ObjectiveTo reduce the toxicity of 5-fluorouracil (5-FU), design and synthesize 5-FU-lactoside derivatives, and preliminarily study their antitumor activities.
MethodsTarget 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 theirin vitrotoxicity and antitumor activity. Experimental data were tested byχ2, and statistically significant differences were denoted byP<0 .05.
ResultsThe target compounds were synthesized through a simple and efficient method.1HNMR,13CNMR, HMQC, HMBC, and HRMS confirmed thatⅠaandⅠbwere 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) ofⅠaandⅠbinhibited 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).Ⅰbhad 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-1for 24 h were 81.20% and 80.19%, respectively.
ConclusionⅠaandⅠbare less toxic than 5-FU. The antitumor activity ofⅠbagainst oral squamous cell carcinoma cells is more obvious than that ofⅠa.
