Issue 29, 2016

Pyrithione-based ruthenium complexes as inhibitors of aldo–keto reductase 1C enzymes and anticancer agents

Abstract

Four ruthenium complexes of clinically used zinc ionophore pyrithione and its oxygen analog 2-hydroxypyridine N-oxide were prepared and evaluated as inhibitors of enzymes of the aldo–keto reductase subfamily 1C (AKR1C). A kinetic study assisted with docking simulations showed a mixed type of inhibition consisting of a fast reversible and a slow irreversible step in the case of both organometallic compounds 1A and 1B. Both compounds also showed a remarkable selectivity towards AKR1C1 and AKR1C3 which are targets for breast cancer drug design. The organoruthenium complex of ligand pyrithione as well as pyrithione itself also displayed toxicity on the hormone-dependent MCF-7 breast cancer cell line with EC50 values in the low micromolar range.

Graphical abstract: Pyrithione-based ruthenium complexes as inhibitors of aldo–keto reductase 1C enzymes and anticancer agents

Supplementary files

Article information

Article type
Paper
Submitted
19 Feb 2016
Accepted
20 Jun 2016
First published
20 Jun 2016
This article is Open Access
Creative Commons BY license

Dalton Trans., 2016,45, 11791-11800

Author version available

Pyrithione-based ruthenium complexes as inhibitors of aldo–keto reductase 1C enzymes and anticancer agents

J. Kljun, M. Anko, K. Traven, M. Sinreih, R. Pavlič, Š. Peršič, Ž. Ude, E. E. Codina, J. Stojan, T. Lanišnik Rižner and I. Turel, Dalton Trans., 2016, 45, 11791 DOI: 10.1039/C6DT00668J

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