A Novel Benzothiazole-1,2,3-Triazole-Based Arene Osmium(II)
Complex as an Effective Rhabdomyosarcoma Cancer Stem Cell Agent

J 2025

A Novel Benzothiazole-1,2,3-Triazole-Based Arene Osmium(II) Complex as an Effective Rhabdomyosarcoma Cancer Stem Cell Agent

SHARKAWY, Sofia; Alba HERNÁNDEZ-GARCÍA; Hana KOSTRHUNOVÁ; Delia BAUTISTA; Lenka MARKOVÁ et. al.

Základní údaje

Originální název

A Novel Benzothiazole-1,2,3-Triazole-Based Arene Osmium(II) Complex as an Effective Rhabdomyosarcoma Cancer Stem Cell Agent

Autoři

SHARKAWY, Sofia (703 Slovensko, domácí); Alba HERNÁNDEZ-GARCÍA (724 Španělsko); Hana KOSTRHUNOVÁ (203 Česká republika); Delia BAUTISTA (724 Španělsko); Lenka MARKOVÁ (203 Česká republika); María Dolores SANTANA (724 Španělsko); Jana KAŠPÁRKOVÁ (203 Česká republika); Viktor BRABEC (203 Česká republika) a José RUIZ (724 Španělsko)

Vydání

Inorganic Chemistry Frontiers, Royal Society of Chemistry, 2025, 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: 6.100 v roce 2023

Organizační jednotka

Přírodovědecká fakulta

DOI

http://dx.doi.org/10.1039/D4QI02737J

UT WoS

001397563900001

EID Scopus

2-s2.0-85215704168

Klíčová slova anglicky

BOVINE SERUM-ALBUMIN; BINDING; RUTHENIUM(II); ANTITUMOR; INHIBITION; WARFARIN; LIGANDS; ANALOGS; GROWTH

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 22. 5. 2025 10:01, Mgr. Marie Novosadová Šípková, DiS.

Anotace

V originále

We designed a series of pseudo-octahedral arene Os(II) complexes (Os1–Os5) with the general formula [(η6-p-cym)Os(BTAT)Cl]+, where BTAT represents chelating N^N′ ligands based on the 1-aryl-4-benzothiazolyl-1,2,3-triazole scaffold. The structures of Os3 and Os5 were confirmed by X-ray diffraction, and Os5 exhibits a bathochromic shift in its absorption band compared to the other complexes, likely due to the electron-donating properties of the substituent NMe2. Os5 also hydrolyzed without losing its BTAT ligand and exhibited the highest cellular accumulation in Rhabdomyosarcoma (RD) cancer cells. The investigated Os(II) complexes demonstrated moderate antiproliferative activity across six cancer cell lines, with Os5 being the most potent, showing activity comparable to or better than conventional cisplatin. Cellular accumulation was a key factor influencing their antiproliferative effect, though binding to human serum albumin did not play a significant role. Further studies with Os5 in RD cells, the most responsive cell line, revealed that its mechanism of action includes mitochondrial dysfunction, apoptosis via a caspase-dependent pathway, and cell cycle arrest at the G1 phase. Os5 also increased the production/generation of reactive oxygen species (ROS) in RD cells, implicating ROS production as a contributor to its activity. Importantly, Os5 was effective against cancer stem cells (CSCs) in 3D spheroid models, marking the first report of an osmium-based compound targeting CSC-enriched RD cells. This highlights the potential of Os5 as a CSC-targeted therapy, addressing the need for treatments that prevent relapse and metastasis. The study underscores the promising role of metal-based complexes in cancer stem cell chemotherapy.

Citovat

SHARKAWY, Sofia; Alba HERNÁNDEZ-GARCÍA; Hana KOSTRHUNOVÁ; Delia BAUTISTA; Lenka MARKOVÁ; María Dolores SANTANA; Jana KAŠPÁRKOVÁ; Viktor BRABEC a José RUIZ. A Novel Benzothiazole-1,2,3-Triazole-Based Arene Osmium(II) Complex as an Effective Rhabdomyosarcoma Cancer Stem Cell Agent. Inorganic Chemistry Frontiers. Royal Society of Chemistry, 2025, roč. 12, č. 4, s. 1693-1715. ISSN 2052-1553. Dostupné z: https://dx.doi.org/10.1039/D4QI02737J.

