Synthesis and antitumour and antiangiogenesis activity of polymers containing methacryloyl-2-oxy-1,2,3-propane tricarboxylic acid

A new monomer, methacryloyl-2-oxy-1,2,3-propane tricarboxylic acid (MTCA), was synthesized from citric acid and methacrylic anhydride. Poly(methacrylo yl-2-oxy-1,2,3-propane tricarboxylic acid) and poly(methacryloyl-2-oxy-1,2, 3-propane tricarboxylic acid)-co-(maleic anhydride) were prepared by radica l polymerizations. Terpoly(methacryloyl-2-oxy-1,2,3-propane tricarboxylic a cid-maleic anhydride-furan) was obtained by in situ terpolymerization of MT CA and exo-3,6-epoxy-1,2,3,6-tetrahydrophthalic anhydride. The synthesized samples were identified by FTIR, H-1 NMR and C-13 NMR spectroscopies. The n umber-average molecular weights of the fractionated polymers determined by GPC were in the range 14900-16600 and polydispersity indices were less than 1.14. The in vitro IC50 values of the monomer and polymers against cancer and normal cell lines were much higher than those of 5-fluorouracil (5-FU). The in vivo antitumour activities of the synthesized samples at a dosage o f 0.8 mg kg(-l) against mice bearing the sarcoma 180 tumour cell line decre ased in the order terpoly(MTCA-MAH-FUR) > poly(MTCA-co-MAH) > poly(MTCA) > MTCA > 5-FU. The synthesized samples inhibited DNA replication and angiogen etic activity more than did 5-FU. (C) 2001 Society of Chemical Industry.