylphthalamic acids with hyperlipidemic activity.

A series of substituted N-arylphthalamic acids 3a-i has been synthesized by the reaction of phthalic anhydride 1 and aryl- or heterocyclic amines 2a-i, in the absence of solvents, in a domestic microwave oven. The formation of nine N-arylphthalamic acids was accomplished in 1-3 min giving excellent yields for compounds 3a-g, but moderate yield of compounds 3h and 3i, respectively. Compounds 3h and 3i are new. Interestingly, N-arylphthalamic acids 3a-i induced hyperlipidemia in Swiss white mice and also increased animals' body weight.

An evaluation of the marmoset Callithrix jacchus (sagüi) as an experimental model for the dyslipoproteinemia of human Schistosomiasis mansoni.

Human infection with the parasite Schistosoma mansoni is a relatively common occurrence in regions of South America and is associated with liver dysfunction and dyslipoproteinemia. Specifically, the activity of plasma lecithin:cholesterol acyltransferase (LCAT) activity is reduced, the concentration of plasma cholesterol esters falls, phospholipid concentrations are elevated and erythrocyte membranes become cholesterol enriched. Previous studies have utilized rodents (rats and mice) as experimental models to study the dyslipoproteinemia induced by S. mansoni infection. However, the plasma lipoprotein profiles in these animals is very different from humans and infection is not accompanied by decreases in LCAT activity or cholesterol enrichment of their erythrocyte membranes. Here we have evaluated the suitability of the marmoset Callithrix jacchus (sagüi) which is small and readily available in Brazil, as a potential animal model for the study of the dyslipoproteinemia of S. mansoni infections. The plasma lipoprotein compositions and distributions in sagüi, unlike rats or mice, approximate those of man with the LDL representing a major lipoprotein species. The molecular species of phospholipids, cholesterol esters and triglycerides present in sagüi plasma are also very similar to man, whereas those of rats and mice favor the longer chain more unsaturated species, Sagüi, like rodents, can be successfully infected with S. mansoni and after 60 days, this results in a 50% reduction in plasma LCAT activity, an 11% reduction in plasma cholesterol esters, an absolute increase of 46% in plasma phospholipids and an 18% increase in the cholesterol content of erythrocyte membranes. These changes are qualitatively and quantitatively very similar to those previously reported following human infections. Based upon these changes, and the observation that the plasma lipoprotein profile of sagüi and human is similar, we conclude that C. jacchus (sagüi) is an appropriate animal model for the study of dyslipoproteinemia associated with S. mansoni infections.