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
The result's identifiers
Result code in 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>
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
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
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10402 - Inorganic and nuclear chemistry
Result continuities
Project
<a href="/en/project/GA21-27514S" target="_blank" >GA21-27514S: Metal-based compounds for enhanced cancer immunotherapy</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Medicinal Chemistry
ISSN
0022-2623
e-ISSN
1520-4804
Volume of the periodical
66
Issue of the periodical within the volume
12
Country of publishing house
US - UNITED STATES
Number of pages
15
Pages from-to
7894-7908
UT code for WoS article
001006562300001
EID of the result in the Scopus database
2-s2.0-85163517797