Bifunctional antitumor compounds: synthesis and characterization of a Au(III)-streptonigrin complex with thiol-modulating properties.
In order to synthesize bifunctional antitumor compounds, the interaction of streptonigrin with [AuCl4]- has been studied. Using absorption, circular dichroism, and fluorescence measurements, we have shown that streptonigrin forms with Au(III) a 1:1 Au(III)-streptonigrin complex. This complex is very stable as long as gold is in the trivalent state and is able to inhibit glutathione reductase activity. In the presence of biological agents such as NADH and reduced glutathione, Au(III) is slowly reduced to Au(I) and removed from its binding site to streptonigrin. Original streptonigrin is thus recovered. This complex exhibits antitumor activity against P-388 leukemia which compares with that of the free drug.
Moustatih
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Laboratoire de Chimie Bioinorganique (UA CNRS 198), UFR de Santé, Médecine et Biologie Humaine, Université Paris Nord, Bobigny, France.
Garnier-Suillerot
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D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis; D055598:Chemical Phenomena; D002621:Chemistry; D002942:Circular Dichroism; D003432:Cross-Linking Reagents / Q000138:chemical synthesis; D004563:Electrochemistry; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006046:Gold; D051379:Mice; D009243:NAD / Q000378:metabolism; D009245:NADH Dehydrogenase / Q000378:metabolism; D010084:Oxidation-Reduction; D013057:Spectrum Analysis; D013308:Streptonigrin / Q000494:pharmacology; D013438:Sulfhydryl Compounds; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D013438:Sulfhydryl Compounds; D009243:NAD; D013308:Streptonigrin; D006046:Gold; D009245:NADH Dehydrogenase; D005980:Glutathione Reductase