Quantitative Studies in Chemotherapy: I. The Trypanocidal Action of Arsenic and Antimony Compounds

Voegtlin, Carl; Smith, Homer W.; Crane, Marian M.; Wright, Katherine D.; Connell, Mabel A.

doi:10.2307/4575729

Cited by 9 publications

(4 citation statements)

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“…One key chemical characteristic of arsenic is the ease with which pentavalent and trivalent arsenicals can interconvert (5, 37,47,48). It has long been known that trivalent arsenicals are in general much more active than their pentavalent counterparts (49), for instance, as enzyme inhibitors (33), cytotoxins (32,34,41), genotoxins (26,35,44,50,51), and clastogens (35). This generalization may be applicable to more complex arsenicals such as arsenosugars.…”

Section: Discussionmentioning

confidence: 99%

Do Arsenosugars Pose a Risk to Human Health? The Comparative Toxicities of a Trivalent and Pentavalent Arsenosugar

Andrewes

DeMarini

Funasaka

et al. 2004

Environ. Sci. Technol.

105

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Seafood frequently contains high concentrations of arsenic (approximately 10-100 mg/kg dry weight). In marine algae (seaweed), this arsenic occurs predominantly as ribose derivatives known collectively as arsenosugars. Although it is clear that arsenosugars are not acutely toxic, there is a possibility of arsenosugars having slight chronic toxicity. In general, trivalent arsenicals are more toxic than their pentavalent counterparts, so in this work we examine the hypothesis that trivalent arsenosugars might be significantly more toxic than pentavalent arsenosugars in vitro. We compared the in vitro toxicity of (R)-2,3-dihydroxypropyl-5-deoxy-5-dimethylarsinoyl-beta-D-riboside, a pentavalent arsenosugar, to that of its trivalent counterpart, (R)-2,3-dihydroxypropyl-5-deoxy-5-dimethylarsino-beta-D-riboside. The trivalent arsenosugar nicked plasmid DNA, whereas the pentavalent arsenosugar did not. The trivalent arsenosugar was more cytotoxic (IC50 = 200 microM, 48 h exposure) than its pentavalent counterpart (IC50 > 6000 microM, 48 h exposure) in normal human epidermal keratinocytes in vitro as determined via the neutral red uptake assay. However, both the trivalent and the pentavalent arsenosugars were significantly less toxic than MMA(III), DMA(III), and arsenate. Neither the pentavalent arsenosugar nor the trivalent arsenosugar were mutagenic in Salmonella TA104. The trivalent arsenosugar was readily formed by reaction of the pentavalent arsenosugar with thiol compounds, including, cysteine, glutathione, and dithioerythritol. This work suggests that the reduction of pentavalent arsenosugars to trivalent arsenosugars in biology might have environmental consequences, especially because seaweed consumption is a significant environmental source for human exposure to arsenicals.

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Section: Discussionmentioning

confidence: 99%

Do Arsenosugars Pose a Risk to Human Health? The Comparative Toxicities of a Trivalent and Pentavalent Arsenosugar

Andrewes

DeMarini

Funasaka

et al. 2004

Environ. Sci. Technol.

105

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“…Again this seems probable. Voegtlin and Smith have shown that pentavalent arsenicals undergo reduction in vivo before exerting their trypanocidal effects (42). It has also been shown that such activation can occur even by incubation of pentavalent arsenicals with blood in vitro (43).…”

Section: Discussionmentioning

confidence: 99%

The Anticoagulant and Antilymphoma Properties of Arsenic Azoproteins

Broome

Kidd

1964

The Journal of Experimental Medicine

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Experiments here given show that 4-arsonophenylazoproteins form complexes with fibrinogen which are resistant to the enzymic action of thrombin, coagulation being thus inhibited; also that arsenic azoproteins combine strongly with polymerizing fibrin, the reaction leading uniquely to acceleration of the process. Ordinary arsenicals have little or no effect on the proliferation of Lymphoma 6C3HED cells in vivo. 4-Arsonophenylazoproteins, by contrast, are strongly inhibitory, and they arrest the process of mitosis in metaphase, as does colchicine. Considered together with the observations of the preceding paper, the findings suggest that 4-arsonophenylazoproteins may exert their anticoagulant and antilymphoma effects by similar or related means: in the former instance, by combining in vitro with fibrinogen and polymerizing fibrin, thus altering the clotting process as mentioned above; and in the latter instance by combining, perhaps in a similar way, with polymerizing proteins in the mitotic spindle of proliferating Lymphoma 6C3HED cells, thus arresting mitosis. Further implications of the findings are discussed.

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“…He introduced salvarsan for the treatment of syphilis. Salvarsan is oxidized in vivo to 3-amino-4-hydroxyphenyl arsenoxide, the actual therapeutic agent ( Figure 5-3) (Voegtlin and Smith, 1920). The arsenoxide covalently binds to SH groups essential for survival of the spirochete.…”

Section: Metal Chelationmentioning

confidence: 99%

Thiols, Disulfides, and Thioesters

Huxtable

1986

Biochemistry of Sulfur

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Quantitative Studies in Chemotherapy: I. The Trypanocidal Action of Arsenic and Antimony Compounds

Cited by 9 publications

References 0 publications

Do Arsenosugars Pose a Risk to Human Health? The Comparative Toxicities of a Trivalent and Pentavalent Arsenosugar

Do Arsenosugars Pose a Risk to Human Health? The Comparative Toxicities of a Trivalent and Pentavalent Arsenosugar

The Anticoagulant and Antilymphoma Properties of Arsenic Azoproteins

Thiols, Disulfides, and Thioesters

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