磺胺类药物对恶性疟原虫二氢蝶酸合酶的抑制作用及其体外生长抑制
Inhibition of Plasmodium falciparum dihydropteroate synthetase and growth in vitro by sulfa drugs.
作者信息
Zhang Y, Meshnick S R
机构信息
Department of Microbiology, City University of New York Medical School, New York 10031.
出版信息
Antimicrob Agents Chemother. 1991 Feb;35(2):267-71. doi: 10.1128/AAC.35.2.267.
Abstract
The Michaelis-Menten inhibitory constants (Kis) and the concentrations required for 50% inhibition of the Plasmodium falciparum dihydropteroate synthetase were determined for six sulfa drugs. These drugs inhibited the in vitro growth of P. falciparum (50% lethal concentration) at concentrations of 30 to 500 nM; these concentrations were 100 to 1,000 times lower than the concentrations required for 50% inhibition and Kis (6 to 500 microM). The uptake of p-aminobenzoic acid was not inhibited by the sulfa drugs. However, infected erythrocytes took up more labeled sulfamethoxazole than did uninfected erythrocytes. Thus, the concentration of sulfa drugs by malaria parasites may explain how sulfa drugs inhibit in vitro growth of parasites through the inhibition of dihydropteroate synthetase.
摘要
测定了六种磺胺类药物的米氏抑制常数（Kis）以及抑制恶性疟原虫二氢蝶酸合酶50%活性所需的浓度。这些药物在30至500 nM的浓度下可抑制恶性疟原虫的体外生长（50%致死浓度）；这些浓度比抑制50%活性所需的浓度和Kis（6至500 microM）低100至1000倍。磺胺类药物不抑制对氨基苯甲酸的摄取。然而，感染疟原虫的红细胞比未感染的红细胞摄取更多标记的磺胺甲恶唑。因此，疟原虫对磺胺类药物的富集可能解释了磺胺类药物如何通过抑制二氢蝶酸合酶来抑制寄生虫的体外生长。
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