QUANTITATIVE ASSESSMENT OF ANTI-MALARIAL ACTIVITY INVITRO BY A SEMIAUTOMATED MICRODILUTION TECHNIQUE
QUANTITATIVE ASSESSMENT OF ANTI-MALARIAL ACTIVITY INVITRO BY A SEMIAUTOMATED MICRODILUTION TECHNIQUE
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DOI：
10.1128/aac.16.6.710
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发表时间：
1979-01-01
影响因子：
4.9
通讯作者：
CHULAY, JD
中科院分区：
文献类型：
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作者：
DESJARDINS, RE;CANFIELD, CJ;CHULAY, JD
开发了一种快速、半自动微量稀释方法，用于测量潜在抗疟药物对培养的红细胞内无性形式的人类疟疾寄生虫恶性疟原虫的活性。使用微量滴定板制备待测化合物的系列稀释液。从连续储备培养物中获得的寄生虫在这些平板中传代培养 42 小时。寄生虫对放射性标记核酸前体的摄取的抑制作为抗疟活性的指标。氯喹、奎宁和研究新药甲氟喹活性的重复测量结果表明，该方法灵敏且精确。在体外测试了几种其他抗疟药物和感兴趣的化合物，结果与现有的体内数据一致。使用已知对抗疟药物敏感的恶性疟原虫分离株也可以评估每种测试化合物的交叉耐药性潜力。讨论了这种新测试系统在药物开发计划中的应用和期望。
A rapid, semiautomated microdilution method was developed for measuring the activity of potential antimalarial drugs against cultured intraerythrocytic asexual forms of the human malaria parasite Plasmodium falciparum. Microtitration plates were used to prepare serial dilutions of the compounds to be tested. Parasites, obtained from continuous stock cultures, were subcultured in these plates for 42 h. Inhibition of uptake of a radiolabeled nucleic acid precursor by the parasites served as the indicator of antimalarial activity. Results of repeated measurements of activity with chloroquine, quinine, and the investigational new drug mefloquine demonstrated that the method is sensitive and precise. Several additional antimalarial drugs and compounds of interest were tested in vitro, and the results were consistent with available in vivo data. The use of P. falciparum isolates with known susceptibility to antimalarial drugs also permitted evaluation of the cross-resistance potential of each compound tested. The applications and expectations of this new test system within a drug development program are discussed.