Abstract
OBJECTIVES: To reduce the toxicity of 5-fluorouracil (5-FU), design and synthesize 5-FU-lactoside derivatives, and preliminarily study their antitumor activities. METHODS: Target compounds were prepared with Vorbrüggenglycation procedures, the structures were characterized through high resolution mass spectrometry (HRMS), (1)H nuclear magnetic resonance ((1)HNMR), carbon-13 nuclear magnetic resonance ((13)CNMR), heteronuclear multiple quantum correlation (HMQC), and heteronuclear multiple bond correlation (HMBC). A cell counting kit (CCK)-8 test was performed to examine their in vitro toxicity and antitumor activity. Experimental data were tested by χ(2), and statistically significant differences were denoted by P<0.05. RESULTS: The target compounds were synthesized through a simple and efficient method. (1)HNMR, (13)CNMR, HMQC, HMBC, and HRMS confirmed that Ⅰa and Ⅰb 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(-1)) of Ⅰa and Ⅰb 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%; P<0.05). Ⅰb 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(-1) for 24 h were 81.20% and 80.19%, respectively. CONCLUSIONS: Ⅰa and Ⅰb are less toxic than 5-FU. The antitumor activity of Ⅰb against oral squamous cell carcinoma cells is more obvious than that of Ⅰa.