Gold(III) Complexes with 2-(1-Ethylbenzyl)pyridine as Promising Antimicrobial and Antitumor Agents

Antimicrobial resistance (AMR) is one of the most urgent public health problems worldwide; multidrug resistance (MDR) is also of concern. In an effort to find new classes of antibiotics, recent studies have found that coordination compounds of noble metals show promising biological effects both in v...

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Main Authors: Antonio Zucca, Bruna Canu, Maria I. Pilo, Sergio Stoccoro, Giacomo Senzacqua, Sara Fais, Giuseppina Pichiri, Alessandra Scano
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/7/1611
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author Antonio Zucca
Bruna Canu
Maria I. Pilo
Sergio Stoccoro
Giacomo Senzacqua
Sara Fais
Giuseppina Pichiri
Alessandra Scano
author_facet Antonio Zucca
Bruna Canu
Maria I. Pilo
Sergio Stoccoro
Giacomo Senzacqua
Sara Fais
Giuseppina Pichiri
Alessandra Scano
author_sort Antonio Zucca
collection DOAJ
description Antimicrobial resistance (AMR) is one of the most urgent public health problems worldwide; multidrug resistance (MDR) is also of concern. In an effort to find new classes of antibiotics, recent studies have found that coordination compounds of noble metals show promising biological effects both in vitro and in vivo, deserving attention as a new class of possible antimicrobial agents. Metal ions in biological systems can essentially have two roles: structural or functional. In the former, the metal ion serves to stabilize structures, especially proteins, while in the latter, the metal is involved in bio-site reactivity (essentially in metallo-enzymes). Two new complexes with 2-(1-ethyl-benzyl)pyridine (py<sup>eb</sup>), one monodentate adduct and one cyclometalated ([Au(py<sup>eb</sup>)Cl<sub>3</sub>] and [Au(py<sup>eb</sup>-H)Cl<sub>2</sub>], respectively), have been synthesized, characterized, and tested against Gram-positive and Gram-negative bacteria, as well as yeasts, revealing promising antibacterial and antibiofilm properties. The two complexes have been thoroughly characterized by means of 1D and 2D NMR spectroscopy, as well as by cyclic voltammetry, conductivity measurements, FT-IR, and elemental analysis. The study showed that the two derivatives are structurally and chemically different, with the cyclometalated complex being chemically and electrochemically more stable. Antimicrobial assays demonstrated that solutions of the monodentate adduct and of the cyclometalated complex have inhibitory and antibiofilm effects against the pathogenic bacteria <i>E</i>. <i>coli</i>, <i>K</i>. <i>pneumoniae</i>, <i>S</i>. <i>aureus</i>, and <i>S</i>. <i>pyogenes</i> but were unable to reveal a fungicidal effect on <i>C</i>. <i>albicans</i>. A preliminary study was conducted to assess the anti-cancer activity of the compounds, and treatments with the gold compounds also resulted in a significant reduction in the metabolic activity of HT29 colon cancer cells.
