Syntheses of polyrotaxane conjugated with 5-fluorouracil and vitamins with improved antitumor activities

New antitumor active polyrotaxanes, presynthesized from ??-cyclodextrin and polypropylene glycol, were first end capped with antitumor active drug, 5-fluorouracil, and further conjugated with 5-fluorouracil and various bioactive vitamin derivatives such as succinyl vitamin B2 (PRTVB2) and ascorbic acid 6-palmitate (PRTASP). FT-IR, 1H, and 13C-NMR spectroscopies and elemental analysis were used to characterize the synthesized polyrotaxane and degree of 5-fluorouracil/vitamins substitution to ??-cyclodextrin. The in vitro cytotoxicities of polyrotaxane conjugates were evaluated with mouse mammary carcinoma (FM3A), mouse leukemia (P388), human histiocytic lymphoma (U937) as cancer cell lines, and mouse liver cells (AC2F) as a normal cell line. The cytotoxicities of the polyrotaxane-ascorbic acid conjugates against AC2F normal cell line decreased more than 18,000% as compared with those of 5-fluorouracil. The in vivo antitumor activities of synthesized 5-fluorouracil-1-acetic acid-polyrotaxane (5-FUA-PRT) against mice bearing sarcoma 180 tumor cell line were greater than of 5-fluorouracil at concentration of 800 mg/kg