Antitumor activity of 3?, 5?-diesters of 5-fluoro-2?-deoxyuridine against murine leukemia L1210 cells
- 1 July 1981
- journal article
- research article
- Published by Springer Nature in Cancer Chemotherapy and Pharmacology
- Vol. 6 (1) , 19-23
- https://doi.org/10.1007/bf00253005
Abstract
Summary Antitumor activity of several 3′,5′-diesters of 5-fluoro-2′-deoxyuridine (FUdR) against L1210 leukemia cells following intraperitoneal administration was examined. Esters of FUdR with aromatic acid or aliphatic acid of longer chain length were markedly active. Their activities, with respect to ILS30, were as much as 100 times that of unesterified FUdR. 3′,5′-ditoluoyl FUdR also had an improved therapeutic effect: its therapeutic ratio was increased to 8.1, as against 2.0 for FUdR. On the other hand, 3′,5′-diesters of FUdR with aliphatic acid of shorter chain length do not appear to be as active as FUdR. The relationship between the antitumor activity and plasma levels has also been examined. After 3′,5′-diacetyl FUdR, which is one of the drug group showing low cytotoxicity, the plasma concentration rapidly decreased to unmeasurable level 3 h after dosing. This tendency is similar to that shown in FUdR. On the other hand, with 3′,5′-dipalmitoyl FUdR and 3′,5′-dibenzoyl FUdR, each of which has a marked antitumor effect, plasma concentrations decreased slowly and were maintained for as long as 48 h after dosing. The results show that the cytotoxicity of diesters of FUdR is correlated with the duration of a high plasma level of FUdR.Keywords
This publication has 26 references indexed in Scilit:
- Differences between 5-fluoro-2′-deoxyuridine and 5-fluorouridine in their cytotoxic effect on growth of murine lymphoma L5178Y cells in in vivo and in vitro systemsPublished by Elsevier ,1980
- ON THE NATURE OF THYMINELESS DEATHAnnals of the New York Academy of Sciences, 1971
- Fluorinated pyrimidines. XXXIV. Structure-activity studies of methylated 5-fluoro-2'-deoxyuridine derivativesJournal of Medicinal Chemistry, 1970
- Infusion of fluorinated pyrimidines into hepatic artery for treatment of metastatic carcinoma of liverCancer, 1967
- Inhibition of thymidine phosphorylase by 6-aminothymine and derivatives of 6-aminouracilBiochemical Pharmacology, 1967
- 3′,5′-diesters of 5-fluoro-2′-deoxyuridine: Synthesis and biological activityBiochemical Pharmacology, 1965
- Fluorinated PyrimidinesProgress in Nucleic Acid Research and Molecular Biology, 1965
- Studies of Fluorinated Pyrimidines. XVIII. The Degradation of 5-Fluoro-2'-deoxyuridine and Related Compounds by Nucleoside Phosphorylase*Biochemistry, 1963
- Characterization of resistance to amethopterin, 8‐azaguanine and several fluorinated pyrimidines in the murine lymphocytic neoplasm, P388Journal of Cellular and Comparative Physiology, 1962
- Fluorinated Pyrimidines VI. Effects of 5-Fluorouridine and 5-Fluoro-2'-Deoxyuridine on Transplanted Tumors.Experimental Biology and Medicine, 1958