Highly cytotoxic bioconjugated gold(I) complexes with cysteine-containing dipeptides
Several gold(I) complexes with cysteine-containing dipeptides have been prepared starting from cystine by coupling different amino acids and using several orthogonal protections. The first step is the reaction of cystine, where the sulfur centre is protected as disulfide, with Boc2O in order to prot...
| Autores: | , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2015 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/123038 |
| Acceso en línea: | http://hdl.handle.net/10261/123038 |
| Access Level: | acceso abierto |
| Palabra clave: | Bioconjugation Cytotoxic activity Dipeptides Gold Medicinal chemistry |
| Sumario: | Several gold(I) complexes with cysteine-containing dipeptides have been prepared starting from cystine by coupling different amino acids and using several orthogonal protections. The first step is the reaction of cystine, where the sulfur centre is protected as disulfide, with Boc2O in order to protect the amino group, followed by coupling of an amino acid ester; finally the disulfide bridge is broken with mercaptoethanol to afford the dipeptide derivative. Further reaction with [AuCl(PPh3)] gives the gold-dipeptide-phosphine species. Starting from these formally gold(I) thiolate–dipeptide phosphine complexes with the general formula [Au(SR)(PR3)] different structural modifications, such as change in the type of the amino protecting group, the type of phosphine, the number of gold(I) atoms per molecule, or the use of a non-proteinogenic conformationally restricted amino acid ester, were introduced in order to evaluate their influence in the biological activity of the final complexes. The cytotoxic activity, in vitro, of these complexes was evaluated against different tumour human cell lines (A549, MiaPaca2 and Jurkat). The complexes show an outstanding cytotoxic activity with IC50 values in the very low micromolar range. Structure–activity relationship studies from the complexes open the possibility of designing more potent and promising gold(I) anticancer agents. |
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