Syntheses and biological activities of α-methoxy-exo-3,6-epoxy-1,2,3,6-tetrahydrophthaloyl-5-fluorouracil and its polymers

✍ Scribed by Won-Moon Choi; Il-Doo Chung; Neung-Ju Lee; Young-Woo Lee; Chang-Sik Ha; Won-Jei Cho

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 137 KB
• Volume: 36
• Category: Article
• ISSN: 0887-624X
• DOI: 10.1002/(sici)1099-0518(19980930)36:13<2177::aid-pola2>3.0.co;2-r

✦ Synopsis

The new monomer, ␣-methoxy-exo-3,6-epoxy-1,2,3,6-tetrahydrophthaloyl-5-fluorouracil (METFU), was synthesized by the reaction of 5-fluorouracil (5-FU) and exo-3,6-epoxy-1,2,3,6-tetrahydrophthalic anhydride (ETA) in order to prepare polymers containing 5-FU moiety. Poly(␣-methoxy-exo-3,6-epoxy-1,2,3,6-tetrahydrophthaloyl-5-fluorouracil) [poly(METFU)], poly(␣-methoxy-exo-3,6-epoxy-1,2,3,6-tetrahydrophthaloyl-5-fluorouraci-co-acrylic acid) [poly(METFU-co-AA)], and poly(␣-methoxy-exo-3,6-epoxy-1,2,3,6-tetrahydrophthaloyl-5-fluorouracil-co-vinyl acetate) [poly(METFU-co-VAc)] were synthesized by photopolymerizations using 2,2-dimethoxy-2-phenylacetophenone (DMP) as an initiator. The synthesized METFU and the polymers were identified by FTIR and 1 H-NMR spectroscopies. The contents of METFU in poly-(METFU-co-AA) and poly(METFU-co-VAc) determined by elemental analysis were 52 and 60 mol %, respectively. The average molecular weights and polydispersity indices determined with GPC were as follows: M n ϭ 9,400, M w ϭ 11,400 M w/M n ϭ 1.21 for poly(METFU), M n ϭ 14,400, M w ϭ 26,800, M w/M n ϭ 1.86 for poly(METFU-co-AA), and M n ϭ 23,100, M w ϭ 33,000, M w/M n ϭ 1.43 for poly(METFU-co-VAc). The in vitro cytotoxicities of samples 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 180 tumor cell line were greater than those of 5-FU at concentrations of 0.8 and 80 mg/kg.