Synthesis of 5-fluorouracil-lactoside derivatives and experimental study on their anti-oral squamous cell carcinoma activity.

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), 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.

RESULTS

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.

CONCLUSIONS

and are less toxic than 5-FU. The antitumor activity of against oral squamous cell carcinoma cells is more obvious than that of .