| 宋云飞,万 方,程 辟,高 童,戚媛媛,张婉秋,谢伟东.新化合物大麻二酚衍生物CBD-S的合成及体外活性研究[J].,2023,(8):1410-1415 |
| 新化合物大麻二酚衍生物CBD-S的合成及体外活性研究 |
| Synthesis and Investigation Into in Vitro Activities of a New Cannabidiol Derivative CBD-S |
| 投稿时间：2022-09-27 修订日期：2022-10-23 |
| DOI：10.13241/j.cnki.pmb.2023.08.003 |
| 中文关键词: 大麻二酚 大麻二酚2,6-苯氧乙酸二钠盐 炎症 肿瘤 环氧合酶-2 |
| 英文关键词: CBD CBD-S Inflammation Tumor COX-2 |
| 基金项目:国家自然科学基金项目（81373460）；深圳市高校稳定支持项目（WDZC20200820150804001） |
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| 中文摘要: |
| 摘要 目的：大麻二酚（CBD）具有抗肿瘤和抗炎活性，是一种非成瘾性的活性成分，近年来受到医药界的广泛关注，但其水溶性较差，限制了其临床应用。本文拟合成一种新型的水溶性化合物，并测试其抗肿瘤与抗炎活性。方法：本文主要基于CBD进行结构改造，化学合成了新化合物大麻二酚2,6-苯氧乙酸二钠盐（CBD-S），通过核磁共振氢谱、碳谱和高分辨质谱对其化学结构进行了表征，通过高效液相色谱（HPLC）方法测试了其溶解性。同时在HepG2(人肝癌细胞)和J774A.1(小鼠单核巨噬肿瘤细胞系)细胞上分别通过噻唑蓝（MTT）和Western blotting的方法测试了其体外抗细胞增殖及抗炎活性。结果：我们成功获得了CBD-S新化合物，氢谱、碳谱和高分辨质谱鉴定结果证实新合成的CBD-S结构正确，HPLC方法测试结果显示该化合物具有较好的水溶性。在细胞增殖实验中，我们发现该化合物在细胞培养液中终浓度为5-10 μg/mL时，以剂量依赖性方式显著抑制人肝癌HepG2细胞的增殖。在细胞抗炎活性研究中，为了获得在J774A.1细胞上的安全无毒浓度来开展后续的活性测试，我们首先检测了该化合物在J774A.1细胞上的毒性，发现在该细胞系温孵CBD-S在细胞培养液中终浓度为10 μg/mL以下时，是没有细胞毒的。接下来，在J77A.1细胞，我们发现CBD-S在细胞培养液中终浓度为0.01-1.00 μg/mL时，显著抑制了脂多糖（LPS）诱导的环氧合酶-2（COX-2）蛋白的生成。结论：新合成的化合物CBD-S具有较好的水溶性，在体外具有一定的抗肿瘤与抗炎活性，提示其具有较好的应用前景，值得进一步的深入或体内验证研究。 |
| 英文摘要: |
| ABSTRACT Objective: Cannabidiol (CBD) is a non-addictive active ingredient with anti-tumor and anti-inflammatory activities. Therefore, it has attracted more attention in the pharmaceutical industry in recent years, but its poor water solubility limits its further clinical application. This article aimed to synthesize a new water-soluble compound and test its anti-tumor and anti-inflammatory activities. Methods: The new compound cannabinol 2,6-phenoxyacetic acid disodium salt (CBD-S) was chemically synthesized based on CBD. Chemical structure of CBD-S was characterized by nuclear magnetic resonance hydrogen spectroscopy, carbon spectroscopy and high-resolution mass spectrometry, and its solubility was tested by high performance liquid chromatography (HPLC). Simultaneously, cell proliferation and anti-inflammatory activities of CBD-S in vitro were studied by MTT and Western blotting methods respectively on HepG2 (human liver cancer cell line) and J774A.1 (mouse monocyte-macrophage tumor cell line) cells. Results: We successfully obtained a new CBD-S compound. The results of hydrogen spectrum, carbon spectrum and high-resolution mass spectrometry confirmed that the structure of the newly synthesized CBD-S was correct. The results of HPLC method showed that the compound had good water solubility. In the cell proliferation experiment, we found that when the final concentration of this compound in the cell culture medium was 5-10 μg/mL, it significantly inhibited the proliferation of human hepatoma HepG2 cells in a dose-dependent manner. In the study of cellular anti-inflammatory activity, in order to obtain non-toxic concentrations to carry out subsequent pharmacological experiments, we first detected the toxicity of the compound in J774A 1 Cells. It was found that when the final concentration of CBD-S incubated in this cell line was below 10 μg/mL in cell culture medium, there was no cytotoxicity. Next, in J77A. 1 cells, we found that when the final concentration of CBD-S in cell culture medium was 0.01-1.00 μg/mL, it significantly inhibited the production of cyclooxygenase-2 (COX-2) protein induced by lipopolysaccharide(LPS). Conclusion: The newly synthesized compound CBD-S has good water solubility and certain anti-tumor and anti-inflammatory activities in vitro, suggesting that it will has a good application prospect, and worth for further studies in-depth or in vivo validation. |
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