Gold(III) heteroleptic complexes with SNS-thiosemicarbazonate ligands as cytotoxic agents: Experimental and computational insights into the mechanism of action
Gold(III) heteroleptic complexes have been evaluated in cytotoxic assays involving B16-F10, HCT-8, MDA-MB-231 tumor cell lines and VERO cells. Experimental and theoretical studies suggest that, while DNA is not indicated as a target of these compounds, HSA and thioredoxin reductase can act as their...
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Published in | Polyhedron Vol. 219; pp. 115767 - 115777 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
OXFORD
Elsevier Ltd
01.06.2022
Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | Gold(III) heteroleptic complexes have been evaluated in cytotoxic assays involving B16-F10, HCT-8, MDA-MB-231 tumor cell lines and VERO cells. Experimental and theoretical studies suggest that, while DNA is not indicated as a target of these compounds, HSA and thioredoxin reductase can act as their potential carrier and target, respectively.
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•New AuIII heteroleptic complexes were prepared from a tridentate thiosemicarbazone.•The cytotoxicity on B16-F10, HCT-8, MDA-MB-231 and VERO cell lines was assessed.•The complexes display remarkable cytotoxic effects for the MDA-MB-231 cell line.•Their interaction with DNA, HSA and thioredoxin reductase was also evaluated.•Thioredoxin reductase was found to be a potential target of the AuIII complexes.
New gold(III) heteroleptic complexes of general formula [AuX(dmtsc)], with (dmtsc)2– = (diethylaminothiocarbonyl)benzimidoyl-morpholinyl-thiosemicarbazonate and X = xant– (ethyl xanthate) or damp– (dimethyl-1-phenylmethanamine), were synthesized and compared to the chlorido precursor [AuCl(dmtsc)]. The characterization of the new complexes included FTIR, elemental analysis, molar conductivity, UV–Vis, 1H and 13C NMR spectroscopies and ESI(+)-MS. In addition, the xanthate derivative was analyzed by single-crystal X-ray diffraction. In vitro assays against three tumor cell lines (B16-F10, HCT-8 and MDA-MB-231) showed that the gold(III) complexes display remarkable antiproliferative effects on human breast adenocarcinoma cell line with influence of the co-ligands. The cytotoxicity on VERO cells was also investigated revealing that the organometallic complex [Au(damp)(dmtsc)] was the most selective compound for MDA-MB-231, although not the most active. Attempting to comprehend their behavior in biological medium, studies involving the interactions with possible biological targets were performed by experimental methods and theoretical docking simulations. Their results indicated that HSA might be a probable carrier of the compounds in the biological medium, whereas DNA is not supposed to be their main target. On the other hand, all compounds totally inhibited thioredoxin reductase enzyme (TrxR) at the concentration of 50 μM and formed significant molecular interactions, suggesting that it might be one of the molecular targets of these gold(III) complexes. |
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ISSN: | 0277-5387 1873-3719 |
DOI: | 10.1016/j.poly.2022.115767 |