Activity of esterase in the hydrolysis of 3',5'-diesters of 5-fluoro-2'-deoxyuridine in relation to the structure of the diester prodrugs.

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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.
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