Investigations on the Anticancer Potential of Benzothiazole-Based Metallacycles
A series of 2-phenylbenzothiazole derivatives and their corresponding organometallic ruthenium(II) and osmium(II) complexes were synthesized, designed to exploit both, the attributes of the half-sandwich transition metal scaffold and the bioactivity spectrum of the applied 2-phenylbenzothiazoles. Al...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-04-01
|
| Series: | Frontiers in Chemistry |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fchem.2020.00209/full |
| _version_ | 1818064410657161216 |
|---|---|
| author | Stephan Mokesch Klaudia Cseh Heiko Geisler Michaela Hejl Matthias H. M. Klose Alexander Roller Samuel M. Meier-Menches Samuel M. Meier-Menches Michael A. Jakupec Michael A. Jakupec Wolfgang Kandioller Wolfgang Kandioller Bernhard K. Keppler Bernhard K. Keppler |
| author_facet | Stephan Mokesch Klaudia Cseh Heiko Geisler Michaela Hejl Matthias H. M. Klose Alexander Roller Samuel M. Meier-Menches Samuel M. Meier-Menches Michael A. Jakupec Michael A. Jakupec Wolfgang Kandioller Wolfgang Kandioller Bernhard K. Keppler Bernhard K. Keppler |
| author_sort | Stephan Mokesch |
| collection | DOAJ |
| description | A series of 2-phenylbenzothiazole derivatives and their corresponding organometallic ruthenium(II) and osmium(II) complexes were synthesized, designed to exploit both, the attributes of the half-sandwich transition metal scaffold and the bioactivity spectrum of the applied 2-phenylbenzothiazoles. All synthesized compounds were characterized via standard analytical methods. The obtained organometallics showed antiproliferative activity in the low μM range and are thus at least an order of magnitude more potent than the free ligands. ESI-MS measurements showed that the examined compounds were stable in aqueous solution over 48 h. Additionally, their binding preferences to small biomolecules, their cellular accumulation and capacity of inducing apoptosis/necrosis were investigated. Based on the fluorescence properties of the selected ligand and the corresponding ruthenium complex, their subcellular distribution was studied by fluorescence microscopy, revealing a high degree of colocalization with acidic organelles of cancer cells. |
| first_indexed | 2024-12-10T14:35:33Z |
| format | Article |
| id | doaj.art-68571d82c92d4b019aea10e20ae51176 |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-12-10T14:35:33Z |
| publishDate | 2020-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-68571d82c92d4b019aea10e20ae511762022-12-22T01:44:50ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462020-04-01810.3389/fchem.2020.00209530174Investigations on the Anticancer Potential of Benzothiazole-Based MetallacyclesStephan Mokesch0Klaudia Cseh1Heiko Geisler2Michaela Hejl3Matthias H. M. Klose4Alexander Roller5Samuel M. Meier-Menches6Samuel M. Meier-Menches7Michael A. Jakupec8Michael A. Jakupec9Wolfgang Kandioller10Wolfgang Kandioller11Bernhard K. Keppler12Bernhard K. Keppler13Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Vienna, AustriaInstitute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Vienna, AustriaInstitute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Vienna, AustriaInstitute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Vienna, AustriaInstitute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Vienna, AustriaInstitute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Vienna, AustriaResearch Cluster Translational Cancer Therapy Research, University of Vienna, Vienna, AustriaDepartment of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna, AustriaInstitute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Vienna, AustriaResearch Cluster Translational Cancer Therapy Research, University of Vienna, Vienna, AustriaInstitute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Vienna, AustriaResearch Cluster Translational Cancer Therapy Research, University of Vienna, Vienna, AustriaInstitute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Vienna, AustriaResearch Cluster Translational Cancer Therapy Research, University of Vienna, Vienna, AustriaA series of 2-phenylbenzothiazole derivatives and their corresponding organometallic ruthenium(II) and osmium(II) complexes were synthesized, designed to exploit both, the attributes of the half-sandwich transition metal scaffold and the bioactivity spectrum of the applied 2-phenylbenzothiazoles. All synthesized compounds were characterized via standard analytical methods. The obtained organometallics showed antiproliferative activity in the low μM range and are thus at least an order of magnitude more potent than the free ligands. ESI-MS measurements showed that the examined compounds were stable in aqueous solution over 48 h. Additionally, their binding preferences to small biomolecules, their cellular accumulation and capacity of inducing apoptosis/necrosis were investigated. Based on the fluorescence properties of the selected ligand and the corresponding ruthenium complex, their subcellular distribution was studied by fluorescence microscopy, revealing a high degree of colocalization with acidic organelles of cancer cells.https://www.frontiersin.org/article/10.3389/fchem.2020.00209/fullmetallacyclesanticancerbenzothiazolesruthenium complexesosmium complexes |
| spellingShingle | Stephan Mokesch Klaudia Cseh Heiko Geisler Michaela Hejl Matthias H. M. Klose Alexander Roller Samuel M. Meier-Menches Samuel M. Meier-Menches Michael A. Jakupec Michael A. Jakupec Wolfgang Kandioller Wolfgang Kandioller Bernhard K. Keppler Bernhard K. Keppler Investigations on the Anticancer Potential of Benzothiazole-Based Metallacycles Frontiers in Chemistry metallacycles anticancer benzothiazoles ruthenium complexes osmium complexes |
| title | Investigations on the Anticancer Potential of Benzothiazole-Based Metallacycles |
| title_full | Investigations on the Anticancer Potential of Benzothiazole-Based Metallacycles |
| title_fullStr | Investigations on the Anticancer Potential of Benzothiazole-Based Metallacycles |
| title_full_unstemmed | Investigations on the Anticancer Potential of Benzothiazole-Based Metallacycles |
| title_short | Investigations on the Anticancer Potential of Benzothiazole-Based Metallacycles |
| title_sort | investigations on the anticancer potential of benzothiazole based metallacycles |
| topic | metallacycles anticancer benzothiazoles ruthenium complexes osmium complexes |
| url | https://www.frontiersin.org/article/10.3389/fchem.2020.00209/full |
| work_keys_str_mv | AT stephanmokesch investigationsontheanticancerpotentialofbenzothiazolebasedmetallacycles AT klaudiacseh investigationsontheanticancerpotentialofbenzothiazolebasedmetallacycles AT heikogeisler investigationsontheanticancerpotentialofbenzothiazolebasedmetallacycles AT michaelahejl investigationsontheanticancerpotentialofbenzothiazolebasedmetallacycles AT matthiashmklose investigationsontheanticancerpotentialofbenzothiazolebasedmetallacycles AT alexanderroller investigationsontheanticancerpotentialofbenzothiazolebasedmetallacycles AT samuelmmeiermenches investigationsontheanticancerpotentialofbenzothiazolebasedmetallacycles AT samuelmmeiermenches investigationsontheanticancerpotentialofbenzothiazolebasedmetallacycles AT michaelajakupec investigationsontheanticancerpotentialofbenzothiazolebasedmetallacycles AT michaelajakupec investigationsontheanticancerpotentialofbenzothiazolebasedmetallacycles AT wolfgangkandioller investigationsontheanticancerpotentialofbenzothiazolebasedmetallacycles AT wolfgangkandioller investigationsontheanticancerpotentialofbenzothiazolebasedmetallacycles AT bernhardkkeppler investigationsontheanticancerpotentialofbenzothiazolebasedmetallacycles AT bernhardkkeppler investigationsontheanticancerpotentialofbenzothiazolebasedmetallacycles |