Zhang Yuting, Liu Jiang, Zhao Hang, He Yang, Chen Qianming
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management & Dept. of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
Targeted Tracer Research and Development Laboratory, Frontiers Science Center for Disease-related Molecular Network, Dept. of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
Hua Xi Kou Qiang Yi Xue Za Zhi. 2022 Jan 25;40(1):32-38. doi: 10.7518/hxkq.2022.01.005.
To reduce the toxicity of 5-fluorouracil (5-FU), design and synthesize 5-FU-lactoside derivatives, and preliminarily study their antitumor activities.
Target compounds were prepared with Vorbrüggenglycation procedures, the structures were characterized through high resolution mass spectrometry (HRMS), H nuclear magnetic resonance (HNMR), carbon-13 nuclear magnetic resonance (CNMR), heteronuclear multiple quantum correlation (HMQC), and heteronuclear multiple bond correlation (HMBC). A cell counting kit (CCK)-8 test was performed to examine their toxicity and antitumor activity. Experimental data were tested by , and statistically significant differences were denoted by <0.05.
The target compounds were synthesized through a simple and efficient method. HNMR, CNMR, HMQC, HMBC, and HRMS confirmed that and were 5-FU nucleoside derivatives substituted with lactoside groups at N-1 and N-3, respectively. The CCK-8 test verified that high concentrations (0.7 μmol·mL) of and inhibited the growth of normal oral keratinocytes (NOK) by 30.28% and 50.68% after 24 h of treatment. Both values were lower than the inhibitory effect of 5-FU (68.22%; <0.05). had a significant inhibitory effect on the growth of two oral squamous cell carcinoma cell lines. The inhibition rates of Cal-27 cells and UM SCC-47 cells treated with 0.7 μmol·mL for 24 h were 81.20% and 80.19%, respectively.
and are less toxic than 5-FU. The antitumor activity of against oral squamous cell carcinoma cells is more obvious than that of .
为降低5-氟尿嘧啶（5-FU）的毒性，设计并合成5-FU-乳糖苷衍生物，并初步研究其抗肿瘤活性。
采用 Vorbruggen 糖基化方法制备目标化合物，通过高分辨质谱（HRMS）、氢核磁共振（HNMR）、碳-13 核磁共振（CNMR）、异核多量子相关（HMQC）和异核多键相关（HMBC）对结构进行表征。采用细胞计数试剂盒（CCK）-8 试验检测其毒性和抗肿瘤活性。实验数据经 检验，差异有统计学意义以<0.05表示。
通过简单高效的方法合成了目标化合物。HNMR、CNMR、HMQC、HMBC 和 HRMS 证实 和 分别为在 N-1 和 N-3 位被乳糖苷基团取代的 5-FU 核苷衍生物。CCK-8 试验证实，高浓度（0.7 μmol·mL）的 和 在处理 24 h 后对正常口腔角质形成细胞（NOK）生长的抑制率分别为 30.28%和 50.68%。这两个值均低于 5-FU 的抑制作用（68.22%；<0.05）。 对两种口腔鳞状细胞癌细胞系的生长具有显著抑制作用。用 0.7 μmol·mL 的 处理 Cal-27 细胞和 UM SCC-47 细胞 24 h 的抑制率分别为 81.20%和 80.19%。
和 的毒性低于 5-FU。 对口腔鳞状细胞癌细胞的抗肿瘤活性比 更明显。
