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The terpenic diamine GIB24 inhibits the growth of Trypanosoma cruzi epimastigotes and intracellular amastigotes, with proteomic analysis of drug-resistant epimastigotes.
Chemico-Biological Interactions ( IF 4.7 ) Pub Date : 2020-08-06 , DOI: 10.1016/j.cbi.2020.109165
Camila Maria Azeredo 1 , Mauricio Frota Saraiva 2 , Maristela Ribeiro de Oliveira 2 , Gisele Barbosa 3 , Mauro Vieira de Almeida 3 , Marcus Vinicius Nora de Souza 4 , Maurilio José Soares 1
Affiliation  

The effect of N-geranyl-ethane-1,2-diamine dihydochloride (GIB24), a synthetic diamine, was assayed against different developmental forms of the parasitic protozoan Trypanosoma cruzi (strain Dm28c). The compound was effective against culture epimastigote forms (IC50/24h = 5.64 μM; SI = 16.4) and intracellular amastigotes (IC50/24h = 12.89 μM; SI = 7.18), as detected by the MTT methodology and by cell counting, respectively. Incubation of epimastigotes for 6h with 6 μM GIB24 (IC50/24h value) resulted in significant dissipation of the mitochondrial membrane potential, prior to permeabilization of the plasma membrane. Rounded epimastigotes with cell size reduction were observed by scanning electron microscopy. These morpho-physiological changes induced by GIB24 suggest an incidental death process. Treatment of infected Vero cells did not prevent the intracellular amastigotes from completing the intracellular cycle. However, there was a decrease in the number of released parasites, increasing the ratio amastigotes/trypomastigotes. Proteomic analysis of 15 μM GIB24 resistant epimastigotes indicated that the compound acts mainly on mitochondrial components involved in the Krebs cycle and in maintaining the oxidative homeostasis of the parasites. Our data suggest that GIB24 is active against the main morphological forms of T. cruzi.



中文翻译:

萜二胺GIB24通过对耐药性附睾的蛋白质组学分析来抑制锥虫锥虫和胞内变形虫的生长。

的效果Ñ -geranyl -乙烷-1,2-二胺dihydochloride(GIB24),合成二胺,进行测定对抗寄生原生动物的不同发育形式的克氏锥虫(株Dm28c)。通过MTT方法和通过细胞计数分别检测到,该化合物有效对抗培养的鞭毛体形式(IC 50 / 24h = 5.64μM ; SI = 16.4)和细胞内变形虫(IC 50 / 24h = 12.89μM ; SI = 7.18)。 。用6μMGIB24(表皮50/ 24h值)导致质膜透化之前线粒体膜电位的显着耗散。通过扫描电子显微镜观察到圆形的前鞭毛体具有减小的细胞大小。由GIB24诱导的这些形态生理变化暗示了偶然的死亡过程。处理被感染的Vero细胞并不能阻止胞内变形虫完成细胞内循环。但是,释放的寄生虫数量有所减少,从而增加了变形虫/锥虫的比率。对15μMGIB24耐药表鞭毛纲进行蛋白质组学分析表明,该化合物主要作用于与克雷布斯循环有关的线粒体成分,并维持寄生虫的氧化稳态。我们的数据表明,GIB24可以对抗主要形态学的GIB24。克氏锥虫

更新日期:2020-08-22
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