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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F25%3A00140739" target="_blank" >RIV/00216224:14310/25:00140739 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1039/D4QI02737J" target="_blank" >https://doi.org/10.1039/D4QI02737J</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/D4QI02737J" target="_blank" >10.1039/D4QI02737J</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

—

Návaznosti

S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Inorganic Chemistry Frontiers

ISSN

2052-1553

e-ISSN

—

Svazek periodika

12

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

23

Strana od-do

1693-1715

Kód UT WoS článku

001397563900001

EID výsledku v databázi Scopus

2-s2.0-85215704168