Synthesis, Enzymatic Hydrolysis, and Anti-HIV Activity of AZT−Spacer−Curdlan Sulfates

Abstract

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 μg/mL and low cytotoxicities of CC50 of more than 1000 μg/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.