Synergistic interaction of a chloroquine metabolite with chloroquine against drug-resistant malaria parasites.
Biochem Pharmacol
; 67(7): 1347-53, 2004 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-15013850
ABSTRACT
We have previously shown that structural modification of chlorpromazine to introduce a basic side chain converts this chloroquine (CQ) resistance-reversing agent into a compound that has activity against Plasmodium falciparum in vitro. In an effort to further dissect the structural features that determine quinoline antimalarial activity and drug resistance-reversing activity, we have studied a series of aminoquinolines that are structurally related to CQ. We have analysed their haematin-binding activities, their antimalarial activities and their abilities to synergise the effect of CQ against drug-resistant P. falciparum. We found that a number of the aminoquinolines were able to interact with haematin but showed no or very weak antiparasitic activity. Interestingly, 4-amino-7-chloroquinoline, which is the CQ nucleus without the basic side chain, was able to act as a resistance-reversing agent. These studies point to structural features that may determine the resistance-modulating potential of weakly basic amphipaths. Interestingly, 4-amino-7-chloroquinoline is a metabolic breakdown product of CQ and may contribute to CQ activity against resistant parasites in vivo.
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Base de dados:
MEDLINE
Assunto principal:
Plasmodium falciparum
/
Resistência a Medicamentos
/
Cloroquina
/
Aminoquinolinas
/
Antimaláricos
Limite:
Animals
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article