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spelling doaj-art-38e6b5b4c61a40e8ab271b32f94db0322025-08-20T02:09:17ZengMDPI AGMolecules1420-30492025-04-01307161110.3390/molecules30071611Gold(III) Complexes with 2-(1-Ethylbenzyl)pyridine as Promising Antimicrobial and Antitumor AgentsAntonio Zucca0Bruna Canu1Maria I. Pilo2Sergio Stoccoro3Giacomo Senzacqua4Sara Fais5Giuseppina Pichiri6Alessandra Scano7Department of Chemical, Physical, Mathematical and Natural Sciences, University of Sassari, Via Vienna 2, 07100 Sassari, ItalyDepartment of Chemical, Physical, Mathematical and Natural Sciences, University of Sassari, Via Vienna 2, 07100 Sassari, ItalyDepartment of Chemical, Physical, Mathematical and Natural Sciences, University of Sassari, Via Vienna 2, 07100 Sassari, ItalyDepartment of Chemical, Physical, Mathematical and Natural Sciences, University of Sassari, Via Vienna 2, 07100 Sassari, ItalyDepartment of Chemical, Physical, Mathematical and Natural Sciences, University of Sassari, Via Vienna 2, 07100 Sassari, ItalyDepartment of Surgical Sciences, University of Cagliari, 09124 Cagliari, ItalyDepartment of Medical Sciences and Public Health, University of Cagliari, 09124 Cagliari, ItalyDepartment of Surgical Sciences, University of Cagliari, 09124 Cagliari, ItalyAntimicrobial resistance (AMR) is one of the most urgent public health problems worldwide; multidrug resistance (MDR) is also of concern. In an effort to find new classes of antibiotics, recent studies have found that coordination compounds of noble metals show promising biological effects both in vitro and in vivo, deserving attention as a new class of possible antimicrobial agents. Metal ions in biological systems can essentially have two roles: structural or functional. In the former, the metal ion serves to stabilize structures, especially proteins, while in the latter, the metal is involved in bio-site reactivity (essentially in metallo-enzymes). Two new complexes with 2-(1-ethyl-benzyl)pyridine (py<sup>eb</sup>), one monodentate adduct and one cyclometalated ([Au(py<sup>eb</sup>)Cl<sub>3</sub>] and [Au(py<sup>eb</sup>-H)Cl<sub>2</sub>], respectively), have been synthesized, characterized, and tested against Gram-positive and Gram-negative bacteria, as well as yeasts, revealing promising antibacterial and antibiofilm properties. The two complexes have been thoroughly characterized by means of 1D and 2D NMR spectroscopy, as well as by cyclic voltammetry, conductivity measurements, FT-IR, and elemental analysis. The study showed that the two derivatives are structurally and chemically different, with the cyclometalated complex being chemically and electrochemically more stable. Antimicrobial assays demonstrated that solutions of the monodentate adduct and of the cyclometalated complex have inhibitory and antibiofilm effects against the pathogenic bacteria <i>E</i>. <i>coli</i>, <i>K</i>. <i>pneumoniae</i>, <i>S</i>. <i>aureus</i>, and <i>S</i>. <i>pyogenes</i> but were unable to reveal a fungicidal effect on <i>C</i>. <i>albicans</i>. A preliminary study was conducted to assess the anti-cancer activity of the compounds, and treatments with the gold compounds also resulted in a significant reduction in the metabolic activity of HT29 colon cancer cells.https://www.mdpi.com/1420-3049/30/7/1611Gold(III) cyclometalated compoundsnitrogen ligandsantimicrobial complexeslaboratory medicine
spellingShingle Antonio Zucca
Bruna Canu
Maria I. Pilo
Sergio Stoccoro
Giacomo Senzacqua
Sara Fais
Giuseppina Pichiri
Alessandra Scano
Gold(III) Complexes with 2-(1-Ethylbenzyl)pyridine as Promising Antimicrobial and Antitumor Agents
Molecules
Gold(III) cyclometalated compounds
nitrogen ligands
antimicrobial complexes
laboratory medicine
title Gold(III) Complexes with 2-(1-Ethylbenzyl)pyridine as Promising Antimicrobial and Antitumor Agents
title_full Gold(III) Complexes with 2-(1-Ethylbenzyl)pyridine as Promising Antimicrobial and Antitumor Agents
title_fullStr Gold(III) Complexes with 2-(1-Ethylbenzyl)pyridine as Promising Antimicrobial and Antitumor Agents
title_full_unstemmed Gold(III) Complexes with 2-(1-Ethylbenzyl)pyridine as Promising Antimicrobial and Antitumor Agents
title_short Gold(III) Complexes with 2-(1-Ethylbenzyl)pyridine as Promising Antimicrobial and Antitumor Agents
title_sort gold iii complexes with 2 1 ethylbenzyl pyridine as promising antimicrobial and antitumor agents
topic Gold(III) cyclometalated compounds
nitrogen ligands
antimicrobial complexes
laboratory medicine
url https://www.mdpi.com/1420-3049/30/7/1611
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