Synthesis and properties of alternating copolymers of potential antitumor activity containing 5‐fluorouracil

Abstract

Abstract“Pyran” copolymer, the 2:1 regularly alternating cyclocopolymer (DVE—MA) of maleic anhydride (MA) and divinyl ether (DVE), first discovered in 1951, has been investigated extensively, both from the standpoint of its chemical structure and its biological activity. Although certain aspects of its structure remain to be determined, it has been shown to possess a wide spectrum of biological activity. It possesses antitumor activity and has been investigated clinically. During the clinical investigation, it was found to be an interferon inducer. Interferon is a protein which appears to be the body's first line of defense against viral infection. DVE—MA also possesses antiviral, antibacterial, antifungal, antiarthritic, and anticoagulant properties, activates macrophages, inhibits reverse transcriptase, and is capable of elimination of Pu. During the course of investigations in these laboratories, many structural modifications of DVE—MA have been made. Many of these modifications also possess considerable antitumor activity and interferon‐induction capability. Perhaps the most interesting structural modification has been the incorporation of 5‐fluorouracil (5‐FU) into the polymer (NSC 255083). This polymer has shown (T/C)% [= ratio of test (T) to control (C) survival times] = 189 for dose by intraperitoneal injection of 200 mg/kg animal weight in CD2F1 mice (6/6 survivors after fifth day) against P388 lymphocytic leukemia. This article describes the synthesis of both the monomer and copolymer, and a study of the hydrolytic rate of release of 5‐FU from the polymer.