BIOCHEMISTRY AND BIOLOGICAL EFFECTS OF THE PYRAZOFURINS<sup>*</sup> (PYRAZOMYCINS): INITIAL CLINICAL TRIAL

Gutowski, Gerald E.; Sweeney, Martin J.; DeLong, Donald C.; Hamill, Robert L.; Gerzon, Koert; Dyke, Richard W.

doi:10.1111/j.1749-6632.1975.tb29257.x

Cited by 107 publications

(44 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results indicate that at its fully effective concentration (1 jiM) pyrazofurin depressed UTP and CTP pools to 20 and 25%, respectively, of the concentrations found in untreated cancer cells. These results further support the postulate for a primary ac tion of pyrazofurin as an inhibitor of pyrimidine bio synthesis [1,21,22]. On the basis of such tissue culture investigations, in vivo combinations with galac tosamine were worked out and the selective action of this combination treatment on hepatomas was tested.…”

Section: Effect O F Pyrazofurin On Ribonucleotide Pattern Of Cancer Csupporting

confidence: 52%

“…Pyrazofurin is a C-nucleoside that in its phosphorylated form can act as a competitive inhibitor of OMP decarboxylase and thus function as a blocker of de novo UMP biosynthesis [1]. Table VI shows a doseresponse study where the action of pyrazofurin on tumor cell growth is contrasted with the behavior of the concentrations of purine and pyrimidine nucleo side triphosphates.…”

Section: Effect O F Pyrazofurin On Ribonucleotide Pattern Of Cancer Cmentioning

confidence: 99%

See 1 more Smart Citation

Recent Advances in the Design of Anticancer Chemotherapy

Weber¹

1980

Oncology

View full text Add to dashboard Cite

Recent advances in the rational design of anticancer chemotherapy in this laboratory have been based on strategic differences between normal and cancer cells. On the basis of our identification of quantitative biochemical markers and characteristic enzymic and metabolic programs of neoplastic cells, we have designed single and combination drug treatments. This chemotherapeutic approach aims at specific enzymic targets in cancer cells that are closely linked with transformation and progression. With the identification of markedly increased concentrations of CTP, dATP, dGTP, dCTP and dTTP in neoplasms, there should be an operational advantage in directing chemotherapy to depress the concentration of these metabolites elevated in cancer cells, because a drug-imposed curtailment of these metabolites might destroy cancer cells that depend more stringently on the increased concentrations of these nucleotides. Experiments in tissue culture and in solid tumors utilizing treatment schedules with pyrazofurin in combination with galactosamine, and the use of adriamycin, succeeded in achieving profound alterations in the nucleotide concentrations of cancer cells.

show abstract

Section: Effect O F Pyrazofurin On Ribonucleotide Pattern Of Cancer Csupporting

confidence: 52%

Section: Effect O F Pyrazofurin On Ribonucleotide Pattern Of Cancer Cmentioning

confidence: 99%

Recent Advances in the Design of Anticancer Chemotherapy

Weber¹

1980

Oncology

View full text Add to dashboard Cite

show abstract

“…It has previously been reported to exhibit both antitumor and antiviral properties (7,12,36). In the present study, pyrazofurin exhibited a marked inhibitory effect on RSV replication at a rather low concentration.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effects of antiviral compounds on respiratory syncytial virus replication in vitro

