J 2024

New cyclometalated Ru(ii) polypyridyl photosensitizers trigger oncosis in cancer cells by inducing damage to cellular membranes

ČERVINKA, Jakub, Alba HERNÁNDEZ-GARCÍA, Delia BAUTISTA, Lenka MARKOVÁ, Hana KOSTRHUNOVÁ et. al.

Základní údaje

Originální název

New cyclometalated Ru(ii) polypyridyl photosensitizers trigger oncosis in cancer cells by inducing damage to cellular membranes

Autoři

ČERVINKA, Jakub (203 Česká republika, domácí), Alba HERNÁNDEZ-GARCÍA (724 Španělsko), Delia BAUTISTA (724 Španělsko), Lenka MARKOVÁ (203 Česká republika, domácí), Hana KOSTRHUNOVÁ (203 Česká republika, domácí), Jaroslav MALINA (203 Česká republika), Jana KAŠPÁRKOVÁ (203 Česká republika, domácí), M Dolores SANTANA (724 Španělsko), Viktor BRABEC (203 Česká republika, domácí) a José RUIZ (756 Švýcarsko)

Vydání

INORGANIC CHEMISTRY FRONTIERS, ENGLAND, ROYAL SOC CHEMISTRY, 2024, 2052-1553

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

Impakt faktor

Impact factor: 7.000 v roce 2022

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

metallodrugs; oncosis; anticancer therapy

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 27. 5. 2024 16:03, Mgr. Jakub Červinka

Anotace

V originále

A new generation series of cyclometalated Ru(II) polypyridyl complexes of the type [Ru(C^N)(N^N)2]+, Ru1–Ru4, were rationally designed and synthesized, where N^N = 2,2′-bipyridine (bpy) and dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq) and C^N = deprotonated methyl 1-butyl-2-aryl-benzimidazolecarboxylate with p-CF3C6H4 or p-Me2NC6H4 substituents in the R3 position of the phenyl ring. The photophysical properties of Ru1–Ru4 revealed absorption maxima around 560 nm with an absorption up to 700 nm. The new Ru complexes were able to generate singlet oxygen (1O2) upon green light irradiation in acetonitrile, with complexes containing the CF3 group, Ru1 and Ru3, being the best performers. Furthermore, Ru1 and Ru3 were also able to photogenerate hydroxyl radicals OH˙. By having PSs capable of undergoing both type I and type II mechanisms, a broader range of cytotoxic effects is achieved. Ru1–Ru4 accumulated in membrane-rich compartments, including the cytoplasmic membrane, mitochondria, and endoplasmic reticulum in HeLa cells. Upon irradiation of Ru1 with green light, all these compartments were damaged in treated cells. Based on in vitro experiments, we deduced that the compound Ru1 under irradiation has the capability to disrupt phospholipid membranes directly. Additionally, differential scanning calorimetry of living cells also indicated damage of cytoplasmic/membrane proteins, ultimately leading to cell death via oncosis.