Nonylphenolethoxylates as Malarial Chloroquine Resistance Reversal Agents
AUTOR(ES)
Crandall, Ian
FONTE
American Society for Microbiology
RESUMO
Malaria-associated morbidity and mortality are increasing because of widespread resistance to one of the safest and least expensive antimalarials, chloroquine. The availability of an inexpensive agent that is capable of reversing chloroquine resistance would have a major impact on malaria treatment worldwide. The interaction of nonylphenolethoxylates (NPEs, commercially available synthetic surfactants) with drug-resistant Plasmodium falciparum was examined to determine if NPEs inhibited the growth of the parasites and if NPEs could sensitize resistant parasites to chloroquine. NPEs inhibited the development of the parasite when present in the low- to mid-micromolar range (5 to 90 μM), indicating that they possess antimalarial activity. Further, the presence of <10 μM concentrations of NPEs caused the 50% inhibitory concentrations for chloroquine-resistant lines to drop to levels (≤12 nM) observed for sensitive lines and generally considered to be achievable with treatment courses of chloroquine. Long-chain (>30 ethoxylate units) NPEs were found to be most active in P. falciparum, which contrasts with previously observed maximal activity of short-chain (∼9 ethoxylate units) NPEs in multidrug-resistant mammalian cell lines. NPEs may be attractive chloroquine resistance reversal agents since they are inexpensive and may be selectively directed against P. falciparum without inhibiting mammalian tissue P glycoproteins. Antimalarial preparations that include these agents may prolong the effective life span of chloroquine and other antimalarials.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=90081Documentos Relacionados
- Dihydroethanoanthracene Derivatives as In Vitro Malarial Chloroquine Resistance Reversal Agents
- Antimalarial agents: mechanism of chloroquine resistance.
- Structural Analysis of Chloroquine Resistance Reversal by Imipramine Analogs
- Reversal of Chloroquine Resistance in Plasmodium falciparum Using Combinations of Chemosensitizers
- Polymorphism in Plasmodium falciparum Drug Transporter Proteins and Reversal of In Vitro Chloroquine Resistance by a 9,10-Dihydroethanoanthracene Derivative