The Library
In-cell activation of organo-osmium(II) anticancer complexes
Tools
Tools
Tools
Needham, Russell J., Sanchez-Cano, Carlos, Zhang, Xin, Romero-Canelón, Isolda, Habtemariam, Abraha, Cooper, Margaret S., Meszaros, Levente, Clarkson, Guy J., Blower, Philip J. and Sadler, P. J. (2017) In-cell activation of organo-osmium(II) anticancer complexes. Angewandte Chemie International Edition, 56 (4). pp. 1017-1020. doi:10.1002/anie.201610290 ISSN 1433-7851.
|
PDF
WRAP-in-cell-activation-organo-osmium(II)-anticancer-complexes-Sadler-2017.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (1271Kb) | Preview |
Official URL: http://dx.doi.org/10.1002/anie.201610290
Abstract
The family of iodido OsII arene phenylazopyridine complexes [Os(η6 -p-cym)(5-R1-pyridylazo-4-R2 -phenyl))I]+ (where p-cym = para-cymene) exhibit potent sub-micromolar antiproliferative activity towards human cancer cells and are active in vivo. Their chemical behavior is distinct from that of cisplatin: they do not readily hydrolyze, nor bind to DNA bases. We report here a mechanism by which they are activated in cancer cells, involving release of the I- ligand in the presence of glutathione (GSH). The X-ray crystal structures of two active complexes are reported, 1-I (R1 = OEt, R2 = H) and 2-I (R1 = H, R2 = NMe2). They were labelled with the radionuclide 131I (β-/γ emitter, t1/2 8.02 d), and their activity in MCF-7 human breast cancer cells was studied. 1-[131I] and 2-[131I] exhibit good stability in both phosphate-buffered saline and blood serum. In contrast, once taken up by MCF-7 cells, the iodide ligand is rapidly pumped out. Intriguingly, GSH catalyzes their hydrolysis. The resulting hydroxido complexes can form thiolato and sulfenato adducts with GSH, and react with H2O2 generating hydroxyl radicals. These findings shed new light on the mechanism of action of these organo-osmium complexes.
| Item Type: | Journal Article | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Subjects: | Q Science > QD Chemistry Q Science > QP Physiology |
||||||||||||||||||||||||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | ||||||||||||||||||||||||||||||
| Library of Congress Subject Headings (LCSH): | Organoosmium compounds, Antineoplastic agents, Organometallic compounds -- Therapeutic use, Bioinorganic chemistry, Glutathione | ||||||||||||||||||||||||||||||
| Journal or Publication Title: | Angewandte Chemie International Edition | ||||||||||||||||||||||||||||||
| Publisher: | Wiley - V C H Verlag GmbH & Co. KGaA | ||||||||||||||||||||||||||||||
| ISSN: | 1433-7851 | ||||||||||||||||||||||||||||||
| Official Date: | 19 January 2017 | ||||||||||||||||||||||||||||||
| Dates: |
|
||||||||||||||||||||||||||||||
| Volume: | 56 | ||||||||||||||||||||||||||||||
| Number: | 4 | ||||||||||||||||||||||||||||||
| Page Range: | pp. 1017-1020 | ||||||||||||||||||||||||||||||
| DOI: | 10.1002/anie.201610290 | ||||||||||||||||||||||||||||||
| Status: | Peer Reviewed | ||||||||||||||||||||||||||||||
| Publication Status: | Published | ||||||||||||||||||||||||||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||||||||||||||||||||
| Date of first compliant deposit: | 6 April 2018 | ||||||||||||||||||||||||||||||
| Date of first compliant Open Access: | 9 April 2018 | ||||||||||||||||||||||||||||||
| RIOXX Funder/Project Grant: |
|
Request changes or add full text files to a record
Repository staff actions (login required)
 |
View Item |
Downloads
Downloads per month over past year
