Y. Nishizawa, J. Casida
Nov 1, 1965
Citations
0
Influential Citations
39
Citations
Quality indicators
Journal
Biochemical pharmacology
Abstract
Abstract Twenty-seven esters of 5-fluoro-2′-deoxyuridine (FUDR) were prepared and their toxicity and/or carcinostatic activity assayed by oral administration to mice with adenocarcinoma-755 tumors. 3′,5′-Diesters of FUDR with C 4 to C 16 aliphatic acids had a greater effect on the mice or the tumors than equivalent dosages of unesterified FUDR. The dibutyryl, dihexanoyl, and dioctanoyl were the most effective antitumor agents of the FUDR diesters with aliphatic acids. Carboxylic diesters with nonaliphatic acids, and certain sulfonyl, carbamoyl, and phosphoryl esters, offered no distinct advantage over the aliphatic esters, owing to either low carcinostatic activity or high toxicity. The toxicity and possibly also the antitumor potency of 3′,5′-dibutyryl FUDR were increased by simultaneous administration of an organophosphate inhibitor for esterases, effecting its hydrolysis. 3′,5′-Dibutyryl thymidine also increased the toxicity of FUDR to mice. The FUDR esters were less potent than FUDR in inhibiting the reproductive potential of houseflies and pea aphids.