Antimicrobial Activity of Copper(II), Nickel(II) and Zinc(II) Complexes with Semicarbazone and Thiosemicarbazone Ligands Derived from Substituted Salicylaldehydes

Antibiotic resistance is a problem repeatedly reported by health authorities. Metalloantibiotics, i.e., biologically active compounds containing one or more metal ions, can be an important resource in the fight against bacteria and fungi. Here, we report the results obtained with a panel of copper(I...

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Main Authors: Alessio Zavaroni, Luca Rigamonti, Franco Bisceglie, Mauro Carcelli, Giorgio Pelosi, Giovanna Angela Gentilomi, Dominga Rogolino, Francesca Bonvicini
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Language:English
Published: MDPI AG 2025-05-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/11/2329
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author Alessio Zavaroni
Luca Rigamonti
Franco Bisceglie
Mauro Carcelli
Giorgio Pelosi
Giovanna Angela Gentilomi
Dominga Rogolino
Francesca Bonvicini
author_facet Alessio Zavaroni
Luca Rigamonti
Franco Bisceglie
Mauro Carcelli
Giorgio Pelosi
Giovanna Angela Gentilomi
Dominga Rogolino
Francesca Bonvicini
author_sort Alessio Zavaroni
collection DOAJ
description Antibiotic resistance is a problem repeatedly reported by health authorities. Metalloantibiotics, i.e., biologically active compounds containing one or more metal ions, can be an important resource in the fight against bacteria and fungi. Here, we report the results obtained with a panel of copper(II), nickel(II) and zinc(II) complexes with thiosemicarbazone, semicarbazone and acylhydrazone ligands on <i>Staphylococcus aureus</i>, <i>Escherichia coli</i> and <i>Candida albicans</i>, taken as model systems of human pathogens. To increase the solubility in water, the sulfonic group was introduced on some of the ligands, isolating them as sodium salts (NaH<sub>2</sub>L4-NaH<sub>2</sub>L7). Complexes <b>1</b>–<b>14</b> were isolated, fully characterized and the X-ray structures of <b>11</b>, <b>12</b> and <b>13</b> were obtained. While all the ligands have no antimicrobial activity, the copper(II) complexes <b>1</b> and <b>4</b> and the nickel(II) complex <b>2</b>, obtained from thiosemicarbazone ligands, showed good activity, in particular against <i>S. aureus</i>; these complexes were investigated in depth, calculating their respective IC<sub>50</sub> values (4.2 μM, 3.5 μM and 61.8 μM, respectively). It should be noted that nickel(II) complex <b>2</b> does not show hemolytic activity and has a favorable SI value. While all the copper(II) complexes completely degraded the plasmid DNA in presence of H<sub>2</sub>O<sub>2</sub>, nickel(II) complex <b>2</b> cleaved the plasmid DNA leading to the formation of the relaxed nicked conformation, thus suggesting a different mechanism of action.
