J 2023

N-Indolyl diiron vinyliminium complexes exhibit antiproliferative effects in cancer cells associated with disruption of mitochondrial homeostasis, ROS scavenging, and antioxidant activity

BRESCIANI, Giulio, Jakub ČERVINKA, Hana KOSTRHUNOVÁ, Lorenzo BIANCALANA, Marco BORTOLUZZI et. al.

Základní údaje

Originální název

N-Indolyl diiron vinyliminium complexes exhibit antiproliferative effects in cancer cells associated with disruption of mitochondrial homeostasis, ROS scavenging, and antioxidant activity

Autoři

BRESCIANI, Giulio (380 Itálie), Jakub ČERVINKA (203 Česká republika, domácí), Hana KOSTRHUNOVÁ (203 Česká republika), Lorenzo BIANCALANA (380 Itálie), Marco BORTOLUZZI (380 Itálie), Guido PAMPALONI (380 Itálie), Vojtěch NOVOHRADSKÝ (203 Česká republika), Viktor BRABEC (203 Česká republika), Fabio MARCHETTI (380 Itálie) a Jana KAŠPÁRKOVÁ (203 Česká republika)

Vydání

Chemico-Biological Interactions, Elsevier B.V, 2023, 0009-2797

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

Impakt faktor

Impact factor: 5.100 v roce 2022

Kód RIV

RIV/00216224:14310/23:00132046

Organizační jednotka

Přírodovědecká fakulta

UT WoS

001094243700001

Klíčová slova anglicky

Diiron complexes; Indole; Anticancer; Mitochondria; ROS; Antioxidant

Štítky

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 5. 12. 2023 11:30, Mgr. Marie Šípková, DiS.

Anotace

V originále

The indole scaffold has been established as a key organic moiety for developing new drugs; on the other hand, a range of diiron bis-cyclopentadienyl complexes have recently emerged for their promising anticancer potential. Here, we report the synthesis of novel diiron complexes with an indole-functionalized vinyliminium ligand (2–5) and an indole-lacking analogue for comparative purposes (6), which were characterized by analytical and spectroscopic techniques. Complexes 2–6 are substantially stable in DMSO‑d6 and DMEM-d solutions at 37 °C (8% average degradation after 48 h) and display a balanced hydrophilic/lipophilic behaviour (LogPow values in the range −0.32 to 0.47), associated with appreciable water solubility. The complexes display selective antiproliferative potency towards several cancer cells in monolayer cultures, mainly in the low micromolar range, with reduced toxicity towards noncancerous epithelial cells. Thus, the cytotoxicity of the complexes is comparable to or better than clinically used metallopharmaceutical cisplatin. Comparing the antiproliferative activity obtained for complexes containing different ligands, we confirmed the importance of the indolyl group in the mechanism of antiproliferative activity of these complexes. Cell-based mechanistic studies suggest that the investigated diiron vinyliminium complexes (DVCs) show cytostatic rather than cytotoxic effects and subsequently induce a population of cells to undergo apoptosis. Furthermore, the molecular mechanism of action involves interactions with mitochondrial DNA and proteins, the reactive oxygen species (ROS)-scavenging properties and antioxidant activity of these complexes in cancer cells. This study highlights the importance of DVCs to their cancer cell activity and reinforces their prospective therapeutic potential as anticancer agents.