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布氏冈比亚锥虫:二氯二氨铂(II)化合物和降血脂药物对其血液形式体外生长的抑制作用

Trypanosoma brucei gambiense: growth in vitro of bloodstream forms inhibited by dichlorodiammineplatinum (II) compounds and hypolipidemic drugs.

作者信息

Balber A E, Gonias S L, Pizzo S V

出版信息

Exp Parasitol. 1985 Feb;59(1):74-80. doi: 10.1016/0014-4894(85)90059-1.

DOI:10.1016/0014-4894(85)90059-1
PMID:4038488
Abstract

Infectious bloodstream forms of Trypanosoma brucei gambiense were grown in microcultures of murine bone marrow cells in 96-well tissue culture plates. Limiting dilution studies showed that fewer than 10 cultured trypanosomes developed into populations of about 5 X 10(4) parasites per well in a week. Bloodstream parasites were reisolated with high efficiency from mice infected with cultured parasites; fewer than 10 bloodstream parasites successfully established a trypanosome population in a microculture. Both the cis and trans isomers of dichlorodiammineplatinum (II) (cisplatin and transplatin) and a hypolipidemic agent, Wy 14643, were found to have activity against T. b. gambiense growing in microcultures. The minimum concentration of drug necessary to completely eliminate parasites from microcultures was 4 microM for cisplatin, 40 microM for transplatin, and 500 microM for Wy 14643. A preformed complex of cisplatin and bovine serum albumin and another hypolipidemic agent, chlofibric acid, were inactive. This culture system should be useful for rapid screening of large numbers of compounds for trypanocidal activity.

摘要

布氏冈比亚锥虫的感染性血流型在96孔组织培养板中的小鼠骨髓细胞微培养物中生长。有限稀释研究表明,在一周内,每孔中少于10个培养的锥虫发展成约5×10⁴个寄生虫的群体。从感染培养寄生虫的小鼠中高效重新分离出血流寄生虫;少于10个血流寄生虫在微培养中成功建立锥虫群体。发现二氯二氨铂(II)的顺式和反式异构体(顺铂和反铂)以及一种降血脂药物Wy 14643对在微培养中生长的布氏冈比亚锥虫有活性。从微培养物中完全消除寄生虫所需的最低药物浓度,顺铂为4微摩尔,反铂为40微摩尔,Wy 14643为500微摩尔。顺铂与牛血清白蛋白的预制复合物以及另一种降血脂药物氯贝酸无活性。该培养系统应有助于快速筛选大量具有杀锥虫活性的化合物。

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