Platinum(IV) Derivatives of [Pt(1iS/i,2iS/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

Kostrhunová, Hana; McGhie, B. S.; Marková, Lenka; Nováková, Olga; Kašpárková, Jana; Aldrich-Wright, J.R.; Brabec, Viktor

doi:https://dx.doi.org/10.1021/acs.jmedchem.3c00269

Number of the records: 1

Platinum(IV) Derivatives of [Pt(1iS/i,2iS/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

1.

SYSNO ASEP	0583634
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Platinum(IV) Derivatives of [Pt(1iS/i,2iS/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
Author(s)	Kostrhunová, Hana (BFU-R)_{RID, ORCID} McGhie, B. S. (AU) Marková, Lenka (BFU-R)_ORCID Nováková, Olga (BFU-R)_{RID, ORCID} Kašpárková, Jana (BFU-R)_{RID, ORCID} Aldrich-Wright, J.R. (AU) Brabec, Viktor (BFU-R)_{RID, ORCID}
Number of authors	7
Source Title	Journal of Medicinal Chemistry. - : American Chemical Society - ISSN 0022-2623 Roč. 66, č. 12 (2023), s. 7894-7908
Number of pages	15 s.
Publication form	Print - P
Language	eng - English
Country	US - United States
Keywords	cyclooxygenase inhibitors ; anticancer activity ; in-vitro ; death ; complexes ; mechanism ; cisplatin ; mitochondrial ; cytotoxicity
Subject RIV	FR - Pharmacology ; Medidal Chemistry
OECD category	Inorganic and nuclear chemistry
R&D Projects	GA21-27514S GA ČR - Czech Science Foundation (CSF)
Method of publishing	Open access
Institutional support	BFU-R - RVO:68081707
UT WOS	001006562300001
EID SCOPUS	85163517797
DOI	10.1021/acs.jmedchem.3c00269
Annotation	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.
Workplace	Institute of Biophysics
Contact	Jana Poláková, polakova@ibp.cz, Tel.: 541 517 244
Year of Publishing	2024
Electronic address	https://pubs.acs.org/doi/10.1021/acs.jmedchem.3c00269

Number of the records: 1