SYNTHESES AND BIOLOGICAL-ACTIVITIES OF 6-EPOXY-1,2,3,6-TETRAHYDROPHTHALAYL-5-FLUOROURACIL AND ITS POLYMERS

The new monomer, 6-epoxy-1,2,3,6-tetrahydrophthaloyl-5-fluorouracil (M ETFU), was synthesized by the reaction of 5-fluorouracil (5-FU) and ex o-3,6-epoxy-1,2,3,6-tetrahydrophthalic anhydride (ETA) in order to pre pare polymers containing 5-FU moiety. -epoxy-1,2,3,6-tetrahydrophthalo yl-5-fluorouracil) [poly(METFU)], yl-5-fluorouracilthaloyl-5-fluoroura cil-co-acrylic acid) [poly(METFU-co-AA)], and xo3,6-epoxy-1,2,3,6-tetr ahydrophthaloyl-5-acetate) [[poly(METFU-co-VAc)] were synthesized by p hotopolymerizations using 2, 2-dimethoxy-2-phenylacetophenone (DMP) as an initiator. The synthesized METFU and the polymers were identified by FTIR and H-1-NMR spectroscopies. The contents of METFU in poly(METF U-co-AA) and poly(METFU-co-VAc) determined by elemental analysis were 52 and 60 mol %, respectively. The average molecular weights and polyd ispersity indices determined with GPC were as follows: (M) over bar n = 9,400, (M) over bar w, = 11,400 (M) over bar w/(M) over bar n = 1.21 for poly(METFU), (M) over bar n = 14,400, (M) over bar w = 26,800, (M ) over bar w/(M) over bar n = 1.86 for poly(METFU-co-AA), and (M) over bar n = 23,100, (M) over bar w = 33,000, (M) over bar w/(M) over bar n = 1.43 for poly(METFU-co-VAc). The in vitro cytotoxicities of sample s were evaluated with mouse mammary carcinoma (FM3A), mouse leukemia ( P388), and human histiocytic lymphoma (U937) as cancer cell lines, and mouse liver cells (AC2F) as a normal cell line. The in vivo antitumor activities of synthesized polymers against mice bearing the sarcoma 1 80 tumor cell Line were greater than those of 5-FU at concentrations o f 0.8 and 80 mg/kg. (C) 1998 John Wiley & Sons, Inc.