Antiproliferative Properties of a Few Auranofin-Related Gold (I) and Silver (I) Complexes in Leukemia Cells and their Interferences with the Ubiquitin Proteasome System

Abstract

A group of triethylphosphine gold(I) and silver(I) complexes, structurally related to auranofin, were prepared and investigated as potential anticancer drug candidates. The antiproliferative properties of these metal compounds were assessed against two leukemia cell lines, i.e., CCRF-CEM and its multidrug-resistant counterpart, CEM/ADR5000. Interestingly, potent cytotoxic effects were disclosed for both series of compounds against leukemia cells, with IC50 values generally falling in the low-micromolar range, the gold derivatives being on the whole more effective than the silver analogues. Some initial structure-function relationships were drawn. Subsequently, the ability of the study compounds to inhibit the three main catalytic activities of the proteasome was investigated. Different patterns of enzyme inhibition emerged for the various metal complexes. Notably, gold compounds were able to inhibit effectively both the trypsin-like and chymotrypsin-like proteasome activities, being less effective toward the caspase-like catalytic activity. In most cases, a significant selectivity of the study compounds toward the proteasome proteolytic activities was detected when compared to other proteases. The implications of the obtained results are discussed.

Autoren

Damiano Cirri
Tanja Schirmeister
Ean-Jeong Seo
Thomas Efferth
Lara Massai
Luigi Messori
Nicola Micale

DOI

10.3390/molecules25194454

eISSN

1420-3049

Ausgabe der Veröffentlichung

19

Zeitschrift

Molecules

Sprache

en

Online publication date

2020

Paginierung

4454 - 4454

Status

Published online

Herausgeber

MDPI AG

Herausgeber URL

http://dx.doi.org/10.3390/molecules25194454

Datum der Datenerfassung

2020

Titel

Antiproliferative Properties of a Few Auranofin-Related Gold(I) and Silver(I) Complexes in Leukemia Cells and their Interferences with the Ubiquitin Proteasome System

Ausgabe der Zeitschrift

25

Datenquelle: Crossref

Abstract

A group of triethylphosphine gold(I) and silver(I) complexes, structurally related to auranofin, were prepared and investigated as potential anticancer drug candidates. The antiproliferative properties of these metal compounds were assessed against two leukemia cell lines, i.e., CCRF-CEM and its multidrug-resistant counterpart, CEM/ADR5000. Interestingly, potent cytotoxic effects were disclosed for both series of compounds against leukemia cells, with IC<sub>50</sub> values generally falling in the low-micromolar range, the gold derivatives being on the whole more effective than the silver analogues. Some initial structure-function relationships were drawn. Subsequently, the ability of the study compounds to inhibit the three main catalytic activities of the proteasome was investigated. Different patterns of enzyme inhibition emerged for the various metal complexes. Notably, gold compounds were able to inhibit effectively both the trypsin-like and chymotrypsin-like proteasome activities, being less effective toward the caspase-like catalytic activity. In most cases, a significant selectivity of the study compounds toward the proteasome proteolytic activities was detected when compared to other proteases. The implications of the obtained results are discussed.

Addresses

Department of Chemistry and Industrial Chemistry (DCCI), University of Pisa, Via Moruzzi 13, 56124 Pisa, Italy.

Autoren

Damiano Cirri
Tanja Schirmeister
Ean-Jeong Seo
Thomas Efferth
Lara Massai
Luigi Messori
Nicola Micale

DOI

10.3390/molecules25194454

eISSN

1420-3049

Externe Identifier

PubMed Identifier: 32998355
PubMed Central ID: PMC7582876

Open access

true

ISSN

1420-3049

Ausgabe der Veröffentlichung

19

Zeitschrift

Molecules (Basel, Switzerland)

Schlüsselwörter

Cell Line, Tumor
Humans
Leukemia
Gold
Silver
Auranofin
Proteasome Endopeptidase Complex
Ubiquitin
Inhibitory Concentration 50
Drug Resistance, Multiple
Cell Proliferation
Drug Resistance, Neoplasm

Sprache

eng

Medium

Electronic

Online publication date

2020

Open access status

Open Access

Paginierung

E4454

Datum der Veröffentlichung

2020

Status

Published

Publisher licence

CC BY

Datum der Datenerfassung

2020

Titel

Antiproliferative Properties of a Few Auranofin-Related Gold(I) and Silver(I) Complexes in Leukemia Cells and their Interferences with the Ubiquitin Proteasome System.

