Synthesis and biological activity of medium range molecular weight polymers containing exo-3,6-epoxy-1 2,3,6-tetrahydrophthalimidocaproic acid

A new monomer, exo-3,6-epoxy-1,2,3,6-tetrahydrophthalimidocaproic acid (ETCA), was prepared by reaction of maleimidocaproic acid and furan. The homopolymer of ETCA and its copolymers with acrylic acid (AA) or with vinyl acetate (VAc) were obtained by photopolymerizations using 2,2-dimethoxy-2-phenylacetophenone as an initiator at 25 degreesC. The synthesized ETCA and its polymers were identified by FTIR, H-1 NMR and C-13 NMR spectroscopies. The apparent average molecular weights and polydispersity indices determined by gel permeation chromatography (GPC) were as follows: M-n =9600 g mol(-1), M-w=9800 g mol(-1), M-w/M-n = 1.1 for poly(ETCA); M-w = 14300gmol(-1)', M-w= 16200 gmol(-1) M-w/M-n= 1.2 for poly(ETCA-co-AA); M-n = 17900 gmol(-1), M-w = 18300 g mol(-1), M-w/M-n = 1.1 for poly(ETCA-co-VAc). The in vitro cytotoxicity of the synthesized compounds against mouse mammary carcinoma and human histiocytic lymphoma cancer cell lines decreased in the following order: 5-fluorouracil (5-FU) greater than or equal to ETCA > polymers. The in vivo antitumour activity of the polymers against Balb/C mice bearing sarcoma 180 tumour cells was greater than that of 5-FU at all doses tested. (C) 2001 Society of Chemical Industry.