Kawana¹,

Shigeta²,

Suzuki³

et al. 1987

Antimicrob Agents Chemother

View full text Add to dashboard Cite

We examined the inhibitory effect of 20 antiviral compounds, including ribavirin, on the replication of respiratory syncytial virus in HeLa and HEp-2 cell cultures. Of the compounds studied, pyrazofurin and 3-deazaguanine emerged as more potent inhibitors of respiratory syncytial virus than ribavirin. Based on their inhibitory effect on the cytopathogenicity of respiratory syncytial virus in HeLa cells, the average 50% effective dose of pyrazofurin and 3-deazaguanine for eight strains was 0.07 and 1.65 ,ug/ml, respectively; that of ribavirin was 5.82 p.g/ml. The cytotoxicity of these compounds for HeLa cells was examined by monitoring the incorporation of radiolabeled uridine into cellular RNA. The selectivity indexes of pyrazofurin and 3-deazaguanine exceeded that of ribavirin by 70-and 11-fold, respectively. Pyrazofurin, 3-deazaguanine, and ribavirin inhibited both viral antigen expression and syncytium formation in HeLa cell cultures, as assessed by an indirect immunofluorescence assay. In these assays, pyrazofurin and 3-deazaguanine again proved more potent than ribavirin. 2,5-Diamidinoindole and carbodine were less potent than ribavirin. Various other compounds, i.e., 3-adenin-9-yl-2-hydroxypropanoic acid isobutyl ester, 3-deazauridine, 3'-C-methyluridine, 5'-deoxy-5-fluorouridine, 5-cyanoimidazole-4-carboxamide, and its ribofuranosyl derivative, did not inhibit the cytopathic effect of the Long strain of respiratory syncytial virus at concentrations -125 pLg/ml. Tubercidin, 5-chlorotubercidin, xylotubercidin, neplanocin A, thiosemicarbazone R, and 3-methylquercetine were too toxic to HeLa cells for their inhibitory effects on respiratory syncytial virus to be examined.Respiratory syncytial virus (RSV) causes lower respiratory tract infections such as bronchiolitis and pneumonia in infancy and early childhood. Most clinicians consider RSV one of the most important agents of acute respiratory disease in children, and almost 50% of infants are expected to suffer from RSV infection during their first winter (15,16,20,32,35). Inactivated RSV vaccine does not protect against natural infection and leads to an unusual immune response and even lung inflammation during the course of a subsequent natural infection (21). Recent research efforts have therefore focused on the development of either potent live RSV vaccines or effective antiviral compounds.Following reports that ribavirin may reduce the severity of illness and amount of virus shed in acute respiratory infections due to RSV or influenza B virus (13,14,23,37), the drug has been approved in aerosol form for the chemotherapy of RSV infections. This has prompted the search for antiviral compounds that may be as effective, if not more effective, against RSV than ribavirin. We have now investigated the inhibitory effects of 20 antiviral compounds, including ribavirin, on the replication of RSV in vitro.MATERIALS AND METHODS Viruses. The Long, S-2, and S-8 strains of RSV were kindly provided by Y. Numazaki, National Sendai Hospital, Sendai, Japan. The 58-8, 58-7,...

show abstract

“…This in vivo toxicity also hampered the further evaluation of pyrazofurin against murine leukemia virus, which, like VSV, appeared exquisitely sensitive (MIC: 0.01 µg/ml) to inhibition by pyrazofurin (59). Pyrazofurin (originally named pyrazomycin) has since long been shown to inhibit de novo pyrimidine mononucleotide biosynthesis at the level of orotidylic acid (OMP) decarboxylase (which converts OMP to UMP) (60,61).…”

Section: Bcx4430 (Fig 7)mentioning

confidence: 99%

Vesicular stomatitis virus (VSV) as a paradigm for predicting antiviral activity against Ebola virus (EBOV)

Clercq

2015

mpj

View full text Add to dashboard Cite

There are at present no antivirals available which have been formally licensed for clinical use for the treatment of Ebola virus (EBOV) infections in humans. The most advanced to be approved for this purpose is favipiravir (T-705), a viral RNA polymerase inhibitor. Under consideration are BCX4430, also a viral RNA polymerase inhibitor, and 3-deazaneplanocin A and various other S-adenosylhomocysteine (SAH) hydrolase inhibitors. A number of compounds which have been approved for other purposes seem to interact with the cell entry of EBOV. Some compounds like pyrazofurin have been found to be exquisitely potent inhibitors of vesicular stomatitis virus (VSV). VSV belongs to the rhabdoviridae, a family closely related to the family of the filoviridae to which EBOV and Marburg virus belong. VSV, unlike EBOV and Marburg virus which require biosafety level 4, can be handled in conventional safety conditions.

show abstract

BIOCHEMISTRY AND BIOLOGICAL EFFECTS OF THE PYRAZOFURINS^* (PYRAZOMYCINS): INITIAL CLINICAL TRIAL

Cited by 107 publications

References 8 publications

Recent Advances in the Design of Anticancer Chemotherapy

Recent Advances in the Design of Anticancer Chemotherapy

Inhibitory effects of antiviral compounds on respiratory syncytial virus replication in vitro

Vesicular stomatitis virus (VSV) as a paradigm for predicting antiviral activity against Ebola virus (EBOV)

Contact Info

Product

Resources

About

BIOCHEMISTRY AND BIOLOGICAL EFFECTS OF THE PYRAZOFURINS* (PYRAZOMYCINS): INITIAL CLINICAL TRIAL

Cited by 107 publications

References 8 publications

Recent Advances in the Design of Anticancer Chemotherapy

Recent Advances in the Design of Anticancer Chemotherapy

Inhibitory effects of antiviral compounds on respiratory syncytial virus replication in vitro

Vesicular stomatitis virus (VSV) as a paradigm for predicting antiviral activity against Ebola virus (EBOV)

Contact Info

Product

Resources

About

BIOCHEMISTRY AND BIOLOGICAL EFFECTS OF THE PYRAZOFURINS^* (PYRAZOMYCINS): INITIAL CLINICAL TRIAL