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Discovery of 2-aminopyridine Derivatives with Antichagasic and Antileishmanial Activity Using Phenotypic Assays
Letters in Drug Design & Discovery ( IF 1.2 ) Pub Date : 2020-05-31 , DOI: 10.2174/1570180816666191204105232
Daiane Yukie Tezuka 1 , Sergio de Albuquerque 2 , Carlos Alberto Montanari 1 , Andrei Leitão 1
Affiliation  

Background: Compounds previously studied as anticancer were screened against trypomastigotes to access the bioactivity. The epimastigote form of Trypanosoma cruzi Y strain and the promastigote form of Leishmania amazonensis and Leishmania infantum were used in this work.

Methods: Cell-based assays were performed to access the bioactivity of the compounds using MTT and the flow cytometry methods.

Results: Neq0438, Neq0474 and Neq0440 had the highest potency, with EC50 of 39 μM (L. amazonensis), 52 μM (T. cruzi) and 81 μM (T. cruzi), respectively. These molecules were inactive for Balb/C fibroblast cell line at concentrations above 250 μM, showing selectivity for the parasites.

Conclusion: This is the first report that demonstrates antiparasitic activity for the 2-aminopyridine scaffold, with cross-activity against cancer cells.



中文翻译:

使用表型分析法发现具有抗chagasic和antileishmanial活性的2-氨基吡啶衍生物

背景:筛选了以前研究为抗癌的化合物以对抗锥虫病,以获取其生物活性。本研究使用了克氏锥虫锥虫的副鞭毛形式和亚马逊利什曼原虫和婴儿利什曼原虫的前鞭毛体形式。

方法:使用MTT和流式细胞仪方法进行基于细胞的分析,以获取化合物的生物活性。

结果:Neq0438,Neq0474和Neq0440的效价最高,EC50分别为39μM(亚马逊L. amazonensis),52μM(克鲁斯T. cruzi)和81μM(克鲁斯T. cruzi)。这些分子在浓度超过250μM时对Balb / C成纤维细胞细胞系无活性,显示出对寄生虫的选择性。

结论:这是第一份证明对2-氨基吡啶支架具有抗寄生虫活性并与癌细胞具有交叉活性的报道。

更新日期:2020-05-31
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