Sub types

research-article
Journal Article

Ausgabe der Zeitschrift

25

Files

https://www.mdpi.com/1420-3049/25/19/4454/pdf?version=1601294190 https://europepmc.org/articles/PMC7582876?pdf=render

Datenquelle: Europe PubMed Central

Abstract

A group of triethylphosphine gold(I) and silver(I) complexes, structurally related to auranofin, were prepared and investigated as potential anticancer drug candidates. The antiproliferative properties of these metal compounds were assessed against two leukemia cell lines, i.e., CCRF-CEM and its multidrug-resistant counterpart, CEM/ADR5000. Interestingly, potent cytotoxic effects were disclosed for both series of compounds against leukemia cells, with IC50 values generally falling in the low-micromolar range, the gold derivatives being on the whole more effective than the silver analogues. Some initial structure-function relationships were drawn. Subsequently, the ability of the study compounds to inhibit the three main catalytic activities of the proteasome was investigated. Different patterns of enzyme inhibition emerged for the various metal complexes. Notably, gold compounds were able to inhibit effectively both the trypsin-like and chymotrypsin-like proteasome activities, being less effective toward the caspase-like catalytic activity. In most cases, a significant selectivity of the study compounds toward the proteasome proteolytic activities was detected when compared to other proteases. The implications of the obtained results are discussed.

Date of acceptance

2020

Autoren

Damiano Cirri
Tanja Schirmeister
Ean-Jeong Seo
Thomas Efferth
Lara Massai
Luigi Messori
Nicola Micale

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/32998355

DOI

10.3390/molecules25194454

eISSN

1420-3049

Externe Identifier

PubMed Central ID: PMC7582876

Ausgabe der Veröffentlichung

19

Zeitschrift

Molecules

Schlüsselwörter

antiproliferative properties
auranofin
leukemia cells
metal complexes
proteasome inhibition
Auranofin
Cell Line, Tumor
Cell Proliferation
Drug Resistance, Multiple
Drug Resistance, Neoplasm
Gold
Humans
Inhibitory Concentration 50
Leukemia
Proteasome Endopeptidase Complex
Silver
Ubiquitin

Sprache

eng

Country

Switzerland

PII

molecules25194454

Datum der Veröffentlichung

2020

Status

Published online

Datum, an dem der Datensatz öffentlich gemacht wurde

2021

Titel

Antiproliferative Properties of a Few Auranofin-Related Gold(I) and Silver(I) Complexes in Leukemia Cells and their Interferences with the Ubiquitin Proteasome System.

Sub types

Journal Article

Ausgabe der Zeitschrift

25

Datenquelle: PubMed

Autoren

Damiano Cirri
Tanja Schirmeister
Ean-Jeong Seo
Thomas Efferth
Lara Massai
Luigi Messori
Nicola Micale

Zeitschrift

Molecules

Artikelnummer

19

Paginierung

4454 - 4454

Datum der Veröffentlichung

2020

Herausgeber

Multidisciplinary Digital Publishing Institute

Datum der Datenerfassung

2021

Titel

Antiproliferative Properties of a Few Auranofin-Related Gold (I) and Silver (I) Complexes in Leukemia Cells and their Interferences with the Ubiquitin Proteasome System

Sub types

article

Ausgabe der Zeitschrift

25

Datenquelle: Manual

Antiproliferative Properties of a Few Auranofin-Related Gold (I) and Silver (I) Complexes in Leukemia Cells and their Interferences with the Ubiquitin Proteasome System

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