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

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; Alba HERNÁNDEZ-GARCÍA; Delia BAUTISTA; Lenka MARKOVÁ; Hana KOSTRHUNOVÁ; Jaroslav MALINA; Jana KAŠPÁRKOVÁ; M Dolores SANTANA; Viktor BRABEC a José RUIZ

Vydání

Inorganic Chemistry Frontiers, Royal Society of 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

URL

Impakt faktor

Impact factor: 6.400

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/24:00136068

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

metallodrugs; oncosis; anticancer therapy

Štítky

14313050, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 18. 3. 2025 15:48, Mgr. Marie Novosadová Šípková, DiS.

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.

Citovat

ČERVINKA, Jakub; Alba HERNÁNDEZ-GARCÍA; Delia BAUTISTA; Lenka MARKOVÁ; Hana KOSTRHUNOVÁ; Jaroslav MALINA; Jana KAŠPÁRKOVÁ; M Dolores SANTANA; Viktor BRABEC a José RUIZ. New cyclometalated Ru(ii) polypyridyl photosensitizers trigger oncosis in cancer cells by inducing damage to cellular membranes. Inorganic Chemistry Frontiers. Royal Society of Chemistry, 2024, roč. 11, č. 13, s. 3855-3876. ISSN 2052-1553. Dostupné z: https://doi.org/10.1039/D4QI00732H.

@article{2405124,
   author = {Červinka, Jakub and HernándezandGarcía, Alba and Bautista, Delia and Marková, Lenka and Kostrhunová, Hana and Malina, Jaroslav and Kašpárková, Jana and Santana, M Dolores and Brabec, Viktor and Ruiz, José},
   article_number = {13},
   doi = {https://doi.org/10.1039/D4QI00732H},
   keywords = {metallodrugs; oncosis; anticancer therapy},
   language = {eng},
   issn = {2052-1553},
   journal = {Inorganic Chemistry Frontiers},
   title = {New cyclometalated Ru(ii) polypyridyl photosensitizers trigger oncosis in cancer cells by inducing damage to cellular membranes},
   url = {https://pubs.rsc.org/en/content/articlelanding/2024/qi/d4qi00732h},
   volume = {11},
   year = {2024}
}

TY  - JOUR
ID  - 2405124
AU  - Červinka, Jakub - Hernández-García, Alba - Bautista, Delia - Marková, Lenka - Kostrhunová, Hana - Malina, Jaroslav - Kašpárková, Jana - Santana, M Dolores - Brabec, Viktor - Ruiz, José
PY  - 2024
TI  - New cyclometalated Ru(ii) polypyridyl photosensitizers trigger oncosis in cancer cells by inducing damage to cellular membranes
JF  - Inorganic Chemistry Frontiers
VL  - 11
IS  - 13
SP  - 3855-3876
EP  - 3855-3876
PB  - Royal Society of Chemistry
SN  - 20521553
KW  - metallodrugs
KW  - oncosis
KW  - anticancer therapy
UR  - https://pubs.rsc.org/en/content/articlelanding/2024/qi/d4qi00732h
N2  - 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.
ER  -

ČERVINKA, Jakub; Alba HERNÁNDEZ-GARCÍA; Delia BAUTISTA; Lenka MARKOVÁ; Hana KOSTRHUNOVÁ; Jaroslav MALINA; Jana KAŠPÁRKOVÁ; M Dolores SANTANA; Viktor BRABEC a José RUIZ. New cyclometalated Ru(ii) polypyridyl photosensitizers trigger oncosis in cancer cells by inducing damage to cellular membranes. \textit{Inorganic Chemistry Frontiers}. Royal Society of Chemistry, 2024, roč.~11, č.~13, s.~3855-3876. ISSN~2052-1553. Dostupné z: https://doi.org/10.1039/D4QI00732H.

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