Header

UZH-Logo

Maintenance Infos

Organometallic rhenium complexes divert doxorubicin to the mitochondria


Imstepf, Sebastian; Pierroz, Vanessa; Rubbiani, Riccardo; Felber, Michael; Fox, Thomas; Gasser, Gilles; Alberto, Roger (2016). Organometallic rhenium complexes divert doxorubicin to the mitochondria. Angewandte Chemie Internationale Edition, 55(8):2792-2795.

Abstract

Doxorubicin, a well-established chemotherapeutic agent, is known to accumulate in the cell nucleus. By using ICP-MS, we show that the conjugation of two small organometallic rhenium complexes to this structural motif results in a significant redirection of the conjugates from the nucleus to the mitochondria. Despite this relocation, the two bioconjugates display excellent toxicity toward HeLa cells. In addition, we carried out a preliminarily investigation of aspects of cytotoxicity and present evidence that the conjugates disrupt the mitochondrial membrane potential, are strong inhibitors of human Topoisomerase II, and induce apoptosis. Such derivatives may enhance the therapeutic index of the aggressive parent drug and overcome drug resistance by influencing nuclear and mitochondrial homeostasis.

Abstract

Doxorubicin, a well-established chemotherapeutic agent, is known to accumulate in the cell nucleus. By using ICP-MS, we show that the conjugation of two small organometallic rhenium complexes to this structural motif results in a significant redirection of the conjugates from the nucleus to the mitochondria. Despite this relocation, the two bioconjugates display excellent toxicity toward HeLa cells. In addition, we carried out a preliminarily investigation of aspects of cytotoxicity and present evidence that the conjugates disrupt the mitochondrial membrane potential, are strong inhibitors of human Topoisomerase II, and induce apoptosis. Such derivatives may enhance the therapeutic index of the aggressive parent drug and overcome drug resistance by influencing nuclear and mitochondrial homeostasis.

Statistics

Citations

14 citations in Web of Science®
14 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

1 download since deposited on 04 Aug 2016
1 download since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Language:English
Date:18 February 2016
Deposited On:04 Aug 2016 07:11
Last Modified:21 Nov 2017 18:33
Publisher:Wiley-VCH Verlag
ISSN:1433-7851
Publisher DOI:https://doi.org/10.1002/anie.201511432
PubMed ID:26799241

Download