Exploring the Antitumor Potential of Copper Complexes Based on Ester Derivatives of Bis(pyrazol-1-yl)acetate Ligands

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11320%2F22%3A10457096" target="_blank" >RIV/00216208:11320/22:10457096 - isvavai.cz</a>

Výsledek na webu

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

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/ijms23169397" target="_blank" >10.3390/ijms23169397</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Exploring the Antitumor Potential of Copper Complexes Based on Ester Derivatives of Bis(pyrazol-1-yl)acetate Ligands

Popis výsledku v původním jazyce

Bis(pyrazol-1-yl)acetic acid (HC(pz)(2)COOH) and bis(3,5-dimethyl-pyrazol-1-yl)acetic acid (HC(pz(Me2))(2)COOH) were converted into the methyl ester derivatives 1 (L-OMe) and 2 (L-2OMe), respectively, and were used for the preparation of Cu(I) and Cu(II) complexes 3-10. The copper(II) complexes were prepared by the reaction of CuCl2 center dot 2H(2)O or CuBr2 with ligands 1 and 2 in methanol solution. The copper(I) complexes were prepared by the reaction of Cu[(CH3CN)(4)]PF6 and 1,3,5-triaza-7-phosphaadamantane (PTA) or triphenylphosphine with L-OMe and L-2OMe in acetonitrile solution. Synchrotron radiation-based complementary techniques (XPS, NEXAFS, and XAS) were used to investigate the electronic and molecular structures of the complexes and the local structure around copper ions in selected Cu(I) and Cu(II) coordination compounds. All Cu(I) and Cu(II) complexes showed a significant in vitro antitumor activity, proving to be more effective than the reference drug cisplatin in a panel of human cancer cell lines, and were able to overcome cisplatin resistance. Noticeably, Cu complexes appeared much more effective than cisplatin in 3D spheroid cultures. Mechanistic studies revealed that the antitumor potential did not correlate with cellular accumulation but was consistent with intracellular targeting of PDI, ER stress, and paraptotic cell death induction.

Název v anglickém jazyce

Exploring the Antitumor Potential of Copper Complexes Based on Ester Derivatives of Bis(pyrazol-1-yl)acetate Ligands

Popis výsledku anglicky

Bis(pyrazol-1-yl)acetic acid (HC(pz)(2)COOH) and bis(3,5-dimethyl-pyrazol-1-yl)acetic acid (HC(pz(Me2))(2)COOH) were converted into the methyl ester derivatives 1 (L-OMe) and 2 (L-2OMe), respectively, and were used for the preparation of Cu(I) and Cu(II) complexes 3-10. The copper(II) complexes were prepared by the reaction of CuCl2 center dot 2H(2)O or CuBr2 with ligands 1 and 2 in methanol solution. The copper(I) complexes were prepared by the reaction of Cu[(CH3CN)(4)]PF6 and 1,3,5-triaza-7-phosphaadamantane (PTA) or triphenylphosphine with L-OMe and L-2OMe in acetonitrile solution. Synchrotron radiation-based complementary techniques (XPS, NEXAFS, and XAS) were used to investigate the electronic and molecular structures of the complexes and the local structure around copper ions in selected Cu(I) and Cu(II) coordination compounds. All Cu(I) and Cu(II) complexes showed a significant in vitro antitumor activity, proving to be more effective than the reference drug cisplatin in a panel of human cancer cell lines, and were able to overcome cisplatin resistance. Noticeably, Cu complexes appeared much more effective than cisplatin in 3D spheroid cultures. Mechanistic studies revealed that the antitumor potential did not correlate with cellular accumulation but was consistent with intracellular targeting of PDI, ER stress, and paraptotic cell death induction.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10305 - Fluids and plasma physics (including surface physics)

Projekt

—

Návaznosti

—

Rok uplatnění

2022

Kód důvěrnosti údajů

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

Název periodika

International Journal of Molecular Sciences

ISSN

1661-6596

e-ISSN

1422-0067

Svazek periodika

23

Číslo periodika v rámci svazku

16

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

26

Strana od-do

9397

Kód UT WoS článku

000845778800001

EID výsledku v databázi Scopus

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