| 引用本文： |
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钟智薇,祝志凌,展军颜,吴玉兰,刘志平,苏毅,甘春芳.3-生物素-B-降胆甾苯并咪唑化合物的非靶标代谢组学[J].广西科学院学报,2024,40(4):459-468. [点击复制]
- ZHONG Zhiwei,ZHU Zhiling,ZHAN Junyan,WU Yulan,LIU Zhiping,SU Yi,GAN Chunfang.Untargeted Metabolomics Focused on 3-biotin-B-nor-cholesterol Benzimidazole Analogues[J].Journal of Guangxi Academy of Sciences,2024,40(4):459-468. [点击复制]
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| 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，以及化合物结构中取代基不同对人卵巢癌细胞(SKOV3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能抑制氨基酰基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(DNA合成期)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：10.13657/j.cnki.gxkxyxb.20241226.010 |
| 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(2023GXNSFAA026399，2021GXNSFAA220104，2023GXNSFDA026063)和大学生创新训练项目(202310603066)资助。 |
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| Untargeted Metabolomics Focused on 3-biotin-B-nor-cholesterol Benzimidazole Analogues |
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ZHONG Zhiwei, ZHU Zhiling, ZHAN Junyan, WU Yulan, LIU Zhiping, SU Yi, GAN Chunfang
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| (Guangxi Key Laboratory of Natural Polymer Chemistry and Physics, School of Chemistry and Material, Nanning Normal University, Nanning, Guangxi, 530001, China) |
| Abstract: |
| In order to study the target of 3-biotin-B-nor-cholesterol benzimidazole compounds 1 and 2 on tumor cells,and the differences in the effects of different substituents in the structure of compounds on human ovarian cancer cells (SKOV3 cells),the mechanism of action of compounds was analyzed.The non-targeted metabolomics method was used to analyze the metabolites of treated SKOV3 cells by ultra-high performance liquid chromatography (UPLC) and high-performance resolution mass spectrometry (QE) tandem mass spectrometry (UHPLC-QE-MS),and the metabolites of the control group were compared.The results showed that compound 1 inhibited the biosynthesis of aminoacyl tRNA and decreased the expression of Bcl-2,thereby apoptosis and S phase (DNA synthesis phase) arrest of the cell cycle.Compound 2 inhibited the synthesis of cellular proteins, blocked the synthesis and mutual transformation of amino acids,affected the regulation of endogenous metabolism,and inhibited the expression of related genes and RNA synthesis.In summary,compounds 1 and 2 exert antitumor effects by interfering with amino acid metabolism and protein synthesis of SKOV3 cells and slowing down energy metabolism. |
| Key words: B-nor-cholesterol compounds benzimidazole non-targeted metabolomics cell cycle cell apoptosis |
