ABSTRACT
Glycerol derivatives are a class of compounds, which are easy and inexpensive to produce with potent anti-malarial activities against blood stages of Plasmodium falciparum in vitro. In the present study, one of these compounds, termed 1t, which had the lowest IC(50) values, was assessed in a murine malarial model. Nuclear magnetic resonance imaging and Balb/c mice infected with Plasmodium berghei ANKA strain were treated in a 4-day suppressive test. Mice received a once-daily intraperitoneal administration of 50 mg/Kg of the drug for 4 days. Although no parasitaemia clearance was reached, a slower parasite proliferation and a slightly longer survival time compared with the placebo group were observed.
Subject(s)
Amino Alcohols/therapeutic use , Antimalarials/therapeutic use , Malaria/drug therapy , Plasmodium berghei/drug effects , Amino Alcohols/administration & dosage , Amino Alcohols/pharmacology , Animals , Antimalarials/administration & dosage , Antimalarials/pharmacology , Female , Inhibitory Concentration 50 , Injections, Intraperitoneal , Male , Mice , Mice, Inbred BALB C , Parasitemia/drug therapy , Survival AnalysisABSTRACT
The phospholipid metabolism of Plasmodium falciparum-infected erythrocytes has been shown to be an effective pharmacological target for novel chemotherapy. Thirty-seven monoquaternary ammonium derivatives analogous to choline were screened for their potential antiprotozoal activity against P. falciparum and Leishmania braziliensis. Twenty-three compounds inhibited chloroquine resistant and sensitive P. falciparum strains with inhibitory concentrations ranging from 0.001 microM to 47 microM. Among the inhibitors were six compounds with nanomolar activity containing at least one ethyl group in the polar head and a hydrophobic alkyl chain with 10 to 14 methylene groups. Four compounds also exhibited in vitro antileishmanial properties in the micromolar range.