Synthesis and biological activity of phthalimide‐based polymers containing 5‐fluorouracil

Abstract

The attachment of anticancer agents to polymers is a promising approach towards reducing the toxic side‐effects and retaining the potent antitumour activity of these agents. A new tetrahydrophthalimido monomer containing 5‐fluorouracil (ETPFU) and its homopolymer and copolymers with acrylic acid (AA) and with vinyl acetate (VAc) have been synthesized and spectroscopically characterized. The ETPFU contents in poly(ETPFU‐co‐AA) and poly(ETPFU‐co‐VAc) obtained by elemental analysis were 21 mol% and 20 mol%, respectively. The average molecular weights of the polymers determined by gel permeation chromatography were as follows: Mn = 8900 g mol−1, Mw = 13 300 g mol−1, Mw/Mn = 1.5 for poly(ETPFU); Mn = 13 500 g mol−1, Mw = 16 600 g mol−1, Mw/Mn = 1.2 for poly(ETPFU‐co‐AA); Mn = 8300 g mol−1, Mw = 11 600 g mol−1, Mw/Mn = 1.4 poly(ETPFU‐co‐VAc). The in vitro cytotoxicity of the compounds against FM3A and U937 cancer cell lines increased in the following order: ETPFU > 5‐FU > poly(ETPFU) > poly(ETPFU‐co‐AA) > poly(ETPFU‐co‐VAc). The in vivo antitumour activities of all the polymers in Balb/C mice bearing the sarcoma 180 tumour cell line were greater than those of 5‐FU and monomer at the highest dose (800 mg kg−1). © 2002 Society of Chemical Industry

Synthesis and Characterization of a Novel PAA Carrier for Apitoxin of Apis mellifera L.

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Exchange reactions of poly‐2‐(N‐phthalimido)ethyl acrylate with hydroxy and amino compounds

“…Recently, several activated polymers, containing phthalimido moiety, have been used as macromolecular drugs. [1][2][3][4] One of the most interesting topics in the field of pharmacologically active polymers is the preparation of polymeric drugs, in which drugs are attached to the polymeric backbone via covalent bonds with limited stability to biological environments. 5,6 Activated esters of acrylic and methacrylic acids may be used as precursors of some classes of multifunctional polymers.…”

Synthesis and antitumour activity of medium molecular weight phthalimide polymers of camptothecin

“…Such polymers have been found in our laboratories to be efficient carriers of 5‐fluorouracil (5‐FU), retaining the antitumour activity while decreasing the toxicity of the parent molecule. Moreover, tetrahydrophthalic‐acid‐based polymers showed a strong antitumour activity against cancer cell lines,21–24 while they displayed very low toxicity against normal cells 25…”