Gold(I) thiolates containing amino acid moieties. Cytotoxicity and structure-activity relationship studies
| Autor: | Isabel Marzo, Carlos Cativiela, Alejandro Gutiérrez, Lucia Gracia-Fleta, Antonio Laguna, M. Concepción Gimeno |
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| Přispěvatelé: | Ministerio de Economía y Competitividad (España), European Commission, Diputación General de Aragón, Consejo Superior de Investigaciones Científicas (España), Fundación Científica Asociación Española Contra el Cáncer |
| Rok vydání: | 2014 |
| Předmět: |
chemistry.chemical_classification
Dipeptide Ligand Stereochemistry Phosphines Peptide Apoptosis Amino acid Cell Line Inorganic Chemistry chemistry.chemical_compound Jurkat Cells Structure-Activity Relationship chemistry Coordination Complexes Structure–activity relationship Humans Transition metal thiolate complex Gold Sulfhydryl Compounds Amino Acids Cytotoxicity Reactive Oxygen Species Phosphine Cell Proliferation |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | Several gold(i) complexes containing a thiolate ligand functionalised with several amino acid or peptide moieties of the type [Au(SPyCOR)(PPh2R′)] (where R = OH, amino acid or dipeptide and R′ = Ph or Py) were prepared. These thiolate gold complexes bearing biological molecules possess potential use as antitumor agents. Cytotoxicity assays in different tumour cell lines such as A549 (lung carcinoma), Jurkat (T-cell leukaemia) and MiaPaca2 (pancreatic carcinoma) revealed that the complexes exhibit good antiproliferative activity, with IC50 values in the low micromolar range. Several structural modifications such as in the type of phosphine, number of metal atoms and amino acid (type, stereochemistry and functionalisation) were carried out in order to establish the structure-activity relationship in this family of complexes, which has led to the design of new and more potent cytotoxic complexes. Observations of different cellular events after addition of the complexes indicated the possible mechanism of action or the biological targets of this type of new gold(i) drug. The authors thank the Ministerio de Economía y Competitividad (MEC/FEDER CTQ2013-48635-C2-1-P, CTQ2010-17436 and SAF2010-14920) and DGA-FSE (E77, E40 and B16) for financial support. A.G. thanks the CSIC for a JAE-predoc fellowship. LGF was the recipient of an AECC fellowship. |
| Databáze: | OpenAIRE |
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