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spelling doaj-art-ccb827e7a95a43a0b3327680e700e7d42025-08-20T02:33:02ZengMDPI AGMolecules1420-30492025-05-013011232910.3390/molecules30112329Antimicrobial Activity of Copper(II), Nickel(II) and Zinc(II) Complexes with Semicarbazone and Thiosemicarbazone Ligands Derived from Substituted SalicylaldehydesAlessio Zavaroni0Luca Rigamonti1Franco Bisceglie2Mauro Carcelli3Giorgio Pelosi4Giovanna Angela Gentilomi5Dominga Rogolino6Francesca Bonvicini7Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area delle Scienze 17/A, 43124 Parma, ItalyDipartimento di Scienze Chimiche e Geologiche, Università degli Studi di Modena e Reggio Emilia, Via G. Campi 103, 41125 Modena, ItalyDepartment of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area delle Scienze 17/A, 43124 Parma, ItalyDepartment of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area delle Scienze 17/A, 43124 Parma, ItalyDepartment of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area delle Scienze 17/A, 43124 Parma, ItalyDepartment of Pharmacy and Biotechnology, University of Bologna, Via Massarenti 9, 40138 Bologna, ItalyDepartment of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area delle Scienze 17/A, 43124 Parma, ItalyDepartment of Pharmacy and Biotechnology, University of Bologna, Via Massarenti 9, 40138 Bologna, ItalyAntibiotic resistance is a problem repeatedly reported by health authorities. Metalloantibiotics, i.e., biologically active compounds containing one or more metal ions, can be an important resource in the fight against bacteria and fungi. Here, we report the results obtained with a panel of copper(II), nickel(II) and zinc(II) complexes with thiosemicarbazone, semicarbazone and acylhydrazone ligands on <i>Staphylococcus aureus</i>, <i>Escherichia coli</i> and <i>Candida albicans</i>, taken as model systems of human pathogens. To increase the solubility in water, the sulfonic group was introduced on some of the ligands, isolating them as sodium salts (NaH<sub>2</sub>L4-NaH<sub>2</sub>L7). Complexes <b>1</b>–<b>14</b> were isolated, fully characterized and the X-ray structures of <b>11</b>, <b>12</b> and <b>13</b> were obtained. While all the ligands have no antimicrobial activity, the copper(II) complexes <b>1</b> and <b>4</b> and the nickel(II) complex <b>2</b>, obtained from thiosemicarbazone ligands, showed good activity, in particular against <i>S. aureus</i>; these complexes were investigated in depth, calculating their respective IC<sub>50</sub> values (4.2 μM, 3.5 μM and 61.8 μM, respectively). It should be noted that nickel(II) complex <b>2</b> does not show hemolytic activity and has a favorable SI value. While all the copper(II) complexes completely degraded the plasmid DNA in presence of H<sub>2</sub>O<sub>2</sub>, nickel(II) complex <b>2</b> cleaved the plasmid DNA leading to the formation of the relaxed nicked conformation, thus suggesting a different mechanism of action.https://www.mdpi.com/1420-3049/30/11/2329metalloantibioticsacylhydrazonethiosemicarbazoneantimicrobial activitycytotoxicityhemolytic properties
spellingShingle Alessio Zavaroni
Luca Rigamonti
Franco Bisceglie
Mauro Carcelli
Giorgio Pelosi
Giovanna Angela Gentilomi
Dominga Rogolino
Francesca Bonvicini
Antimicrobial Activity of Copper(II), Nickel(II) and Zinc(II) Complexes with Semicarbazone and Thiosemicarbazone Ligands Derived from Substituted Salicylaldehydes
Molecules
metalloantibiotics
acylhydrazone
thiosemicarbazone
antimicrobial activity
cytotoxicity
hemolytic properties
title Antimicrobial Activity of Copper(II), Nickel(II) and Zinc(II) Complexes with Semicarbazone and Thiosemicarbazone Ligands Derived from Substituted Salicylaldehydes
title_full Antimicrobial Activity of Copper(II), Nickel(II) and Zinc(II) Complexes with Semicarbazone and Thiosemicarbazone Ligands Derived from Substituted Salicylaldehydes
title_fullStr Antimicrobial Activity of Copper(II), Nickel(II) and Zinc(II) Complexes with Semicarbazone and Thiosemicarbazone Ligands Derived from Substituted Salicylaldehydes
title_full_unstemmed Antimicrobial Activity of Copper(II), Nickel(II) and Zinc(II) Complexes with Semicarbazone and Thiosemicarbazone Ligands Derived from Substituted Salicylaldehydes
title_short Antimicrobial Activity of Copper(II), Nickel(II) and Zinc(II) Complexes with Semicarbazone and Thiosemicarbazone Ligands Derived from Substituted Salicylaldehydes
title_sort antimicrobial activity of copper ii nickel ii and zinc ii complexes with semicarbazone and thiosemicarbazone ligands derived from substituted salicylaldehydes
topic metalloantibiotics
acylhydrazone
thiosemicarbazone
antimicrobial activity
cytotoxicity
hemolytic properties
url https://www.mdpi.com/1420-3049/30/11/2329
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