Synthesis, enzymatic hydrolysis, and anti-HIV activity of AZT-spacer-curdlan sulfates

An AIDS (acquired immunodeficiency syndrome) drug, azidothymidine (AZT), was bound by an ester bond onto curdlan sulfate having both anti-HIV activity and the property of accumulating in lymphoid tissues to produce a series of biodegradable AZT-aliphatic-dicarboxylate-curdlan sulfates (designated as AZT-spacer-curdlan sulfates). When the carbon number of the alkylene group was 2-12, AZT-spacer-curdlan sulfates exhibited high anti-HIV activities in the EC50 range of 0.04-0.21 mu g/mL and low cytotoxicities of CC50 of more than 1000 mu g/mL. AZT-dodecanedicarboxylate-curdlan sulfate with the highest anti-HIV activity was easily hydrolyzed by esterase-enzymatic hydrolysis to release free AZT. Furthermore, an acidically released AZT from curdlan sulfate exhibited its high anti-HIV activity. AZT-dodecanedicarboxylate-curdlan sulfate showed a low anticoagulant activity of 7 unit/mg.