Mechanisms of Resistance to Anticancer Agents

Rw, Brockman

doi:10.1016/s0065-230x(08)60983-5

Cited by 143 publications

(33 citation statements)

References 451 publications

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“…Iron chelators by affecting intracellular and extracellular iron transport and storage may inhibit DNA synthesis and other metabolic processes dependent on iron [2,4,5]. A direct effect on the iron-dependent enzyme ribonucleotide reductase has been shown in a cell free system [6], and has been postulated in the intact cell [7,8]. Effective iron chelators like desferrioxamine may inhibit the toxicity of iron in vitro, but less effective ones like EDTA may exacerbate its toxic effects [9,10] Desferrioxamine has been reported to inhibit DNA synthesis in a variety of cell culture systems, although the effect has only been seen at high drug concentrations or with prolonged exposure of the cells to the drug [ 1 l-131.…”

Section: Introductionmentioning

confidence: 99%

“…Effective iron chelators like desferrioxamine may inhibit the toxicity of iron in vitro, but less effective ones like EDTA may exacerbate its toxic effects [9,10] Desferrioxamine has been reported to inhibit DNA synthesis in a variety of cell culture systems, although the effect has only been seen at high drug concentrations or with prolonged exposure of the cells to the drug [ 1 l-131. Other potential iron chelating drugs may be more effective in inhibiting DNA synthesis [7,11], and some have been reported to be cytotoxic [ 11,14,15]. …”

Section: Introductionmentioning

confidence: 99%

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Cytotoxic effects of the lipophilic iron chelator omadine

1986

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Cytotoxic effects were observed following 4 h incubation of human leukaemic cells with the iron chelator 1‐hydroxypyridine‐2‐thione (omadine). Its Cytotoxic activity was comparable to that of the cytotoxic drug doxorubicin. At the same concentration two other effective iron chelators, desferrioxamine and 1,2‐dimethyl‐3‐hydroxypyrid‐4‐one, were not cytotoxic. Addition of iron augmented the effect of omadine. It is suggested that the lipophilic properties of omadine and of its iron complex cause their intracellular accumulation and potent cytotoxic activity.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cytotoxic effects of the lipophilic iron chelator omadine

1986

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“…First, since it has been reported that cAMP and the 3', 5'-cyclic phosphate of 9-fl-D-arabinofuranosyladenine may cross cell membranes (9,13,14), the possibility of other cyclic nucleotides having this property appears to be reasonable. Hence, assuming the compounds are acting at the 5'-mono-, di-, or triphosphate level in the cell, as do other purine and pyrimidine nucleosides (1,2,5,7,21), little additional alteration of the molecule would be required by the host system. Meyer et al (10) have shown that hydrolysis of these compounds by the ubiquitous cyclic nucleotide phosphodiesterase is necessary to produce the 5'-monophosphate.…”

Section: Resultsmentioning

confidence: 99%

In Vitro Antiviral Activity of 6-Substituted 9-β- d -Ribofuranosylpurine 3′,5′-Cyclic Phosphates

Sidwell¹,

Huffman²,

Allen³

et al. 1974

Antimicrob Agents Chemother

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A series of twelve recently synthesized 6-substituted derivatives of 9-β- d -ribofuranosylpurine 3′,5′-cyclic phosphate (RPcMP) were evaluated for in vitro antiviral activity, using inhibition of viral cytopathogenic effect as the primary parameter for evaluation. Inhibition of the development of intra- and extracellular virus titer was used as a secondary criterion with certain viruses. Five derivatives were considered to have significant antiviral activity. 6-Hydroxylamino-RPcMP was active against type 1 herpes simplex, cytomegalo-, and vaccinia viruses. 6-Thio-RPcMP was inhibitory to types 1 and 2 herpes simplex, cytomegalo-, vaccinia, and type 3 parainfluenza viruses. The 6-methylthio derivative was active against types 1 and 2 herpes simplex, cytomegalo-, and vaccinia viruses, and types 1A, 2, 8, and 13 rhinoviruses; alteration of this 6-substitution to 6-ethylthio or to 6-benzylthio weakened the herpes- and vaccinia virus activity of the compound, but each continued to have significant antirhinovirus activity. The effect of time of addition of 6-methylthio-RPcMP to type 1 herpes simplex virus-infected cells was determined; the compound was most active when added prior to the virus. Early removal of the compound from the infected cells markedly reduced its antiviral effectiveness.

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“…On a biochemical level, this inhibition of mitosis has been mediated through a nucleic acid mechanism. Thus in the case of the alkylating agents (32), the antipurines (33), and the folic acid antagonists (34), inhibition of DNA synthesis appears to be responsible for the inhibition of mitosis, although an RNA mechanism has not been ruled out. The mechanism of action of actinomycin D is probably through DNA-dependent RNA synthesis (35).…”

Section: Immune Suppression By Vincristine and Vinblastinementioning

confidence: 99%