Synthesis of Vinyl Polymer by Fixing 5-Fluorouracils through Organosilicon Groups via Carbamoyl Bonds and Its Antitumor Activity

Abstract

Some vinyl polymers by fixing 5FUs via carbamoyl bonds on organosilicon groups were synthesized by means of ordinary radical polymerization of the corresponding monomers. These hybrid type vinyl polymers with 5FU and or ganosilicon amine units exhibited significant antitumor activities against p-388 lymphocytic leukemia in mice in vivo (i.p./i.p.). The effects of the molecu lar weight, the hydrophobicity of the polymer carrier, the number of methy lenes in the spacer group, and the presence of silicon on the antitumor activity were investigated. The low molecular weight homopolymer of 5-fluoro-3,4-dihy dro-2,4-dioxo-N-(4,4-dimethyl-4-silahex-5-enyl)-1-(2H)-pyrimidinecarboxamide (KY20), Poly(KY-20), and the copolymer of KY-20 with 2-hydroxyethylmeth acrylate, Poly(KY-20/HEMA), exhibited especially high antitumor activities. The polymers obtained did not display an acute toxicity in the dose range of 25-800 mg/kg. Thus, these polymers were suggested to act as macromolecular prodrugs of 5FU.

Synthesis, Hydrolysis, and Antitumor Activity of Conjugates of 5-Fluorouracil with Poly(L-lysine)

“…Ouchi 15 reported that carbamoyl bonds in the conjugates of 5FU and vinyl polymeric carriers could be perfectly hydrolyzed by refluxing in 5 N NaOH aq. soln.…”