Pharmacokinetics of Two Spiroarsoranes Administered Intravenously or Orally to Rabbits

Rekik, L.; Coulais, Yvon; Rochas, M.A.; Campistron, G.; Wolf, J. G.; Houin, Georges

doi:10.1002/jps.2600780306

Cited by 3 publications

(3 citation statements)

References 2 publications

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“…Although the toxicity of arsenicals is limited due to their fast elimination and the lack of accumulation in deep organs [2][3], over the years they have fallen out of favour as therapeutic agents. Today there is a renewed interest by researchers in studying arsenicals as drugs for the future, particularly because these drugs are fairly cheap and are therefore suitable as therapeutics for developing countries.…”

Section: Introductionmentioning

confidence: 99%

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Anti-Proliferative Effects of Novel Glyco-Lipid-Arsenicals (III) on MCF-7 Human Breast Cancer Cells

Wimmer¹,

Robinson²,

Gopisetty-Venkata³

et al. 2006

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Arsenic trioxide appears to be effective in the treatment of pro-myelocytic leukaemia. The substituted phenylarsen(III)oxides are highly polar, they have a high tendency to undergo oxidation to As (V) and to form oligomers, to prevent this we protected the As-(OH)(2) group as cyclic dithiaarsanes. To increase the compound's biological stability and passive diffusion we conjugated the compound of interest with lipoamino acids (Laas). Alternatively, we further conjugated the dithiaarsane derivative with a carbohydrate to utilize active transport systems and to target compound. We investigated two novel glyco-lipid arsenicals (III) (compounds 9 and 11) for their ability to initiate MCF-7 breast cancer cell death and characterized the mechanism by which death was initiated. A significant decrease in MCF-7 cell proliferation was observed using 1 microM and 10 microM compound (11) and 10 microM of compound (9). Treatment with compound (11) triggered apoptosis of MFC-7 cells while compound (9) induced inhibition of cellular proliferation was not via rapid induction of apoptosis and more likely reflected necrosis and/or alterations in the cell cycle. Differences in the anti-proliferative potency of the two compounds indicate that structural modifications influence effectiveness.

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Section: Introductionmentioning

confidence: 99%

“…20 (m, 20 H, 10 CH 2 ), 0.86 (t, 3, CH3 ) 13. C NMR (CDCl 3 ): 169.02, 169.40 (2 C, C=O (A, B)), 139.78, 139.20 (2 C, NH linked quart.…”

mentioning

confidence: 98%

Anti-Proliferative Effects of Novel Glyco-Lipid-Arsenicals (III) on MCF-7 Human Breast Cancer Cells

Wimmer¹,

Robinson²,

Gopisetty-Venkata³

et al. 2006

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“…These results suggest that the in vivo activity observed in the mouse and sheep experimental trypanosomiasis models involved the existence of active metabo-lites. Spiroarsorane I had been investigated for plasma kinetics after oral and intravenous administration and the compound had been detected in plasma (Rekik et al 1989). Nevertheless, no identification of metabolites was performed.…”

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confidence: 99%

The effect of spiroarsoranes on Trypanosoma brucei brucei and T. b. rhodesiense

et al. 1996

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Topical application and intraperitoneal administration of spiroarsoranes were carried out to cure central nervous system (CNS) trypanosomiasis in the chronic Trypanosoma brucei GVR 35 mouse model. Topical application appeared more efficient than intraperitoneal injection. The periods of aparasitaemia after treatment were longer but none of the mice was permanently cured. Combination treatment with eflornithine (DFMO) and the spiroarsoranes failed to show any synergistic effect. In addition, spiroarsorane I was evaluated against the T. b. rhodesiense KETRI 2634 strain, whereby 60-mg/kg treatment produced a noticeable prolongation of the life span of trypanosome-positive animals. These in vivo results suggests that the spiroarsoranes have difficulty in crossing the blood-brain barrier (BBB) and clearing the parasites from the CNS or, alternatively, that these strains are less sensitive to pentavalent arsenicals than the T. b. brucei CMP fast strain, which in the present study was more sensitive to spiroarsoranes whose lipophilicity corresponded to a log-P value ranging from 2.5 to 3.7.

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Four compartment mammillary model applied to the pharmacokinetics of a spiroarsorane administered orally to rabbits

Biasi¹,

Rekik²

1991

Journal of Biomedical Engineering

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Pharmacokinetics of Two Spiroarsoranes Administered Intravenously or Orally to Rabbits

Cited by 3 publications

References 2 publications

Anti-Proliferative Effects of Novel Glyco-Lipid-Arsenicals (III) on MCF-7 Human Breast Cancer Cells

Anti-Proliferative Effects of Novel Glyco-Lipid-Arsenicals (III) on MCF-7 Human Breast Cancer Cells

The effect of spiroarsoranes on Trypanosoma brucei brucei and T. b. rhodesiense

Four compartment mammillary model applied to the pharmacokinetics of a spiroarsorane administered orally to rabbits

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