| 刘斌,徐小娜,仝红娟,朱周静,王艳娇,曹召勇.化学通报,2025,88(10):1109-1116,1097. |
| 新型氧杂环丁烷衍生物的合成及体外抗肿瘤活性研究 |
| Synthesis and in Vitro Antitumor Activity of Novel Oxocyclobutane Derivatives |
| 投稿时间：2025-03-11 修订日期：2025-08-14 |
| DOI： |
| 中文关键词: 氧杂环丁烷衍生物 抗肿瘤活性 条件优化 单晶结构 |
| 英文关键词:Oxocyclobutane derivatives Antitumor activity Condition optimization single crystal structure |
| 基金项目:咸阳市分子影像与药物合成重点实验室项目(2021QXNL-PT-0008)、陕西省自然科学基金项目(2025JC-YBMS-888) 和2024 年度陕 西省教育厅重点实验室项目(24JS004)资助 |
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| 中文摘要: |
| 报道一类结构新颖的氧杂环丁烷衍生物(5~8)的合成及体外抗肿瘤活性研究。首先,以4-(二氟甲氧基)苯磺酰氯(1)和3,4,5,6-四氢吡咯并[3,4-c]吡咯-2(1H)-甲酸叔丁酯(2)为原料,依次经历取代、脱Boc保护、Strecker等三步反应,得到氧杂环丁烷衍生物5。然后,化合物5与苯基溴化镁反应,得到氧杂环丁烷衍生物6和7,化合物5经双氧水氧化,得到氧杂环丁烷衍生物8。中间体及产物结构均经过1H NMR和ESI-MS表征,其中,化合物8的结构进一步通过XRD单晶衍射表征。然后分别考察关键步骤的主要影响因素,确定适宜的反应条件。最后选取HepG2肝癌细胞、结肠癌细胞LoVo细胞、人非小细胞肺癌A549细胞、人乳腺癌MCF-7细胞、人宫颈癌HeLa等5种肿瘤细胞及正常肝细胞LO2为测试细胞株,测试产物的体外抗肿瘤活性。结果表明,氧杂环丁烷衍生物(5~8)对5种肿瘤细胞均展现出了一定的抑制活性,尤其对HepG2肝癌细胞具有明显的抑制活性。其中,化合物8对HepG2细胞的抑制活性最强(IC50= 0.9 ± 0.2 μM)。此外,化合物5~8对正常的肝细胞LO2没有显示出明显的毒性。 |
| 英文摘要: |
| The synthesis and in vitro antitumor activity of a class of novel oxocyclobutane derivatives (5 ~ 8) were reported. Firstly, 4-(difluoromethoxy)benzenesulfonyl chloride (1) and tert-butyl 3,4,5,6-tetrahydro-2-pyrrolylacetate (2) were used as raw materials, and three steps of reactions including substitution, de-Boc protection and Strecker reaction were undergone successively to obtain the oxocyclobutane derivative 5. Then, oxocyclobutane derivatives 6 and 7 were obtained by the reaction of compound 5 with phenylmagnesium bromide. Also, compound 5 was oxidized with hydrogen peroxide to give oxocyclobutane derivative 8. The structures of intermediates and products were characterized by 1H NMR and ESI-MS and the structure of compound 8 was further characterized by XRD single crystal diffraction. Then, the main influencing factors of the key steps were investigated respectively, and appropriate reaction conditions were determined. Finally, five tumor cell lines including HepG2 hepatocellular carcinoma cells, LoVo colorectal cancer cells, A549 small cell lung cancer cells, MCF-7 breast cancer cells, HeLa cervical cancer cells, and normal liver cells LO2 were selected as test cell lines to the in vitro antitumor activity of the products. The results showed that the oxocyclobutane derivatives (5 ~ 8) exhibited certain inhibitory activities against the five types of tumor cells, especially significant inhibitory activity against HepG2 liver cancer cells. Among them, compound 8 showed the strongest inhibitory activity against HepG2 cells (IC?? = 0.9 ± 0.2 μM). In addition, compounds 5 ~ 8 did not show obvious toxicity to normal liver cells LO2. |
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