SYNTHESIS AND BIOLOGICAL-ACTIVITIES OF POLYMERS CONTAINING EXO-3,6-EPOXY-1,2,3,6-TETRAHYDROPHTHALIC GLYCINYLIMIDE

The monomer, exo-3,6-epoxy-1,2,3,6-tetrahydrophthalic glycinyl imide(E TGI), was prepared by the Diels-Alder reaction of N-glycinylmaleimide and furan. Poly(ETGI), poly(ETGI co-methacrylic acid)[poly(ETGI-co-MA) ] and poly(ETGI-co-vinylacetate) [poly(ETGI-co-VAc)] were synthesized by photoinitiated homopolymerization of ETGI or copolymerizations of E TGI with MA and VAc. Synthesized ETGI, poly(ETGI), poly(ETGI-co-MA), a nd poly(ETGI-co-VAc) were characterized by IR and H-1-NMR spectroscopi es, elemental anal ysis, and gel permeation chromatography. The in vit ro cytotoxicities of ETGI, poly(ETGI), poly(ETGI-co-MA), and poly(ETGI -co-VAc) were evaluated using K-562 human leukemia cells and HeLa cell s. In vitro cytotoxicity of monomer and polymers at a concentration of 1.0 mg/mL against K-562 human leukemia cells increased in the followi ng order: poly(ETGI co-MA) > poly(ETGI-co-VAc) > poly(ETGI) > ETGI. Th e cytotoxicities of copolymers against HeLa cells are less cytotoxic t han ETGI at a dosage of 0.02, 1.0, and 5.0 mg/mL. The copolymers were very effective at any dosage tested. The in vivo antitumor activities of ETGI, poly(ETGI), poly(ETGI-co-MA), and poly(ETGI-co-VAc) were also evaluated against mice bearing sarcoma 180. In vivo antitumor activit y of monomer and polymers at a dosage of 80 mg/kg increased in the fol lowing order: ETGI > poly(ETGI-co-VAc) > poly(ETGI-co-MA) > poly(ETGI) > 5-fluorouracil (5-FU). ETGI and polymers containing ETGI showed hig her antitumor activity than 5-FU at any dosage tested. (C) 1996 John W iley & Sons, Inc.