Synthesis, Characterization, and Cytotoxic Activity of AuI N, S‐Heterocyclic Carbenes Derived from Peptides Containing L‐Thiazolylalanine. Issue 15 (22nd April 2014)

• Record Type: Journal Article
• Authors: Gutiérrez, Alejandro; Gimeno, M. Concepción; Marzo, Isabel; Metzler‐Nolte, Nils
• Is Part Of: European journal of inorganic chemistry. Issue 15(2014)
• Page Start: 2512
• Page End: 2519
• Publication Date: 2014-04-22
• Subjects: Antitumor agents -- Carbenes -- Drug design -- Gold -- Medicinal chemistry -- Metal‐based drugs -- Peptides; Chemistry, Inorganic -- Periodicals; Organometallic chemistry -- Periodicals; Bioinorganic chemistry -- Periodicals; Solid state chemistry -- Periodicals; 546
• DOI: 10.1002/ejic.201402103
• Languages: English
• ISSNs: 1434-1948

Abstract

Abstract: Thiazolium salts2a –b derived from a dipeptide Boc‐Gly‐(Thz‐Ala)‐OMe (1b ) containing the nonproteinogenic amino acidL ‐thiazolylalanine (Thz‐Ala) can be used to generate the corresponding N, S‐heterocyclic carbene (NSHC) gold(I) (3a –b ) and silver(I) (4 ) complexes. Reaction of the NSHC‐gold(I) iodide3b with Boc‐Cys‐Gly‐OMe gives access to the peptide bioconjugate5, which contains a NSHC‐Au‐(S‐Cys) unit. Compounds3 –5 constitute the first coin metal NSHC‐peptide complexes. All new compounds were comprehensively characterized by 1 H, 13 C and 2D‐NMR spectroscopy, IR spectroscopy, and mass spectrometry. Their cytotoxicity was studied in vitro against three different tumor cell lines (A549, Jurkat T and MiaPaca2) and IC50 values in the low micromolar range (< 25 μM ), and as low as 0.4 μM in the best case were observed. All new Au complexes show good stability and promising properties and, as a result, this novel type of gold(I) carbene complex opens possibilities for the design of new metal‐based drugs with promising antitumor characteristics. Abstract : The first organometallic gold(I) bioconjugates of a thiazole‐based peptide are reported. The N, S‐heterocyclic carbene gold(I) derivatives were prepared from the corresponding thiazolium peptide salts either by following the Ag2 O route or by reaction with a strong base. The new compounds display excellent in vitro cytotoxicity with IC50 values as low as 0.4 μM .