Back to Search Start Over

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

Authors :
Damiano Cirri
Tanja Schirmeister
Ean-Jeong Seo
Thomas Efferth
Lara Massai
Luigi Messori
Nicola Micale
Source :
Molecules, Vol 25, Iss 19, p 4454 (2020)
Publication Year :
2020
Publisher :
MDPI AG, 2020.

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.

Details

Language :
English
ISSN :
14203049
Volume :
25
Issue :
19
Database :
Directory of Open Access Journals
Journal :
Molecules
Publication Type :
Academic Journal
Accession number :
edsdoj.784fdd9d0c6e4dd39a8f71a3f591d04b
Document Type :
article
Full Text :
https://doi.org/10.3390/molecules25194454