Initial studies on the mechanism of action of a new oncolytic thiazole nucleoside, 2-β-d-ribofuranosylthiazole-4-carboxamide NSC 286193)

Jayaram, Hiremagalur N.; Dion, Robert L.; Glazer, Robert I.; Johns, David G.; Robins, Roland K.; Srivastava, Prem C.; Cooney, David A.

doi:10.1016/0006-2952(82)90532-9

Cited by 149 publications

(51 citation statements)

References 8 publications

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“…7 TR is an inhibitor of IMPDH 8 and Phase I/II clinical trials conducted with this compound in acute myelogenous leukaemia patients, indicated a significant reduction in leukaemic cell burden.…”

Section: Introductionmentioning

confidence: 99%

Maintenance of ATP favours apoptosis over necrosis triggered by benzamide riboside

et al. 2002

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A new synthetic drug, benzamide riboside (BR) exhibited strong oncolytic activity against leukemic cells in the 5 ± 10 mM range. Higher BR-concentrations (20 mM) predominantly induced necrosis which correlated with DNA strand breaks and subsequent depletion of ATP-and dATP levels. Replenishment of the ATP pool by addition of adenosine prevented necrosis and favoured apoptosis. This effect was not a pecularity of BR-treatment, but was reproduced with high concentrations of all trans-retinoic acid (120 mM) and cyanide (20 mM). Glucose was also capable to suppress necrosis and to favour apoptosis of HL-60 cells, which had been treated with necrotic doses of BR and cyanide. Apoptosis eliminates unwanted cells without affecting the microenvironment, whereas necrosis causes severe inflammation of surrounding tissues due to spillage of cell fluids into the peri-cellular space. Thus, the monitoring and maintenance of cellular energy pools during therapeutic drug treatment may help to minimize nonspecific side effects and to improve attempted drug effects.

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Section: Introductionmentioning

confidence: 99%

Maintenance of ATP favours apoptosis over necrosis triggered by benzamide riboside

et al. 2002

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“…1669, Army Research Program on Antiparasitic Drugs. osyl-1,2,4-triazole-3-carboxamide) and that it has a significant activity against several experimental neoplasms, including those of the lung (15,18,26).…”

mentioning

confidence: 99%

Broad-spectrum antiviral activity of 2-beta-D-ribofuranosylselenazole-4-carboxamide, a new antiviral agent

Kirsi¹,

North²,

McKernan³

et al. 1983

Antimicrob Agents Chemother

155

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The relative in vitro antiviral activities of three related nucleoside carboxamides, ribavirin (1-3-D-ribofuranosyl-1,2,4-triazole-3-carboxamide), tiazofurin (2-3-D-ribofuranosylthiazole-4-carboxamide), and selenazole (2-p-D-ribofuranosylselenazole-4-carboxamide), were studied against selected DNA and RNA viruses. Although the activity of selenazole against different viruses varied, it was significantly more potent than ribavirin and tiazofurin against all tested representatives of the families Paramyxoviridae (parainfluenza virus type 3, mumps virus, measles virus), Reoviridae (reovirus type 3), Poxviridae (vaccinia virus), Herpesviridae (herpes simplex virus types 1 and 2), Togaviridae (Venezuelan equine encephalomyelitis virus, yellow fever virus, Japanese encephalitis virus), Bunyaviridae (Rift Valley fever virus, sandfly fever virus [strain Sicilian], Korean hemorrhagic fever virus), Arenaviridae (Pichinde virus), Picornaviridae (coxsackieviruses B1 and B4, echovirus type 6, encephalomyocarditis virus), Adenoviridae (adenovirus type 2), and Rhabdoviridae (vesicular stomatitis virus). The antiviral activity of selenazole was also cell line dependent, being greatest in HeLa, Vero-76, and Vero E6 cells. Selenazole was relatively nontoxic for Vero, Vero-76, Vero E6, and HeLa cells at concentrations of up to 1,000 ,g/ml. The relative plating efficiency at that concentration was over 90%. The effects of selenazole on viral replication were greatest when this agent was present at the time of viral infection. The removal of selenazole from the medium of infected cells did not reverse the antiviral effect against vaccinia virus, but there was a gradual resumption of viral replication in cells infected with parainfluenza type 3 or herpes simplex virus type 1 (strain KOS). However, the antiviral activity of ribavirin against the same viruses was reversible when the drig was removed.

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“…The enzymatic activity of IMPDH can be determined spectrophotometrically by monitoring the formation of NADH at 340 nm. Elevated type-II IMPDH levels have been found in ovarian tumors and leukemia cells [160]. The activity of IMPDH is tightly linked with cell proliferation and the inhibition of IMPDH has anticancer, antiviral, and immunosuppressive effects [161].…”

Section: Inosine 5′-phosphate Dehydrogenase (Impdh)mentioning

confidence: 99%

Mechanism Targeted Discovery of Antitumor Marine Natural Products

Nagle¹,

Zhou²,

Mora³

et al. 2004

Current Medicinal Chemistry

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Antitumor drug discovery programs aim to identify chemical entities for use in the treatment of cancer. Many strategies have been used to achieve this objective. Natural products have always played a major role in anticancer medicine and the unique metabolites produced by marine organisms have increasingly become major players in antitumor drug discovery. Rapid advances have occurred in the understanding of tumor biology and molecular medicine. New insights into mechanisms responsible for neoplastic disease are significantly changing the general philosophical approach towards cancer treatment. Recently identified molecular targets have created exciting new means for disrupting tumor-specific cell signaling, cell division, energy metabolism, gene expression, drug resistance, and blood supply. Such tumor-specific treatments could someday decrease our reliance on traditional cytotoxicity-based chemotherapy and provide new less toxic treatment options with significantly fewer side effects. Novel molecular targets and state-of-the-art molecular mechanism-based screening methods have revitalized antitumor research and these changes are becoming an ever-increasing component of modern antitumor marine natural products research. This review describes marine natural products identified using tumor-specific mechanism-based assays for regulators of angiogenesis, apoptosis, cell cycle, macromolecule synthesis, mitochondrial respiration, mitosis, multidrug efflux, and signal transduction. Special emphasis is placed on natural products directly discovered using molecular mechanism-based screening.

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Initial studies on the mechanism of action of a new oncolytic thiazole nucleoside, 2-β-d-ribofuranosylthiazole-4-carboxamide NSC 286193)

Cited by 149 publications

References 8 publications

Maintenance of ATP favours apoptosis over necrosis triggered by benzamide riboside

Maintenance of ATP favours apoptosis over necrosis triggered by benzamide riboside

Broad-spectrum antiviral activity of 2-beta-D-ribofuranosylselenazole-4-carboxamide, a new antiviral agent

Mechanism Targeted Discovery of Antitumor Marine Natural Products

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