A Comparative Analysis of the In Vitro Anticancer Activity of Iridium(III) {η 5 -C5Me4R} Complexes with Variable R Groups
2021
Authors:
De Palo, AliceDrača, Dijana
Murrali, Maria Grazia
Zacchini, Stefano
Pampaloni, Guido
Mijatović, Sanja
Maksimović-Ivanić, Danijela
Marchetti, Fabio
Document Type:
Article (Published version)
Metadata
Show full item recordAbstract:
Piano-stool iridium complexes based on the pentamethylcyclopentadienyl ligand (Cp*)
have been intensively investigated as anticancer drug candidates and hold much promise in this
setting. A systematic study aimed at outlining the effect of Cp* mono-derivatization on the an tiproliferative activity is presented here. Thus, the dinuclear complexes [Ir(η
5
-C5Me4R)Cl(µ-Cl)]2
(R = Me, 1a; R = H, 1b; R = Pr, 1c; R = 4-C6H4F, 1d; R = 4-C6H4OH, 1e), their 2-phenylpyridyl
mononuclear derivatives [Ir(η
5
-C5Me4R)(kN,kCPhPy)Cl] (2a–d), and the dimethylsulfoxide complex
[Ir{η
5
-C5Me4
(4-C6H4OH)}Cl2
(κS-Me2S=O)] (3) were synthesized, structurally characterized, and
assessed for their cytotoxicity towards a panel of six human and rodent cancer cell lines (mouse
melanoma, B16; rat glioma, C6; breast adenocarcinoma, MCF-7; colorectal carcinoma, SW620 and
HCT116; ovarian carcinoma, A2780) and one primary, human fetal lung fibroblast cell line (MRC5).
Complexes 2b (R = H) and 2d (4-C6H4F) emerged as the most active ones and were selected for further
investigation. They did not affect the viability of primary mouse peritoneal cells, and their tumorici dal action arises from the combined influence on cellular proliferation, apoptosis and senescence. The
latter is triggered by mitochondrial failure and production of reactive oxygen and nitrogen species.
Keywords:
bioorganometallic chemistry; organoiridium complexes;; cytotoxicity; apoptosis; senescence; cell proliferationSource:
International Journal of Molecular Sciences, 2021, 22, 14, 7422-Funding / projects:
- University of Pisa (PRA_2020_39)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
DOI: 10.3390/ijms22147422
ISSN: 1422-0067
PubMed: 34299041