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

Abstract

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.

Selective Anticancer and Antimicrobial Metallodrugs Based on Gold(III) Dithiocarbamate Complexes

“…C1 – 4 complexes were also shown to be effective against E. coli , a bacteria that can induce infections of the gastrointestinal and urinary tracts. Although the MIC values of 32 µg/mL obtained against the E. coli strain were significantly higher than those obtained against Sa, they can still be considered great results since other similar gold(III) complexes did not inhibit the growth of the E. coli strain (≤125 mg/mL) or other Gram-negative bacteria such as K. pneumonia , p. aeruginosa , or Acinetobacter baumannii [ 89 , 90 ]. Although S. aureus was the only Gram-positive bacteria tested, it seemed that our complexes were more effective against Gram-positive than Gram-negative bacteria.…”

Studying Peptide-Metal Ion Complex Structures by Solution-State NMR

“…Novel therapeutics can be formed using metallopeptides: Certain antimicrobial peptides naturally feature an amino terminal copper and nickel-binding (ATCUN) motif [49,50], and the specificity, solubility and stability of other antimicrobial peptides have been improved through metal-binding to increase microbial resistance [51,52]. Peptides with antitumor activity include, e.g., cytotoxic gold-peptide complexes [53] and bicyclic peptides developed to bind metal for potential radiopharmaceuticals [54]. Peptides that feature metal-binding sites can function as biocatalysts [55] and can also be used to direct chiral synthesis [56].…”

Emerging Molecular Receptors for the Specific-Target Delivery of Ruthenium and Gold Complexes into Cancer Cells

“…Although not reviewed in detail in this manuscript, biomolecules, such as amino acids, vitamins, and carbohydrates, are among the most common and broadly studied delivering agents of anticancer drugs into tumors [ 11 ]. There are numerous reports of bioconjugates containing ruthenium and gold complexes for targeted anticancer applications that have been reported and discussed elsewhere [ 98 , 99 , 100 , 101 , 102 ]. Herein, we selected a couple of examples for illustrative purposes (see Section 5.2 ).…”

“…An extensive number of inorganic and organometallic gold and ruthenium complexes have been conjugated to several different biomolecules for targeted anticancer purposes. These include systems targeting the amino acid transporters [ 102 , 106 , 107 , 108 , 109 ], peptide transporters [ 110 , 111 ], glucose transporters [ 69 , 112 , 113 ], and vitamin transporters [ 77 , 114 , 115 , 116 , 117 , 118 ]. As our review mainly focuses on the emerging receptors for the target delivery of ruthenium and gold complexes into cancer cells, for which the use of biomolecules as delivering carriers is well-known and is out of our scope, we will not discuss them in further detail.…”