Activity of Esterase in the Hydrolysis of 3',5'-Diesters of 5-F1uoro-2'-deoxyuridine in Relation to the Structure of the Diester Prodrugs

Abstract

The activity of porcine liver esterase towards diesters of 5-fluoro-2'-deoxyuridine with saturated aliphatic acids including acetic, propionic, butyric, hexanoic, octanoic, decanoic and dodecanoic acids was investigated. The susceptibility of the 3 ',5 '-diesters increased as the acyl chain was lengthened up to octanoyl, but further increase in the acyl chain length resulted in a sharp decrease in the susceptibility. The susceptibility of 3'- and 5'-monoesters increased as the chain was lengthened to decanoyl and slightly decreased on going to dodecanoyl. These results suggest that the higher antitumor activity of longer alkyl chain diesters of 5-fluoro-2'-deoxyuridine is partly due to their slow rates of hydrolysis by non-specific esterase. © 1985, The Pharmaceutical Society of Japan. All rights reserved.