In this work, we report the antileishmanial activity of 23 compounds based on 2‐pyrazyl and 2‐pyridylhydrazone derivatives. The compounds were tested against the promastigotes of Leishmania amazonensis and L. braziliensis, murine macrophages, and intracellular L. amazonensis amastigotes. The most potent antileishmanial compound was selected for investigation into its mechanism of action. Among the evaluated compounds, five derivatives [(E)‐3‐((2‐(pyridin‐2‐yl)hydrazono)methyl)benzene‐1,2‐diol (2 b), (E)‐4‐((2‐(pyridin‐2‐yl)hydrazono)methyl)benzene‐1,3‐diol (2 c), (E)‐4‐nitro‐2‐((2‐(pyrazin‐2‐yl)hydrazono)methyl)phenol (2 s), (E)‐2‐(2‐(pyridin‐2‐ylmethylene)hydrazinyl)pyrazine (2 u), and (E)‐2‐(2‐((5‐nitrofuran‐2‐yl)methylene)hydrazinyl)pyrazine (2 v)] exhibited significant activity against L. amazonensis amastigote forms, with IC₅₀ values below 20 μm. The majority of the compounds did not show any toxic effect on murine macrophages. Preliminary studies on the mode of action of members of this hydrazine‐derived series indicate that the accumulation of reactive oxygen species (ROS) and disruption of parasite mitochondrial function are important for the pharmacological effect on L. amazonensis promastigotes.

中文翻译：

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2-吡唑基和吡啶并hydr衍生物的合成，生物活性和作用机理，新型抗leishmanial药剂

在这项工作中，我们报告了23种基于2-吡唑基和2-吡啶基hydr衍生物的化合物的抗衰老活性。该化合物对的前鞭毛体进行测试利什曼亚马孙和L. braziliensis，小鼠巨噬细胞，和细胞内亚马逊利什曼原虫无鞭毛体。选择了最有效的抗衰老化合物来研究其作用机理。在评估的化合物中，有五种衍生物[[ E）-3-（（2-（吡啶-2-基）肼基）甲基）苯-1,2-二醇（2 b），（E）-4-（（2 -（吡啶-2-基）肼基）甲基）苯-1,3-二醇（2 c），（E）-4-硝基-2-（（2-（吡嗪-2-基）肼基）甲基）苯酚（2 s），（E）-2-（2-（吡啶-2-基亚甲基）肼基）吡嗪（2 u）和（E）-2-（2-（（（5-硝基呋喃-2-基）亚甲基）肼基）吡嗪（2 v）]表现出显着的活性，以抵制亚马逊L. amaztigote形式，IC ₅₀值低于20μm。大多数化合物对鼠巨噬细胞没有显示任何毒性作用。对该肼衍生物系列成员的作用方式的初步研究表明，活性氧（ROS）的积累和寄生虫线粒体功能的破坏对于对亚马逊L. amazonensis前鞭毛体的药理作用很重要。