Nonylphenolethoxylates as malarial chloroquine resistance reversal agents

被引:13
作者
Crandall, I
Charuk, J
Kain, KC
机构
[1] Univ Toronto, Div Clin Sci, Dept Med, Toronto, ON M5S 1A8, Canada
[2] Univ Toronto, Fac Med, Mol Med Res Ctr, Toronto, ON M5S 1A8, Canada
[3] Toronto Hosp, Trop Dis Unit, Toronto, ON M5T 2S8, Canada
关键词
D O I
10.1128/AAC.44.9.2431-2434.2000
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 mu M), indicating that they possess antimalarial activity, Further, the presence of <10 mu M concentrations of NPEs caused the 50% inhibitory concentrations for chloroquine resistant lines to drop to levels (less than or equal to 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 (similar to 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.
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页码:2431 / 2434
页数:4
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