INVITRO ACTIVITIES OF AND MECHANISMS OF RESISTANCE TO ANTIFOL ANTIMALARIAL-DRUGS
INVITRO ACTIVITIES OF AND MECHANISMS OF RESISTANCE TO ANTIFOL ANTIMALARIAL-DRUGS
复制标题
DOI：
10.1128/aac.27.4.525
复制
发表时间：
1985-01-01
影响因子：
4.9
通讯作者：
DESJARDINS, RE
中科院分区：
文献类型：
--
作者：
MILHOUS, WK;WEATHERLY, NF;DESJARDINS, RE
某些干扰叶酸代谢的药物(磺酸、磺胺类和二氢叶酸还原酶抑制剂)在疟疾的化疗和预防中发挥着重要作用。这些药物的活性和作用机制被认为在大多数方面与它们对原核微生物的活性相似。原虫被认为不能利用完整的外源叶酸，被认为依赖于所需叶酸辅助因子的从头合成。目前的调查是为了寻找一种测试恶性疟原虫对抗疟疾药物的体外敏感性的方法，结果表明，早期关于这种生物叶酸代谢的假设是不正确的。4株恶性疟原虫中有3株在不含叶酸和对氨基苯甲酸的培养液中保存成功。叶酸和对氨基苯甲酸对磺胺类和二氢叶酸还原酶抑制剂的抗疟活性有不同程度的拮抗作用。评估体外抗疟疾活性的最佳条件需要准确控制培养基中的这些因素。对抗疟药的耐药性可能涉及与活性叶酸辅助因子从头合成以及以各种形式利用外源完整叶酸的能力有关的多种因素的复合体。
Certain drugs that interfere with folate metabolism (sulfones, sulfonamides and inhibitors of dihydrofolate reductase) play an important role in the chemotherapy and prophylaxis of malaria. The activities and mechanisms of action of these drugs are regarded as similar in most respects to their activities against procaryotic microorganisms. Believed incapable of utilizing intact exogenous folates, plasmodia are regarded as dependent on de novo synthesis of required folate cofactors. The present investigation, conducted in pursuit of a method for testing the in vitro susceptibility of Plasmodium falciparum to antifol antimalarial drugs, produced evidence that earlier assumptions about the folate metabolism of this organism are not correct. Three of 4 isolates of P. falciparum were successfully maintained in a culture medium depelted of folic acid and p-aminobenzoic acid. The antimalarial activities of sulfonamides and dihydrofolate reductase inhibitors were variably antagonized by the presence of folic acid and p-aminobenzoic acid in the culture medium. Optimum conditions for assessment of antifol antimalarial activity in vitro require precise control of these factors in the culture medium. Resistance to antifol antimalarial drugs may involve a complex of factors related to the de novo synthesis of active folate cofactors and the ability to utilize exogenous intact folates in various forms.