@article{2481400,
   author = {Sharkawy, Sofia and HernándezandGarcía, Alba and Kostrhunová, Hana and Bautista, Delia and Marková, Lenka and Santana, María Dolores and Kašpárková, Jana and Brabec, Viktor and Ruiz, José},
   article_number = {4},
   doi = {http://dx.doi.org/10.1039/D4QI02737J},
   keywords = {BOVINE SERUM-ALBUMIN; BINDING; RUTHENIUM(II); ANTITUMOR; INHIBITION; WARFARIN; LIGANDS; ANALOGS; GROWTH},
   language = {eng},
   issn = {2052-1553},
   journal = {Inorganic Chemistry Frontiers},
   title = {A Novel Benzothiazole-1,2,3-Triazole-Based Arene Osmium(II) Complex as an Effective Rhabdomyosarcoma Cancer Stem Cell Agent},
   url = {https://doi.org/10.1039/D4QI02737J},
   volume = {12},
   year = {2025}
}

TY  - JOUR
ID  - 2481400
AU  - Sharkawy, Sofia - Hernández-García, Alba - Kostrhunová, Hana - Bautista, Delia - Marková, Lenka - Santana, María Dolores - Kašpárková, Jana - Brabec, Viktor - Ruiz, José
PY  - 2025
TI  - A Novel Benzothiazole-1,2,3-Triazole-Based Arene Osmium(II) Complex as an Effective Rhabdomyosarcoma Cancer Stem Cell Agent
JF  - Inorganic Chemistry Frontiers
VL  - 12
IS  - 4
SP  - 1693-1715
EP  - 1693-1715
PB  - Royal Society of Chemistry
SN  - 20521553
KW  - BOVINE SERUM-ALBUMIN
KW  - BINDING
KW  - RUTHENIUM(II)
KW  - ANTITUMOR
KW  - INHIBITION
KW  - WARFARIN
KW  - LIGANDS
KW  - ANALOGS
KW  - GROWTH
UR  - https://doi.org/10.1039/D4QI02737J
N2  - We designed a series of pseudo-octahedral arene Os(II) complexes (Os1–Os5) with the general formula [(η6-p-cym)Os(BTAT)Cl]+, where BTAT represents chelating N^N′ ligands based on the 1-aryl-4-benzothiazolyl-1,2,3-triazole scaffold. The structures of Os3 and Os5 were confirmed by X-ray diffraction, and Os5 exhibits a bathochromic shift in its absorption band compared to the other complexes, likely due to the electron-donating properties of the substituent NMe2. Os5 also hydrolyzed without losing its BTAT ligand and exhibited the highest cellular accumulation in Rhabdomyosarcoma (RD) cancer cells. The investigated Os(II) complexes demonstrated moderate antiproliferative activity across six cancer cell lines, with Os5 being the most potent, showing activity comparable to or better than conventional cisplatin. Cellular accumulation was a key factor influencing their antiproliferative effect, though binding to human serum albumin did not play a significant role. Further studies with Os5 in RD cells, the most responsive cell line, revealed that its mechanism of action includes mitochondrial dysfunction, apoptosis via a caspase-dependent pathway, and cell cycle arrest at the G1 phase. Os5 also increased the production/generation of reactive oxygen species (ROS) in RD cells, implicating ROS production as a contributor to its activity. Importantly, Os5 was effective against cancer stem cells (CSCs) in 3D spheroid models, marking the first report of an osmium-based compound targeting CSC-enriched RD cells. This highlights the potential of Os5 as a CSC-targeted therapy, addressing the need for treatments that prevent relapse and metastasis. The study underscores the promising role of metal-based complexes in cancer stem cell chemotherapy.
ER  -

SHARKAWY, Sofia; Alba HERNÁNDEZ-GARCÍA; Hana KOSTRHUNOVÁ; Delia BAUTISTA; Lenka MARKOVÁ; María Dolores SANTANA; Jana KAŠPÁRKOVÁ; Viktor BRABEC a José RUIZ. A Novel Benzothiazole-1,2,3-Triazole-Based Arene Osmium(II) Complex as an Effective Rhabdomyosarcoma Cancer Stem Cell Agent. \textit{Inorganic Chemistry Frontiers}. Royal Society of Chemistry, 2025, roč.~12, č.~4, s.~1693-1715. ISSN~2052-1553. Dostupné z: https://dx.doi.org/10.1039/D4QI02737J.

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