Potential radiosensitizing antiviral and anticancer pyrimidine nucleosides. Technical progress report, June 1, 1975--December 22, 1975. [UV radiation]
A newly developed method of synthesis now affords the large scale production of 5'-amino analogs of a variety of nucleosides. This procedure has been used to synthesize the 5'-amino analog of 5-iodo-, 5-bromo-, 5-chloro-, 5-fluoro-, 5-trifluoromethyl-2',5'-dideoxyuridine. In addition to the previously established antiviral activity of 5-iodo-5'-amino-2',5'-dideoxyuridine (AIU), we have found 5-bromo- (ABrU) and 5-iodo-5'-amino-2',5'-dideoxycytidine (AIC) to be even more potent antiviral agents than AIU both in vitro and of AIC against experimental herpatic keratitis in rabbits. Initial studies indicate a non-toxicity in vitro. There is sound reason to predict AIC and ABrC to each have a broader spectrum of antiviral activity than AIU and to have a similar lack of toxicity. 5-Fluoro- as well as 5-trifluoromethyl-5'-amino-2',5'-dideoxyuridine, and 5'-amino arabinosyl cytosine (A-ara C) have antiviral activity which is less potent than the parent compound, but each has a vastly improved therapeutic index. Additional experiments have been performed with experimental herpetic keratitis which confirm that AIU has similar efficacy but less potency than iododeoxyuridine, however the favorable therapeutic index of AIU should make it a preferable agent. Metabolic studies show AIU to be incorporated into the DNA of only cells infected with herpes simplex virus (HSV) type 1, and to be phosphorylated by a cell-free extract from only HSV infected cells. These findings explain the complete lack of toxicity to the uninfected cell whether in vitro or in vivo.
- Research Organization:
- Yale Univ., New Haven, Conn. (USA). School of Medicine
- OSTI ID:
- 7350788
- Report Number(s):
- COO-2468-2
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
560111 -- Radiation Effects on Biochemicals-- In Vitro-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
ANTIMETABOLITES
ANTIMITOTIC DRUGS
AZINES
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BIOSYNTHESIS
BROMOURACILS
BUDR
DISEASES
DNA
DRUGS
ELECTROMAGNETIC RADIATION
ENZYMES
FLUOROURACILS
FUDR
HERPES SIMPLEX
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INFECTIOUS DISEASES
IODODEOXYURIDINE
IODOURACILS
MAMMALS
METABOLISM
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC BROMINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC FLUORINE COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC IODINE COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHOSPHOTRANSFERASES
PYRIMIDINES
RABBITS
RADIATION EFFECTS
RADIATIONS
RADIOSENSITIVITY EFFECTS
RADIOSENSITIZERS
RESPONSE MODIFYING FACTORS
RIBOSIDES
SKIN DISEASES
SYNTHESIS
THERAPY
TOXICITY
TRANSFERASES
ULTRAVIOLET RADIATION
URACILS
VERTEBRATES