Synthesis And Anti-tumor Effect Of (5-Fluorouracil-1-Acetic Acid)-4'-Curcuminate

Introduction:Curcumin is a phenolic compound isolated from turmeric(Curcuma longa L.),it is the most important Pharmacological ingredient of turmeric. Curcumin has lots of pharmacological effects such as anti-tumor, anti gallstones, inflammation, free radicals, improving immunity and so on while it is chemically unstable like easily oxidized in air and degraded in alkaline environment. Its bioavailability is low since there is no better formulation for clinical and transformation of its structure will improve its stability and bioavailability.5-fluorouracil is pyrimidine antimetabolites,it has served as the preferred treatment of gastric cancer, colorectal cancer, breast cancer since it been invented, however, 5 - fluorouracil has low fat-solubility and significant first-pass elimination and many clinical adverse reactions which limited its further application. Compared with the 5-fluorouracil ,many 5-fluorouracil derivatives have stronger effect and lower toxicity and more convenient route of administration ,while those results proved reformation of 5-fluorouracil structure will creat more effective drug.Therefore,we synthesised a new compound which prepared from esterification response of curcumin and 5-fluorouracil and expect to achieve the purpose of synergies, reduced side effects and extending the role of time.OBJECTIVE: To synthesis the (5-fluorouracil-1-acetic acid)-4′-curcuminate and investigate the anti-tumor effect of it.METHODS:(1) The 5-fluorouracil (5-FU) and chloroacetic acid react in the alkaline environment to prepare 5-fluorouracil-1-acetic acid,then react with curcumin by the esterification response to prepare (5-fluorouracil-1-acetic acid)-4′-curcuminate;(2) Cell proliferation was assayed by MTT method to explore the cytotoxicity on HL60, K562,SGC7901,SW480 cells of (5-fluorouracil-1-acetic acid)-4′-curcuminate in vitro;(3) The tumor model in mice was established by H22 and S180,then the antitumor effect of (5-fluorouracil-1-acetic acid)-4′-curcuminate in vivo was analyzed.RESULTS:(1)The (5-fluorouracil-1-acetic acid)-4′-curcuminate has not been reported and its structure identificated by mass spectrometry and nuclear magnetic;(2) (5-fluorouracil-1-acetic acid)-4′-curcuminate has cytotoxicity on HL60,K562,SGC7901,SW480 cells and its IC50 close to curcumin;(3)The antitumor effect of (5-fluorouracil-1-acetic acid)-4′-curcuminate to H22 was clear by abdominal cavity injection administration then to S180 was ineffective.CONCLUSION: (5-fluorouracil-1-acetic acid)-4′-curcuminate showed anti-tumor effect in vivo and in vitro then its effects and mechanism study will be more thorough.