Synthesis and Properties of Novel Polyanions of Potential Antitumor Activity

A large number of naturally occurring polyanionic materials are known each of which possesses its own set of physiological properties. Within recent years, a wide variety of synthetic polyanions have become available, and investigators have compared their physiological properties with the naturally occurring polyanions. Perhaps, the most widely investigated synthetic polyanion is the 1:2 regularly alternating cycloco-polymer (DVE-MA) of divinyl ether (DVE) and maleic anhydride (MA), first discovered in these laboratories in 1951. This material 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 as well as other activities and is an interferon inducer. Many structural modifications of DVE-MA have been synthesized which also possess antitumor activity and interferon-inducing capability. A recent structural modification incorporated 5-fluorouracil (5-FU) into DVE-MA. This polymer is hydrolyzed readily to release 5-FU, and the material exhibited considerable activity against P388 lymphocytic leukemia. A novel series of polyanions have been synthesized via reactions of N-substituted triazolinediones with a variety of olefins and diene polymers. The synthesis and physiological properties of certain of these polyanions are discussed in this paper.