A New Class Of Potential Chloroquine Resistance Reversal Agents For Plasmodia: Syntheses And Biological Evaluation 1-[(3’-Diethylaminopropyl)-3-(Substituted Phenylmethylene)-Pyrrolidines

1-[(3’-Diethylaminopropyl)-3-(substitutedphenylmethylene) pyrrolidines] were synthe-sized and evaluated for CQ resistant reversal activity. The compounds of the series elicit better biological response than their phenyl methyl analogues in general. The most active compound 4b has been evaluated in vivo in details and the results are presented. The possible mode of action of the compounds of this series is by inhibition of the enzyme heme oxygenase, thereby increasing the levels of heme and hemozoin, which are lethal to the parasite.

A new look at nonparasitized red cells of malaria-infected monkeys

Many reports have shown that malarial parasites can produce distinct morphological and molecular alterations in the membranes of the parasitized erythrocytes (l-8), but few studies have been carried out on nonparasitized erythrocytes of infected animals (9-11).We report here that the outer leaflet of the membrane bilayer of non parasitized erythrocytes contains significantly larger amounts of aminophospholipids (phosphatidylethanolamine (PE) and phosphatidylserine (PS), than the normal red cell membrane. This alteration in nonparasitized red cells is probably caused by Ca2+ -induced crosslinking of spectrin, and gradually disappears after chloroquine treatment. The external localization of PS in these cells together with defective structure of their cytoskeletal network provide a strong basis for the complications associated with malaria infection like thrombosis, infarction and severe anaemia.