Babijczuk Karolina, Wawrzyniak Klaudia, Warżajtis Beata, Rychlewska Urszula, Nowak Damian, da Victoria Banda Yunna, Mrówczyńska Lucyna, Jasiewicz Beata
Department of Bioactive Products, Faculty of Chemistry, Adam Mickiewicz University, Uniwersytetu Poznańskiego 8, 61-614 Poznan, Poland.
Department of Crystallography, Faculty of Chemistry, Adam Mickiewicz University, Uniwersytetu Poznańskiego 8, 61-614 Poznan, Poland.
Int J Mol Sci. 2025 Sep 16;26(18):9018. doi: 10.3390/ijms26189018.
In recent years, we have observed a growing interest in molecular hybridization, which involves combining chemically and pharmacologically diverse fragments into a single molecule. In this study, we designed and synthesized a series of indole-pyrazole hybrids, variously substituted at the pyrazole ring. The compounds were characterized by spectroscopic methods, and the structures of most of them were confirmed by X-ray analysis. Reactions of 3-(dimethylaminomethyl)indole with bromo-methyl-pyrazole derivatives proceeded in a tautomer-selective mode: the 4-bromo-3(5)-methyl-((1-pyrazol-1-yl)methyl)-1-indole tautomers, obtained from the 4-bromo-3-methyl-1-pyrazole, could be isolated by column chromatography. In contrast, the 3-bromo-5-methyl-1-pyrazole yielded the ((5-bromo-3-methyl-1H-pyrazol-1-yl)methyl)-1H-indole as the dominant reaction product. The 3-bromo-5-methyl tautomer could not be isolated nor could its presence be identified in solution. However, traces of it were recognized in the crystal of 5-bromo-3-methyl tautomer as a binary solid solution. In silico studies provided the physicochemical parameters of all compounds, enabling the estimation of some derivatives affinity to certain enzymes. In vitro evaluation of the hemolytic and cytoprotective properties of all derivatives showed that most of the compounds exhibited no hemolytic activity, while all demonstrated significant cytoprotective effects on human erythrocytes under oxidative stress.
近年来，我们注意到对分子杂交的兴趣日益浓厚，分子杂交涉及将化学和药理学上不同的片段组合成单个分子。在本研究中，我们设计并合成了一系列在吡唑环上有不同取代基的吲哚 - 吡唑杂化物。通过光谱方法对这些化合物进行了表征，并且大多数化合物的结构通过X射线分析得到了证实。3 - （二甲基氨基甲基）吲哚与溴甲基吡唑衍生物的反应以互变异构体选择性模式进行：从4 - 溴 - 3 - 甲基 - 1 - 吡唑得到的4 - 溴 - 3（5） - 甲基 - （（1 - 吡唑 - 1 - 基）甲基） - 1 - 吲哚互变异构体可以通过柱色谱法分离。相比之下，3 - 溴 - 5 - 甲基 - 1 - 吡唑产生（（5 - 溴 - 3 - 甲基 - 1H - 吡唑 - 1 - 基）甲基） - 1H - 吲哚作为主要反应产物。3 - 溴 - 5 - 甲基互变异构体无法分离，在溶液中也无法鉴定其存在。然而，在5 - 溴 - 3 - 甲基互变异构体的晶体中作为二元固溶体识别出了其痕量。计算机模拟研究提供了所有化合物的物理化学参数，从而能够估计某些衍生物对特定酶的亲和力。所有衍生物的溶血和细胞保护特性的体外评估表明，大多数化合物没有溶血活性，而所有化合物在氧化应激下对人红细胞均表现出显著的细胞保护作用。
