Synthesis of New Gold(I) Thiolates Containing Amino Acid Moieties with Potential Biological Interest

Gutiérrez, Alejandro García; Bernal, Javier García; Villacampa, M. Dolores; Cativiela, Carlos; Laguna, Antonio; Gimeno, M. Concepción

doi:10.1021/ic4003803

Cited by 20 publications

(17 citation statements)

References 35 publications

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“…In our aim of preparing gold complexes with cysteine‐containing dipeptides we thought of using as precursor the previously described complex, Ac‐Cys(AuPPh 3 )‐OH, in which there is an acid moiety that could couple with other amino acid esters, in a similar manner as we have reported earlier for the gold‐phosphine complexes with the nicotinic acid thiolate 18a. However, the preparation of the desired complexes was not possible by this route, probably because of solubility reasons.…”

Section: Resultsmentioning

confidence: 99%

Highly Cytotoxic Bioconjugated Gold(I) Complexes with Cysteine‐Containing Dipeptides

Gutiérrez

Marzo

Cativiela

et al. 2015

Chemistry A European J

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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.

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Section: Resultsmentioning

confidence: 99%

Highly Cytotoxic Bioconjugated Gold(I) Complexes with Cysteine‐Containing Dipeptides

Gutiérrez

Marzo

Cativiela

et al. 2015

Chemistry A European J

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“…In addition, a number of gold conjugates derived from amino acids or peptides have been reported. As examples, N‐heterocyclic carbene (NHC)–gold complexes,, conjugates of ferrocene coordinated to gold(I) derivatives, gold(III) dithiocarbamates,, gold(I) azides, and gold(I) thiolates, with only one example of a chloro–gold–phosphane found in the recent literature.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Gold(I) Derivatives Bearing Alkylated 1,3,5‐Triaza‐7‐phosphaadamantane as Selective Anticancer Metallodrugs

et al. 2016

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The alkylation of one of the nitrogen atoms of the molecule 1,3,5,triaza‐7‐phosphaadamantane (PTA) with para‐substituted benzylic units and the l‐phenylalanine methyl ester moiety are reported. The crystalline structures of the two alkylated PTA species [PTA‐CH2‐p‐COOH‐C6H4]Br (1a) and [PTA‐CH2‐p‐CH2COOH‐C6H4]Br (2) reveal the presence of interactions between the bromide anion and the OH group of the acid moiety. Bis‐phosphane derivatives were prepared by the alkylation of two PTA molecules with a dibromide salt to afford more water‐soluble species. The corresponding mono‐ and dinuclear chloro‐, thiocyanato‐ and pentafluorophenyl gold(I) derivatives are described. Most of the new complexes have been tested as anticancer agents, exhibiting higher cytotoxicity than cisplatin against human colon cancer cell lines. Some of them display low cytotoxicity towards differentiated cells (non‐carcinogenic), as determined from viability studies, thereby demonstrating a significant specificity in this type of cancer.

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“…The antiproliferative activity against different tumor cell lines was shown by gold(I) complexes obtained from the reaction of [Au(SPyCOOH)(PR3)] complex (SPyCOOH = nicotinic acid thiolate) by the functionalization of its carboxylic group with different amino acids, ester or amide derivatives of these amino acids or with peptide moieties [20,21]. Gold(I) complexes 7-24 of the general formula [Au(SPyCOR)(PPh3)], in which R = methyl ester of amino acid (7)(8)(9)(10)(11)(12), amino acid (13)(14)(15)(16)(17)(18) and amide derivative of the corresponding amino acid (19)(20)(21)(22)(23)(24) have been structurally modified.…”

Section: Gold(i) Complexes Containing Amino Acids and Peptides Moietiesmentioning

confidence: 99%

Amino Acids and Peptides as Versatile Ligands in the Synthesis of Antiproliferative Gold Complexes

2020

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Gold complexes have been traditionally employed in medicine, and currently, some gold(I) complexes, such as auranofin, are clinically used in the treatment of rheumatoid arthritis. In the last decades, both gold(I) and gold(III) complexes with different types of ligands have gained considerable attention as potential antitumor agents, showing superior activity both in vitro and in vivo to some of the clinically used agents. The present review article summarizes the results achieved in the field of synthesis and evaluation of gold complexes with amino acids and peptides moieties for their cytotoxicity. The first section provides an overview of the gold(I) complexes with amino acids and peptides, which have shown antiproliferative activity, while the second part is focused on the activity of gold(III) complexes with these ligands. A systematic summary of the results achieved in the field of gold(I/III) complexes with amino acids and peptides could contribute to the future development of metal complexes with these biocompatible ligands as promising antitumor agents.

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Synthesis of New Gold(I) Thiolates Containing Amino Acid Moieties with Potential Biological Interest

Cited by 20 publications

References 35 publications

Highly Cytotoxic Bioconjugated Gold(I) Complexes with Cysteine‐Containing Dipeptides

Highly Cytotoxic Bioconjugated Gold(I) Complexes with Cysteine‐Containing Dipeptides

Synthesis of Gold(I) Derivatives Bearing Alkylated 1,3,5‐Triaza‐7‐phosphaadamantane as Selective Anticancer Metallodrugs

Amino Acids and Peptides as Versatile Ligands in the Synthesis of Antiproliferative Gold Complexes

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