Biscarbene gold(i) complexes

Structure-activity-relationships regarding antibacterial effects, cytotoxicity, TrxR inhibition and cellular bioavailability

authored by

Claudia Schmidt, Bianka Karge, Rainer Misgeld, Aram Prokop, Mark Brönstrup, Ingo Ott

Abstract

A series of gold(i) complexes with two N-heterocyclic carbene ligands (biscarbene gold complexes) were prepared and evaluated for their effects against cancer cells and pathogenic bacteria. Proliferation inhibition was observed in cancer cells and in Gram-positive bacteria, whereas Gram-negative bacteria were less sensitive towards the compounds. The protein binding and cellular uptake were quantified and the combined results indicated a strong correlation between cellular bioavailability and antiproliferative effects. The biscarbene gold complexes inhibited bacterial and mammalian TrxRs with low to moderate potency. However, based on the obtained structure-activity-relationships and the high cellular accumulation levels, TrxR inhibition can be considered as a relevant contributor to the cellular pharmacology of biscarbene gold(i) complexes.

External Organisation(s)

Technische Universität Braunschweig
University of Cologne
German Center for Infection Research (DZIF)

Type

Article

Journal

MEDCHEMCOMM

Volume

8

Pages

1681-1689

No. of pages

9

ISSN

2040-2503

Publication date

06.2017

Publication status

Published

Peer reviewed

Yes

ASJC Scopus subject areas

Biochemistry, Molecular Medicine, Pharmacology, Pharmaceutical Science, Drug Discovery, Organic Chemistry

Sustainable Development Goals

SDG 3 - Good Health and Well-being

Electronic version(s)

https://doi.org/10.1039/c7md00269f (Access: Closed)
https://europepmc.org/article/PMC/6072206 (Access: Open)