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[新型抗寄生虫药物的研究。17. 新型制剂G-1697的合成及其抗棘球蚴活性研究]

[The search for new antiparasitic agents. 17. The synthesis and study of the anti-echinococcal activity of the new preparation G-1697].

作者信息

Mikhaĭlitsyn F S, Kovalenko F P, Kozyreva N P, Dzhabarova V I, Lebedeva M N, Lychko N D, Bulanova T E

出版信息

Med Parazitol (Mosk). 1996 Jul-Sep(3):38-42.

PMID:9036282
Abstract

The paper describes the synthesis of the new agent G-1697 which is 4-[(benzo-2,1,3-thiadiazolyl-4)amino]-5, 6,7,8-tetrahydrobenzothieno [2,3-d] pyrimidine and the results of testing its acute toxicity and antiparasitic activity on a model of Echinococcus multilocularis invasion at the larval stage in cotton rats. The maximum nonlethal dose of G-1697 was 4.0 g/kg for outbred mice of both sexes whose weight was 14-16 g. Adult cotton rats (males) received the agent with their feed in increasing daily doses for 3 weeks continuously on days 8 to 28 after infection. The daily dose of its active ingredient varied from 0.03 to 0.35 g/kg and averaged 0.12 g/kg (the mean total dose per session was 2.47 g/kg). The baseline weight of parasitic larvocysts (PL) per animal averaged 0.28 g at the baseline. In the treated and control rats sacrificed 34 days following infection, the mean mass of PL per animal was 0.95 and 7.51 g, respectively. In the cotton rats treated with G-1697, the suppressed growth index calculated by three parameters (moderate, maximum, and minimum mass of PL in the animals of the comparable groups after treatment with regard to the similar baseline variables) was 90.8, 91.0 and 92.7, respectively, versus the controls. Among all PL found in each animal, its death was approximately 70-90% in the treated rats.

摘要

本文描述了新型药物G - 1697(4 - [(苯并 - 2,1,3 - 噻二唑基 - 4)氨基]-5,6,7,8 - 四氢苯并噻吩并[2,3 - d]嘧啶)的合成,以及在棉鼠幼虫期多房棘球绦虫侵袭模型上对其急性毒性和抗寄生虫活性的测试结果。G - 1697对体重为14 - 16克的雌雄杂种小鼠的最大非致死剂量为4.0克/千克。成年棉鼠(雄性)在感染后第8至28天连续3周以递增的日剂量通过饲料给药。其活性成分的日剂量从0.03克/千克变化到0.35克/千克,平均为0.12克/千克(每次给药的平均总剂量为2.47克/千克)。每只动物寄生幼虫囊(PL)的初始平均重量为0.28克。在感染后34天处死的治疗组和对照组大鼠中,每只动物PL的平均质量分别为0.95克和7.51克。在用G - 1697治疗的棉鼠中,通过三个参数(治疗后可比组动物中PL的中等、最大和最小质量,相对于相似的初始变量)计算的生长抑制指数分别为90.8、91.0和92.7,与对照组相比。在每只动物发现的所有PL中,治疗组大鼠中PL的死亡率约为70 - 90%。

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