Syntheses, antitumor activities, and antiangiogenesis of exo-3,6-epoxy-1,2,3,6-tetrahydrophthalimidoethanoyl-5-fluorouracil and its polymers

A new monomer, exo-3,6-epoxy-1,2,3,6-tetrahydrophthalimidoethanoyl-5-fluoro uracil (ETFU), was synthesized by the reaction of exo-3,6-epoxy-1,2,3,6-tet rahydrophthalimidoethanoyl chloride (ETPC) and 5-fluorouracil (5-FU). The h omopolymer of ETFU and its copolymers with acrylic acid (AA) and vinyl acet ate (VAc) were prepared vi a photopolymerizations with 2,2-dimethoxy-2-phen ylacetophenone at 25 degreesC for 48 h. The structures of the synthesized m onomer and polymers were identified by Fourier transform infrared, H-1 NMR, and C-13 NMR spectroscopy and elemental analysis. The ETFU contents in pol y(ETFU-co-AA) and poly(ETFU-co-VAc) were 26 mol % and 26 mol %, respectivel y. The number-average molecular weights of the polymers, as determined by g el permeation chromatography, ranged from 5600 to 17,000. The in vitro cyto toxicities of 5-FU and the synthesized samples against mouse mammary carcin oma and human histiocytic lymphoma cancer cell lines increased in the follo wing order: ETFU > 5-FU > poly(ETFU-co-AA) > poly(ETFU) > poly(ETFU-co-VAc) . The in vivo antitumor activities of the polymers against Balb/C mice bear ing the sarcoma 180 tumor cells were greater than those of 5-FU at all dose s tested. The inhibitions of the samples for SV40 DNA replication and antia ngiogenesis were much greater than the inhibition of the control. (C) 2000 John Wiley & Sons, Inc.