A Dogma in Doubt: Hydrolysis of Equatorial Ligands of Pt-IV Complexes under Physiological Conditions

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11320%2F19%3A10405718" target="_blank" >RIV/00216208:11320/19:10405718 - isvavai.cz</a>

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=KWszAH.q5P" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=KWszAH.q5P</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/anie.201900682" target="_blank" >10.1002/anie.201900682</a>

Jazyk výsledku

angličtina

Název v původním jazyce

A Dogma in Doubt: Hydrolysis of Equatorial Ligands of Pt-IV Complexes under Physiological Conditions

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

A Dogma in Doubt: Hydrolysis of Equatorial Ligands of Pt-IV Complexes under Physiological Conditions

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10301 - Atomic, molecular and chemical physics (physics of atoms and molecules including collision, interaction with radiation, magnetic resonances, Mössbauer effect)

Projekt

<a href="/cs/project/GA16-06240S" target="_blank" >GA16-06240S: Struktura a dynamika organokovových komplexů v biologickém prostředí.</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Angewandte Chemie - International Edition

ISSN

1433-7851

e-ISSN

—

Svazek periodika

58

Číslo periodika v rámci svazku

22

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

6

Strana od-do

7464-7469

Kód UT WoS článku

000474803100051

EID výsledku v databázi Scopus

2-s2.0-85065024407