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Highly Cytotoxic Bioconjugated Gold(I) Complexes with Cysteine‐Containing Dipeptides
Author(s) -
Gutiérrez Alejandro,
Marzo Isabel,
Cativiela Carlos,
Laguna Antonio,
Gimeno M. Concepción
Publication year - 2015
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201501458
Subject(s) - dipeptide , chemistry , cysteine , amino acid , stereochemistry , cystine , phosphine , auranofin , combinatorial chemistry , thiol , organic chemistry , biochemistry , enzyme , catalysis , biology , rheumatoid arthritis , immunology
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 Boc 2 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(PPh 3 )] gives the gold‐dipeptide‐phosphine species. Starting from these formally gold(I) thiolate–dipeptide phosphine complexes with the general formula [Au(SR)(PR 3 )] 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 IC 50 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.