Monoquaternary ammonium derivatives inhibit growth of protozoan parasites.
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.
Bahamontes-Rosa
N
N
Department of Parasitology, Institute of Tropical Medicine, University of Tübingen, Wilhelmstrasse 27, D-72074 Tübingen, Germany.
Robin
A
A
Ambrosio
A R
AR
Messias-Reason
I
I
Beitz
E
E
Flitsch
S L
SL
Kun
J F J
JF
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects; D004912:Erythrocytes; D006801:Humans; D019169:Jurkat Cells / Q000187:drug effects; D007892:Leishmania braziliensis / Q000187:drug effects* / Q000254:growth & development; D021261:Parasitic Sensitivity Tests; D010743:Phospholipids / Q000378:metabolism; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*
D000962:Antimalarials; D000981:Antiprotozoal Agents; D010743:Phospholipids; D000644:Quaternary Ammonium Compounds