A Novel Benzothiazole-1,2,3-Triazole-Based Arene Osmium(II) Complex as an Effective Rhabdomyosarcoma Cancer Stem Cell Agent
The result's identifiers
Result code in 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>
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
A Novel Benzothiazole-1,2,3-Triazole-Based Arene Osmium(II) Complex as an Effective Rhabdomyosarcoma Cancer Stem Cell Agent
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
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Continuities
S - Specificky vyzkum na vysokych skolach
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Inorganic Chemistry Frontiers
ISSN
2052-1553
e-ISSN
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Volume of the periodical
12
Issue of the periodical within the volume
4
Country of publishing house
GB - UNITED KINGDOM
Number of pages
23
Pages from-to
1693-1715
UT code for WoS article
001397563900001
EID of the result in the Scopus database
2-s2.0-85215704168