| 李亚梅,刘传峰,孙驰宇,张大军,栾天.化学通报,2022,85(7):833-838. |
| 含硫醚、硒醚及二硫键链接侧链的小檗碱衍生物的合成及体外抗肿瘤活性 |
| Synthesis of Novel Berberine-linked Disulfide, Thioether or Selenium Ether Moieties as Potent Cytotoxic Agents |
| 投稿时间：2021-11-22 修订日期：2021-12-28 |
| DOI： |
| 中文关键词: 小檗碱 硫醚 硒醚 二硫键 |
| 英文关键词:Berberine, Thioether, Selenide, Disulfide |
| 基金项目:辽宁省科学技术计划项目 |
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| 中文摘要: |
| 为开发高效低毒的抗肿瘤天然产物衍生物，依据药物拼合原理设计并合成了10个新型小檗碱衍生物。将盐酸小檗碱与含单硫醚、单硒醚和二硫键脂肪链片段通过缩合反应得到目标化合物，其化学结构均经过核磁共振氢谱﹑碳谱以及高分辨质谱的联合确证；采用噻唑蓝(MTT)法考察其体外抗肿瘤活性。结果表明，7个化合物针对不同的癌细胞株的抑制活性优于盐酸小檗碱，同时对人正常肝细胞L02的毒性较低。化合物3e的体外抗肿瘤活性最为理想(针对BEL-7402的IC50值为8.70 μmol/L，选择性指数为3.61)，可对其深入研究用以开发高效低毒的抗肿瘤药物。 |
| 英文摘要: |
| In order to develop efficient and low-toxic anti-tumor compounds, ten novel berberine derivatives were designed and synthesized based on the principle of pharmacochemical molecular combination. The target compounds were obtained by condensation reactions of berberine hydrochloride with different disulfide, thioether or selenium ether moieties, and their chemical structures were confirmed by 1H NMR, 13C NMR, and high-resolution mass spectrometry; Their in vitro antitumor activities were investigated by thiazole blue (MTT) method. The results showed that the inhibitory activity of the seven compounds against different cancer cell lines was better than that of berberine hydrochloride, while the toxicity to human normal hepatocytes L02 was lower. Compound 3e exhibited the best in vitro antitumor activity (IC50 value of 8.70 μmol/L and selectivity index of 3.61 against BEL-7402) and can be investigated in depth for the development of more efficient and less toxic antitumor drugs. |
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