Department of Chemistry, Faculty of Science & Arts, Ordu University, 52200 Ordu, Turkey.
Molecules. 2020 Feb 18;25(4):900. doi: 10.3390/molecules25040900.
In this paper, a series of new substituted-5-pyrazolones were first synthesized, then formulated by the Vilsmeier-Haack reaction to obtain substituted-4-carbaldehyde-5-pyrazolones. In the final step, when urea was reacted with formulated pyrazolones, we found that, instead of the C=N bond in azomethine form, the compounds tautomerized to form a series of novel pyrazole-4-ylidenemethylurea structures. The structures of these compounds were elucidated by FTIR, H, C NMR, LC-MS/MS, and elemental analysis methods. The cytotoxic and antioxidant effects of substituted 5-pyrazolones and their pyrazolone-urea derivatives were investigated in metastatic A431 and noncancerous HaCaT human keratinocytes by a mitochondrial activity test. The effects of the compounds on the migration of cancerous and noncancerous cell lines were investigated by using a cell scratch assay. The General Linear Model, Statistical Package for Social Sciences (SPSS v26) was used to determine if there was a statistically significant difference between the control and the treatment groups. Four of the nine compounds showed an antioxidant effect. All 5-pyrazolone-urea compounds showed higher toxicity ( < 0.05) in cancerous A431 cells compared to noncancerous cells at all time points. All compounds also showed a biphasic hormetic effect. Four of the nine compounds inhibited cell migration.
本文首次合成了一系列新的取代-5-吡唑酮，然后通过 Vilsmeier-Haack 反应将其配方制成取代-4-醛基-5-吡唑酮。在最后一步，当脲与配方中的吡唑酮反应时，我们发现，化合物不是互变异构为亚甲胺形式的 C=N 键，而是发生互变异构形成一系列新型的吡唑-4-亚甲基脲结构。这些化合物的结构通过 FTIR、H、C NMR、LC-MS/MS 和元素分析方法进行了阐明。通过线粒体活性测试，在转移性 A431 和非癌细胞 HaCaT 人角质细胞中研究了取代 5-吡唑酮及其吡唑酮脲衍生物的细胞毒性和抗氧化作用。通过细胞划痕试验研究了化合物对癌细胞和非癌细胞系迁移的影响。使用一般线性模型、社会科学统计软件包（SPSS v26）来确定对照组和治疗组之间是否存在统计学上的显著差异。在九种化合物中有四种具有抗氧化作用。所有 5-吡唑酮脲化合物在所有时间点在癌细胞 A431 中的毒性均高于非癌细胞（<0.05）。所有化合物还表现出双相 hormetic 效应。在九种化合物中有四种抑制细胞迁移。
