Relationship of molecular weight to antiviral and antitumor activities and toxic effects of maleic anhydride-divinyl ether (MVE) polyanions.
The molecular weight (MW) and dose dependency of several of the toxic effects and antitumor and antiviral activities of a new series of five maleic anhydride-divinyl ether copolymers (MVE) were established. Each polyanion preparation was relatively homogeneous and exhibited a narrow MW range, from 12,500 (MVE-1) to greater than 52,000 (MVE-5). All of the polyanions were effective as adjuvants to surgery against the metastatic Lewis lung carcinoma, and also exhibited marked antitumor activity against the P815 mastocytoma. MVE-1 retained antitumor activity while losing considerable antiviral activity. This polyanion also exhibited the least toxicity with regard to criteria such as sensitization to the lethal effects of endotoxin, inhibition of reticuloendothelial function, and depression of the microsomal mixed functional oxidase system. The MVE-4 (MW, 32,000) and MVE-5 (MW, 52,600) polyanions exhibited potent antitumor and antiviral activity, but also demonstrated dose-dependent toxic effects.
D000818:Animals; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004769:Enterovirus Infections / Q000188:drug therapy; D008175:Lung Neoplasms / Q000188:drug therapy; D008264:Macrophages / Q000276:immunology; D012515:Mast-Cell Sarcoma / Q000188:drug therapy; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects; D006899:Mixed Function Oxygenases / Q000378:metabolism; D008970:Molecular Weight; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D011108:Polymers / Q000494:pharmacology*; D011713:Pyran Copolymer / Q000494:pharmacology* / Q000633:toxicity
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D011108:Polymers; D011713:Pyran Copolymer; D006899:Mixed Function Oxygenases