Synthesis, characterization and biological activity of 5-fluorouracil derivatives of rare earth (Gd, Dy, Er) substituted phosphotungstate

• We synthesized three new POMs derivatives containing 5-fluorouracil and rare earth.
• In vitro antitumor activity toward HeLa and HepG-2 was examined by MTT method.
• Compounds are superior to corresponding rare earth derivatives and 5-fluorouracil.
• TI values shows compounds are more safety and potentially to be antitumor drugs.

Three new rare earth (Gd, Dy, Er) substituted phosphotungstates containing 5-fluorouracil, K10C4H4FN2O2Gd(PW11O39)2·8H2O, K10C4H4FN2O2Dy(PW11O39)2·9H2O and K9(C4H4FN2O2)2Er(PW11O39)2·10H2O, were synthesized by degradation method and self-assembly method. Analytical results demonstrated that the Keggin polyanion and the pyrimidine ring of 5-FU were maintained in its structures, and TG test shown compounds have good thermostability. MTT assay was used to measure its antitumor activity against HeLa and HepG-2 cells, and their cytotoxicity toward HEK293 cell. Results show that the IC50 of title compounds against HeLa and HepG-2 tumor cells are 7.14, 6.16, 5.95 μmol L−1 and 5.62, 5.96, 6.88 μmol L−1, respectively. And their antitumor activity are superior to rare earth substituted phosphotungstates K11Gd(PW11O39)2·15H2O, K11Dy(PW11O39)2·10H2O, K11Er(PW11O39)2·10H2O and 5-fluorouracil. Which suggests title compounds have excellent antitumor activity due to the synergistic effect between 5-fluorouracil group, rare earth ions and Keggin polyanions.

The synthesized POMs derivatives containing rare earth and 5-fluorouracil 1–3 show higher in vitro antitumor activity than rare earth derivatives 4–6, and low cytotoxicity against HEK293 were also maintained.Figure optionsDownload as PowerPoint slide