Target compounds were prepared with Vorbrüggenglycation procedures, the structures were characterized through high resolution mass spectrometry (HRMS), ¹H nuclear magnetic resonance (¹HNMR), carbon-13 nuclear magnetic resonance (¹³CNMR), 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 χ², and statistically significant differences were denoted by P<0.05.

The target compounds were synthesized through a simple and efficient method. ¹HNMR, ¹³CNMR, 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.

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.