Chobanov Nuri M, Dzhemileva Lilya U, Dzhemilev Usein M, D'yakonov Vladimir A
N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, Moscow 119991, Russia.
Antioxidants (Basel). 2024 Nov 25;13(12):1448. doi: 10.3390/antiox13121448.
The development of a methodology for the synthesis of new compounds with antitumor activity represents a significant and priority task within the field of medicinal chemistry. As a continuation of our research group's earlier studies on the antitumor activity of ionic derivatives of natural compounds, we have synthesized a series of previously undescribed pyrazole ionic compounds through a series of transformations of lithocholic acid methyl ester. To investigate the biological activity of the newly synthesized lithocholic acid derivatives, a series of modern flow cytometry techniques were employed to assess their cytotoxic activity, effects on the cell cycle, and induction of apoptosis. This included the analysis of alterations in the mitochondrial potential, accumulation of ROS ions in mitochondria, and loss of cytochrome c. These compounds demonstrate promising antitumor activity through their effects on mitochondrial oxidation and phosphorylation processes. These compounds, which we have designated as "soft dissociators", exhibit enhanced biopharmacological properties relative to the original lithocholic acid molecule.
开发具有抗肿瘤活性的新化合物的合成方法是药物化学领域的一项重要且优先的任务。作为我们研究小组早期关于天然化合物离子衍生物抗肿瘤活性研究的延续，我们通过一系列鹅去氧胆酸甲酯的转化反应，合成了一系列此前未描述过的吡唑离子化合物。为了研究新合成的鹅去氧胆酸衍生物的生物活性，我们采用了一系列现代流式细胞术技术来评估它们的细胞毒性活性、对细胞周期的影响以及凋亡诱导情况。这包括分析线粒体膜电位的变化、线粒体中活性氧离子的积累以及细胞色素c的丢失。这些化合物通过对线粒体氧化和磷酸化过程的影响展现出了有前景的抗肿瘤活性。我们将这些化合物命名为“软解离剂”，相对于原始的鹅去氧胆酸分子，它们具有增强的生物药理学特性。
