Platinum(IV) Derivatives of [Pt(1<i>S</i>,2<i>S</i>-diaminocyclohexane)(5,6-dimethyl-1,10-phenanthroline)] with Diclofenac Ligands in the Axial Positions: A New Class of Potent Multi-action Agents Exhibiting Selectivity to Cancer Cells

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F23%3A00583634" target="_blank" >RIV/68081707:_____/23:00583634 - isvavai.cz</a>

Výsledek na webu

<a href="https://pubs.acs.org/doi/10.1021/acs.jmedchem.3c00269" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.jmedchem.3c00269</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jmedchem.3c00269" target="_blank" >10.1021/acs.jmedchem.3c00269</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Platinum(IV) Derivatives of [Pt(1<i>S</i>,2<i>S</i>-diaminocyclohexane)(5,6-dimethyl-1,10-phenanthroline)] with Diclofenac Ligands in the Axial Positions: A New Class of Potent Multi-action Agents Exhibiting Selectivity to Cancer Cells

Popis výsledku v původním jazyce

The platinum(II) complex [Pt(1S,2S-diaminocyclohexane)(5,6-dimethyl-1,10-phenanthroline)](2+) (Pt(II)56MeSS, 1) exhibits high potencyacross numerous cancer cell lines acting by a multimodal mechanism.However, 1 also displays side toxicity and in vivo activity,all details of its mechanism of action are not entirely clear. Here,we describe the synthesis and biological properties of new platinum(IV)prodrugs that combine 1 with one or two axially coordinatedmolecules of diclofenac (DCF), a non-steroidal anti-inflammatory cancer-selectivedrug. The results suggest that these Pt(IV) complexes exhibit mechanismsof action typical for Pt(II) complex 1 and DCF, simultaneously.The presence of DCF ligand(s) in the Pt(IV) complexes promotes theantiproliferative activity and selectivity of 1 by inhibitinglactate transporters, resulting in blockage of the glycolytic processand impairment of mitochondrial potential. Additionally, the investigatedPt(IV) complexes selectively induce cell death in cancer cells, andthe Pt(IV) complexes containing DCF ligands induce hallmarks of immunogeniccell death in cancer cells.

Název v anglickém jazyce

Platinum(IV) Derivatives of [Pt(1<i>S</i>,2<i>S</i>-diaminocyclohexane)(5,6-dimethyl-1,10-phenanthroline)] with Diclofenac Ligands in the Axial Positions: A New Class of Potent Multi-action Agents Exhibiting Selectivity to Cancer Cells

Popis výsledku anglicky

The platinum(II) complex [Pt(1S,2S-diaminocyclohexane)(5,6-dimethyl-1,10-phenanthroline)](2+) (Pt(II)56MeSS, 1) exhibits high potencyacross numerous cancer cell lines acting by a multimodal mechanism.However, 1 also displays side toxicity and in vivo activity,all details of its mechanism of action are not entirely clear. Here,we describe the synthesis and biological properties of new platinum(IV)prodrugs that combine 1 with one or two axially coordinatedmolecules of diclofenac (DCF), a non-steroidal anti-inflammatory cancer-selectivedrug. The results suggest that these Pt(IV) complexes exhibit mechanismsof action typical for Pt(II) complex 1 and DCF, simultaneously.The presence of DCF ligand(s) in the Pt(IV) complexes promotes theantiproliferative activity and selectivity of 1 by inhibitinglactate transporters, resulting in blockage of the glycolytic processand impairment of mitochondrial potential. Additionally, the investigatedPt(IV) complexes selectively induce cell death in cancer cells, andthe Pt(IV) complexes containing DCF ligands induce hallmarks of immunogeniccell death in cancer cells.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10402 - Inorganic and nuclear chemistry

Projekt

<a href="/cs/project/GA21-27514S" target="_blank" >GA21-27514S: Sloučeniny kovů pro zvýšenou imunoterapii rakoviny</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

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

Název periodika

Journal of Medicinal Chemistry

ISSN

0022-2623

e-ISSN

1520-4804

Svazek periodika

66

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

15

Strana od-do

7894-7908

Kód UT WoS článku

001006562300001

EID výsledku v databázi Scopus

2-s2.0-85163517797