title: Highly cytotoxic bioconjugated gold(I) complexes with cysteine-containing dipeptides.
abstract: 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 Boc2 O 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.
authors.affiliation: Departamento de Química Inorgánica, Instituto Síntesis Química y Catálisis Homogénea (ISQCH), CSIC-Universidad de Zaragoza, Pedro Cerbuna 12, 50009 Zaragoza (Spain).
authors.forename: Alejandro
authors.initials: A
authors.lastname: Gutiérrez
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Universidad de Zaragoza, Pedro Cerbuna 12, 50009 Zaragoza (Spain).
authors.forename: Isabel
authors.initials: I
authors.lastname: Marzo
authors.affiliation: Departamento de Química Orgánica, Instituto Síntesis Química y Catálisis Homogénea (ISQCH), CSIC-Universidad de Zaragoza, Pedro Cerbuna 12, 50009 Zaragoza (Spain).
authors.forename: Carlos
authors.initials: C
authors.lastname: Cativiela
authors.affiliation: Departamento de Química Inorgánica, Instituto Síntesis Química y Catálisis Homogénea (ISQCH), CSIC-Universidad de Zaragoza, Pedro Cerbuna 12, 50009 Zaragoza (Spain).
authors.forename: Antonio
authors.initials: A
authors.lastname: Laguna
authors.affiliation: Departamento de Química Inorgánica, Instituto Síntesis Química y Catálisis Homogénea (ISQCH), CSIC-Universidad de Zaragoza, Pedro Cerbuna 12, 50009 Zaragoza (Spain). gimeno@unizar.es.
authors.forename: M Concepción
authors.initials: MC
authors.lastname: Gimeno
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D003545:Cysteine / Q000737:chemistry / Q000494:pharmacology*; D004151:Dipeptides / Q000737:chemistry / Q000494:pharmacology*; D006046:Gold / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D010720:Phosphines / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D004151:Dipeptides; D010720:Phosphines; D006046:Gold; C044646:phosphine; D003545:Cysteine
keywords: bioconjugation; cytotoxic activity; dipeptides; gold; medicinal chemistry