Mara Bogdan-Ionuț, Mioc Alexandra, Deveseleanu-Corici Livia-Nicoleta, Șoica Codruța, Cseh Liliana
Coriolan Dragulescu Institute of Chemistry, Romanian Academy, Bv. M. Viteazu, No. 24, 300223 Timișoara, Romania.
Faculty of Pharmacy, Victor Babes University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timișoara, Romania.
Int J Mol Sci. 2025 Jul 16;26(14):6823. doi: 10.3390/ijms26146823.
Thiophene derivatives are particularly attractive for application in drug development for their versatile pharmacological properties. We synthesized a series of four compounds with thiophene carboxamide as a scaffold. The structures were established based on HR-MS and 1D- and 2D-NMR. The purity of the compounds was established to be greater than 92% by thin-layer chromatography and NMR. The cytotoxic effects of the newly synthesized compounds were evaluated against the normal HaCaT cell line and A375, HT-29, and MCF-7 cancer cell lines. The cytotoxic assessment revealed that two compounds exhibit a significant cytotoxic effect on all cancer cell lines. To investigate their potential underlying mechanisms of action, several tests were performed: immunofluorescence imaging, caspase-3/7 assay, mitochondrial membrane potential (JC-1) assay, and 2',7'-dichlorofluorescein diacetate (DCFDA) assay. proved to be the most cytotoxic and effective in terms of caspase 3/7 activation, mitochondrial depolarization and decrease in ROS production; these effects did not occur in normal HaCaT cells, revealing that has a high selectivity against A375 cancer cells.
噻吩衍生物因其多样的药理特性在药物开发应用中特别具有吸引力。我们合成了一系列以噻吩甲酰胺为骨架的四种化合物。结构基于高分辨质谱（HR-MS）以及一维和二维核磁共振（1D-和2D-NMR）得以确定。通过薄层色谱法和核磁共振确定化合物纯度大于92%。评估了新合成化合物对正常HaCaT细胞系以及A375、HT-29和MCF-7癌细胞系的细胞毒性作用。细胞毒性评估显示，两种化合物对所有癌细胞系均表现出显著的细胞毒性作用。为研究其潜在的作用机制，进行了多项测试：免疫荧光成像、半胱天冬酶-3/7检测、线粒体膜电位（JC-1）检测以及二氯二氢荧光素二乙酸酯（DCFDA）检测。在半胱天冬酶3/7激活、线粒体去极化和活性氧生成减少方面被证明是细胞毒性最强且最有效的；这些效应在正常HaCaT细胞中未出现，表明其对A375癌细胞具有高选择性。
