Syntheses and antitumor activities of polymers containing amino acid and 5-fluorouracil moieties

The new monomer, 3,6-endo-methylene-1,2,3,6-tetrahydrophthalimidoethanoyl-5-fluorouracil (ETEFU), was synthesized from 5-fluorouracil (5-FU) and 3,6-endo-methylene-1,2,3,6-tetrahydophthalimidoethanoyl chloride (ETEC). Its homopolymer and copolymers with acrylic acid (AA) and vinyl acetate (VAc) were prepared by photopolymerization reactions using 2,2-dimethoxy-2-phenylacetophenone (DMP) as the photoinitiator. The synthesized ETEFU and polymers were identified by FT-IR, 1H-NMR, and 13C-NMR spectra. The contents of ETEFU units in poly(ETEFU-co-AA) and poly(ETEFU-co-VAc) were 20 and 17 mol%, respectively. The number-average molecular weights of the synthesized polymers determined by gel permeation chromatography (GPC) were 4,600 to 10,700 g mol−1. In vitro cytotoxicities of samples were evaluated with cancer cell lines [mouse mammary carcinoma (FM3A), mouse leukemia (P388), and human histiocytic lymphoma (U937)] and a normal cell line [mouse liver cells (AC2F)]. Cytotoxicities of 5-FU and synthesized samples against the cancer cell lines were ranked as follows: ETEFU > poly(ETEFU) > 5-FU > poly(ETEFU-co-AA) > poly(ETEFU-co-VAc). The in vivo antitumor activities of poly(ETEFU) and poly(ETEFU-co-AA) against Balb/C mice bearing the sarcoma 180 tumor cells were greater than those of 5-FU at all doses except for the activity of poly(ETEFU) at 0.8 mg/kg.