Syntheses and evaluations of antitumor and antiangiogenic phthalate polymers containing 5-fluorouracil and carboxylates.

New antitumor active polymers, poly(methacryloyl-2-oxy-1,2,3-propanetricarboxylic acid- co-exo-3,6-epoxy-1,2,3,6-tetrahydrophthalic acid) [poly(MTCA- co-ETAc)], poly(methacryloyl-2-oxy-1,2,3-propanetricarboxylic acid- co-hydrogen ethyl- exo-3,6-epoxy-1,2,3,6-tetrahydrophthalate) [poly(MTCA- co-HEET)], and poly (methacryloyl-2-oxy-1,2,3-propanetricarboxylic acid-co-a-ethoxy-exo-3,6-epoxy-1,2,3,6-tetrahydrophthaloyl-5-fluorouracil) [poly(MTCA-co-EETFU)] were synthesized and characterized. Their antitumor activity, inhibition of DNA replication and antiangiogenesis were examined. The structures of the polymers were identified by FT-IR,H andC-NMR spectroscopy. The number average molecular weights of the fractionated polymers determined by GPC ranged from 9,400 to 14,900, and polydispersity indices were less than 1.7. The in vitro cytotoxicity of these polymers was determined and their antitumor activity was evaluated. The IC values (the drug concentration at inhibition of 50% tumor growth) indicated that the synthesized polymers were much better inhibitors of cancer cells and showed lower cytotoxicity than the free 5-FU. The in vivo antitumor activity of the conjugates was examined using mice bearing the sarcoma 180 tumor cell line. The life spans (T/C) of the mice treated with the conjugates were higher than those treated with the free 5-FU. In addition, the synthesized conjugates showed excellent antiangiogenic activity based on an embryo chorioallantoic membrane assay. [ABSTRACT FROM AUTHOR]