A series of maleic anhydride (MA)–vinyl acetate (VA), MA–methyl methacrylate (MM) and MA–styrene (S) copolymers were prepared and characterized. By employing various amounts of initiator, MA–VA, MA–MM and MA–S copolymers with molecular weights ranging between 18 000 and 219 000 were obtained. The ‘in vivo’ and ‘in vitro’ tests performed on K562 cellular cultures (human chronic myeloid leukaemia) and also on Westar rats (inoculated with the Walker 256 carcinosarcome) showed that, as a function of the molecular weight, the copolymers synthesized had a 50% in vitro cytotoxicity and a mean tumour regression of a maximum of 68%. © 1997 SCI.

Three maleic anhydride copolymers [poly(maleic anhydride-vinyl acetate), poly(maleic anhydride-styrene) and poly(maleic anhydride-methyl methacrylate)] were prepared as well as the corresponding benzocaine conjugates. The maleic anhydride moiety was hydrolyzed to the corresponding polycarboxylate anions and then biologically evaluated using pyran copolymer as the standard. All of the polymers showed internal organ toxicity of the liver, kidneys and spleen which increased with increasing molecular weight, however, the benzocaine derivatives decreased this effect in most cases. The biological evaluations included hemoglobin levels, hematocrit levels, red blood indices and mean cell volumes which were increased on an average of 50%. The blood protein profiles were not changes significantly; on average they were changed about AE50%. The unmodified copolymers decreased the major serum and cholesterol levels by $75%. The copolymers (with or without) benzocaine decreased both the blood sugar and enzyme profiles. The antitumour activity was evaluated against Walker carcinosarconoma; although the benzocaine enhanced these effects, only pyran and the 18,000 Mw benzocaine-modified poly(maleic anhydride-vinyl acetate) produced significant effects.

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Cordycepin (3'-deoxyadenosine) is a potent anti-leukemic, anti-fungal, and anti-parasitic nucleoside antibiotic. Unfortunately, the biological activity of cordycepin is attenuated by its rapid conversion to 3'-deoxyinosine by adenosine deaminase (ADA). We have synthesized a series of ADA-resistant N-aminal and N-thioaminal cordycepin derivatives, which are protected from inactivation by deamination and yet retain biological activity. These compounds are hydrolyzed at various rates to efficiently release the parent drug cordycepin, and likely serve as simple hydrolytically activated prodrugs.