SYNTHESIS AND BIOLOGICAL-ACTIVITIES OF ENDO-3,6-EPOXY-1,2,3,6-TETRAHYDROPHTHALIMIDE AND ITS POLYMERS

Photocopolymerizations of endo-3,6-epoxy-1,2,3,6-tetrahydrophthalimide (ETPI) with acrylic acid (AA), vinyl acetate (VAc), and maleic anhydr ide (MAH) were carried out in a mixed solvent of 2-butanone and aceton e using 2,2-dimethoxy-2-phenylacetophenone as an initiator at 25 degre es C. Synthesized ETPI, poly(ETPI), poly(ETPI-co-AA), poly(ETPI-co-VAc ), and poly(ETPI-co-MAH) were characterized by IR and H-1-NMR spectros copies, elemental analysis, and gel permeation chromatography. The syn thesized polymers have a number-average molecular weight ((M) over bar (n)) in the range of 3500-27,400. The in vitro cytotoxicities of poly( ETPI), poly(ETPI-co-AA), poly(ETPI-co-VAc), and poly(ETPI-co-MAH) agai nst fibroblast and K-562 human leukemia cells were lower than that of monomeric ETPI at a low concentration (0.02 mg/mL). The in vivo antitu mor activities of the polymers were evaluated by the survival time wit h sarcoma 180 tumor-bearing mice. The polymers showed higher antitumor activity and lower toxicity than both monomeric ETPI and 5-fluorourac il at all doses tested. (C) 1997 John Wiley & Sons, Inc.