Syntheses, antitumor activities, and antiangiogenesis of a monomer and itsmedium molecular weight polymers: Maleimidoethanoyl-5-fluorouracil and itspolymers

A new monomer, maleimidoethanoyl-5-fluorouracil (MIEFU), was synthesized by the reaction of maleimidoethanoyl chloride and 5-fluorouracil (5-FU). The homopolymer of MIEFU and its copolymers with acrylic acid (AA) or vinyl ace tate (VAc) were prepared by photopolymerizations with 2,2-dimethoxy-2-pheny lacetophenone as an initiator at 25 degrees C for 48 h. The structures of t he synthesized monomer and polymers were identified by Fourier transform in frared,H-1 NMR, and C-13 NMR spectroscopies and elemental analysis. The con tents of the MIEFU units in poly(MIEFU-co-AA) and poly(MIEFU-co-VAc) were 1 8 and 30 mol %, respectively. The number-average molecular weights of the s ynthesized polymers, as determined by gel permeation chromatography, ranged from 4900 to 9800. The in vitro cytotoxicities of the samples against mous e mammary carcinoma (FM3A), mouse leukemia (P388), and human histiocytic ly mphoma (U937) cancer cell lines decreased in the following order: 5-FU grea ter than or equal to MIEFU > poly(MIEFU) > poly(MIEFU-co-AA) > poly(MIEFU-c o-VAc). The in vivo antitumor activities of the polymers against Balb/C mic e bearing the sarcoma 180 tumor cells were greater than those of 5-FU at al l the doses tested. The inhibitions of the SV40 DNA replication of the samp les were much greater than that of the control. The synthesized monomer and polymers showed more antiangiogenesis activity than the control. (C) 2000 John Wiley & Sons, Inc.