The potential of aspirin in prodrug synthesis: a new potential delivery system of AZT and FLT

Aspirin (O-acetylsalicylic acid) has been used to synthesize prodrugs of 3'-azido-3'-deoxythymidine (AZT) and 3'-deoxy-3'-fluorothymidine (FLT). The mixed anhydride between aspirin and trifluoroacetic acid was synthesized and reacted with AZT and FLT to give the blocked nucleosides attached through the 5'-O position to the 2-position of 2-methyl-4H-1,3-benzodioxin-4-one. The prodrugs showed the same activities against HIV-1 in MT-4 cells as the original drugs. Hydrolysis of the synthesized prodrugs in the growth medium, used for anti-HIV investigations, resulted in formation of 5-O acetylated drugs which were subsequently hydrolyzed into the original drugs.