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A Dogma in Doubt: Hydrolysis of Equatorial Ligands of Pt(IV) Complexes under Physiological Conditions
Due to their high kinetic inertness and consequently reduced side reactions with biomolecules, Pt(IV) complexes are considered to define the future of anticancer platinum drugs. The aqueous stability of a series of biscarboxylato Pt(IV) complexes was studied under physiologically relevant conditions...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766845/ https://www.ncbi.nlm.nih.gov/pubmed/30870571 http://dx.doi.org/10.1002/anie.201900682 |
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author | Kastner, Alexander Poetsch, Isabella Mayr, Josef Burda, Jaroslav V. Roller, Alexander Heffeter, Petra Keppler, Bernhard K. Kowol, Christian R. |
author_facet | Kastner, Alexander Poetsch, Isabella Mayr, Josef Burda, Jaroslav V. Roller, Alexander Heffeter, Petra Keppler, Bernhard K. Kowol, Christian R. |
author_sort | Kastner, Alexander |
collection | PubMed |
description | Due to their high kinetic inertness and consequently reduced side reactions with biomolecules, Pt(IV) complexes are considered to define the future of anticancer platinum drugs. The aqueous stability of a series of biscarboxylato Pt(IV) complexes was studied under physiologically relevant conditions. Unexpectedly and in contrast to the current chemical understanding, especially oxaliplatin and satraplatin complexes underwent fast hydrolysis in equatorial position (even in cell culture medium and serum). Notably, the resulting hydrolysis products strongly differ in their reduction kinetics, a crucial parameter for the activation of Pt(IV) drugs, which also changes the anticancer potential of the compounds in cell culture. The discovery that intact Pt(IV) complexes can hydrolyze at equatorial position contradicts the dogma on the general kinetic inertness of Pt(IV) compounds and needs to be considered in the screening and design for novel platinum‐based anticancer drugs. |
format | Online Article Text |
id | pubmed-6766845 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-67668452019-10-01 A Dogma in Doubt: Hydrolysis of Equatorial Ligands of Pt(IV) Complexes under Physiological Conditions Kastner, Alexander Poetsch, Isabella Mayr, Josef Burda, Jaroslav V. Roller, Alexander Heffeter, Petra Keppler, Bernhard K. Kowol, Christian R. Angew Chem Int Ed Engl Communications Due to their high kinetic inertness and consequently reduced side reactions with biomolecules, Pt(IV) complexes are considered to define the future of anticancer platinum drugs. The aqueous stability of a series of biscarboxylato Pt(IV) complexes was studied under physiologically relevant conditions. Unexpectedly and in contrast to the current chemical understanding, especially oxaliplatin and satraplatin complexes underwent fast hydrolysis in equatorial position (even in cell culture medium and serum). Notably, the resulting hydrolysis products strongly differ in their reduction kinetics, a crucial parameter for the activation of Pt(IV) drugs, which also changes the anticancer potential of the compounds in cell culture. The discovery that intact Pt(IV) complexes can hydrolyze at equatorial position contradicts the dogma on the general kinetic inertness of Pt(IV) compounds and needs to be considered in the screening and design for novel platinum‐based anticancer drugs. John Wiley and Sons Inc. 2019-04-25 2019-05-27 /pmc/articles/PMC6766845/ /pubmed/30870571 http://dx.doi.org/10.1002/anie.201900682 Text en © 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Communications Kastner, Alexander Poetsch, Isabella Mayr, Josef Burda, Jaroslav V. Roller, Alexander Heffeter, Petra Keppler, Bernhard K. Kowol, Christian R. A Dogma in Doubt: Hydrolysis of Equatorial Ligands of Pt(IV) Complexes under Physiological Conditions |
title | A Dogma in Doubt: Hydrolysis of Equatorial Ligands of Pt(IV) Complexes under Physiological Conditions |
title_full | A Dogma in Doubt: Hydrolysis of Equatorial Ligands of Pt(IV) Complexes under Physiological Conditions |
title_fullStr | A Dogma in Doubt: Hydrolysis of Equatorial Ligands of Pt(IV) Complexes under Physiological Conditions |
title_full_unstemmed | A Dogma in Doubt: Hydrolysis of Equatorial Ligands of Pt(IV) Complexes under Physiological Conditions |
title_short | A Dogma in Doubt: Hydrolysis of Equatorial Ligands of Pt(IV) Complexes under Physiological Conditions |
title_sort | dogma in doubt: hydrolysis of equatorial ligands of pt(iv) complexes under physiological conditions |
topic | Communications |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766845/ https://www.ncbi.nlm.nih.gov/pubmed/30870571 http://dx.doi.org/10.1002/anie.201900682 |
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