Abstract:
:The effect of tryptophan-N-formylated gramicidin (NFG) on the growth of Plasmodium berghei in mice was tested in three different experiments. NFG was shown to be capable of inhibiting the growth of the parasite in a dose-dependent way, although its action did not result in elimination of the parasite and was only temporary, preventing mice from early death, presumably due to cerebral malaria, but not from fatal generalized malaria. Intriguingly, a similar observation was made with two other drugs, (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine, an inhibitor of viral and eukaryotic DNA polymerases, and the presumed topoisomerase II inhibitor, a bisquaternary quinolinium salt. A rise in the level of parasitemia after 8 days, despite continued treatment, was not due to parasite-induced reticulocytosis, as demonstrated in experiments in which this condition was induced artificially. NFG was added in the form of lipid vesicles in which the peptide had been incorporated. The inhibitory action of NFG was not modulated by the lipid composition of the vesicles. Control experiments did not demonstrate any toxicity of NFG when it was administered in lipid vesicles. The main observation is that NFG is able to inhibit the growth of a malaria parasite in vivo at concentrations that are well tolerated by the host.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Otten-Kuipers MA,Franssen FF,Nieuwenhuijs H,Overdulve JP,Roelofsen B,Op den Kamp JAdoi
10.1128/AAC.41.8.1778subject
Has Abstractpub_date
1997-08-01 00:00:00pages
1778-82issue
8eissn
0066-4804issn
1098-6596journal_volume
41pub_type
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