| 摘要: |
| 为探讨3-生物素-B-降胆甾苯并咪唑化合物1和2对肿瘤细胞的作用靶点，探讨化合物结构中取代基不同对SKOV3细胞（人卵巢癌细胞）的作用差异，分析化合物的作用机制。采用非靶向代谢组学方法，通过超高效液相色谱(UPLC)与高效分辨质谱(QE)的串联质谱技术(UHPLC-QE-MS)，对处理后的SKOV3细胞代谢产物进行分析，与对照组的代谢产物进行差异比较。结果表明，化合物1抑制氨基酰基tRNA的生物合成，降低Bcl-2的表达，从而诱导细胞周期的凋亡和s期阻滞。化合物2能抑制细胞蛋白的合成，阻断氨基酸的合成和相互转化，影响内源性代谢调节，抑制相关基因表达及RNA合成。综上所述，化合物1和2通过干扰SKOV3细胞的氨基酸代谢和蛋白质合成，减缓能量代谢，发挥了抗肿瘤作用。 |
| 关键词: B-降胆甾化合物,苯并咪唑,非靶向细胞代谢组学,细胞周期,细胞凋亡 |
| DOI： |
| 投稿时间：2024-09-23修订日期：2024-10-23 |
| 基金项目:广西自然科学基金项目 |
|
| Off-target metabolomics of 3-biotin-B-norcholesterol benzimidazole compounds |
|
zhongzhiwei
|
| (Nanning Normal University) |
| Abstract: |
| In order to study the target of 3-biotin-B-norcholesterol benzimidazole compounds 1 and 2 on tumor cells, we discussed the different substituent groups in the structures of the compounds on SKOV3 cells and analyzed the mechanism.The metabolites of treated SKOV3 cells were analyzed using an untargeted metabolomics approach by ultra-high-performance liquid chromatography (UPLC) coupled with high-performance resolution mass spectrometry (QE) in tandem with mass spectrometry (UHPLC-QE-MS) to differentially compare the metabolites of the treated SKOV3 cells with those of the control group. The results showed that compound 1 inhibited aminoacyl tRNA biosynthesis and decreased Bcl-2 expression, thereby inducing apoptosis and s-phase blockade of the cell cycle. Compound 2 inhibited cellular protein synthesis, blocked amino acid synthesis and interconversion, affected endogenous metabolic regulation, and inhibited related gene expression and RNA synthesis. In summary, compounds 1 and 2 exerted antitumor effects by interfering with amino acid metabolism and protein synthesis and slowing down energy metabolism in SKOV3 cells. |
| Key words: B-nor-cholesterol benzimidazole untargeted cell metabolomics cell-cycle apoptosis |
