Lysosome-Targeting Amplifiers of Reactive Oxygen Species as Anticancer Prodrugs

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389030%3A_____%2F17%3A00485730" target="_blank" >RIV/61389030:_____/17:00485730 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1002/anie.201706585" target="_blank" >http://dx.doi.org/10.1002/anie.201706585</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/anie.201706585" target="_blank" >10.1002/anie.201706585</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Lysosome-Targeting Amplifiers of Reactive Oxygen Species as Anticancer Prodrugs

Popis výsledku v původním jazyce

Cancer cells produce elevated levels of reactive oxygen species, which has been used to design cancer specific prodrugs. Their activation relies on at least a bimolecular process, in which a prodrug reacts with ROS. However, at low micromolar concentrations of the prodrugs and ROS, the activation is usually inefficient. Herein, we propose and validate a potentially general approach for solving this intrinsic problem of ROS-dependent prodrugs. In particular, known prodrug 4-(N-ferrocenyl-N-benzylaminocarbonyloxymethyl)phenylboronic acid pinacol ester was converted into its lysosome-specific analogue. Since lysosomes contain a higher concentration of active ROS than the cytoplasm, activation of the prodrug was facilitated with respect to the parent compound. Moreover, it was found to exhibit high anticancer activity in a variety of cancer cell lines (IC 50 =3.5–7.2 μm) and in vivo (40 mg kg −1 , NK/Ly murine model) but remained weakly toxic towards non-malignant cells (IC 50 =15–30 μm).

Název v anglickém jazyce

Lysosome-Targeting Amplifiers of Reactive Oxygen Species as Anticancer Prodrugs

Popis výsledku anglicky

Cancer cells produce elevated levels of reactive oxygen species, which has been used to design cancer specific prodrugs. Their activation relies on at least a bimolecular process, in which a prodrug reacts with ROS. However, at low micromolar concentrations of the prodrugs and ROS, the activation is usually inefficient. Herein, we propose and validate a potentially general approach for solving this intrinsic problem of ROS-dependent prodrugs. In particular, known prodrug 4-(N-ferrocenyl-N-benzylaminocarbonyloxymethyl)phenylboronic acid pinacol ester was converted into its lysosome-specific analogue. Since lysosomes contain a higher concentration of active ROS than the cytoplasm, activation of the prodrug was facilitated with respect to the parent compound. Moreover, it was found to exhibit high anticancer activity in a variety of cancer cell lines (IC 50 =3.5–7.2 μm) and in vivo (40 mg kg −1 , NK/Ly murine model) but remained weakly toxic towards non-malignant cells (IC 50 =15–30 μm).

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2017

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

56

Číslo periodika v rámci svazku

49

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

5

Strana od-do

15545-15549

Kód UT WoS článku

000416244200006

EID výsledku v databázi Scopus

2-s2.0-85033445233