Synthesis and Antiparasitic Activity of New Trithiolato-Bridged Dinuclear Ruthenium(II)-arene-carbohydrate Conjugates
Eight novel carbohydrate-tethered trithiolato dinuclear ruthenium(II)-arene complexes were synthesized using CuAAC ‘click’ (Cu(I)-catalyzed azide-alkyne cycloaddition) reactions, and there in vitro activity against transgenic <i>T. gondii</i> tachyzoites constitutively expressing β-galac...
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| Format: | Article |
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MDPI AG
2023-01-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/2/902 |
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| author | Isabelle Holzer Oksana Desiatkina Nicoleta Anghel Serena K. Johns Ghalia Boubaker Andrew Hemphill Julien Furrer Emilia Păunescu |
| author_facet | Isabelle Holzer Oksana Desiatkina Nicoleta Anghel Serena K. Johns Ghalia Boubaker Andrew Hemphill Julien Furrer Emilia Păunescu |
| author_sort | Isabelle Holzer |
| collection | DOAJ |
| description | Eight novel carbohydrate-tethered trithiolato dinuclear ruthenium(II)-arene complexes were synthesized using CuAAC ‘click’ (Cu(I)-catalyzed azide-alkyne cycloaddition) reactions, and there in vitro activity against transgenic <i>T. gondii</i> tachyzoites constitutively expressing β-galactosidase (<i>T. gondii</i> β-gal) and in non-infected human foreskin fibroblasts, HFF, was determined at 0.1 and 1 µM. When evaluated at 1 µM, seven diruthenium-carbohydrate conjugates strongly impaired parasite proliferation by >90%, while HFF viability was retained at 50% or more, and they were further subjected to the half-maximal inhibitory concentration (IC<sub>50</sub>) measurement on <i>T. gondii</i> β-gal. Results revealed that the biological activity of the hybrids was influenced both by the nature of the carbohydrate (glucose vs. galactose) appended on ruthenium complex and the type/length of the linker between the two units. <b>23</b> and <b>26</b>, two galactose-based diruthenium conjugates, exhibited low IC<sub>50</sub> values and reduced effect on HFF viability when applied at 2.5 µM (<b>23</b>: IC<sub>50</sub> = 0.032 µM/HFF viability 92% and <b>26</b>: IC<sub>50</sub> = 0.153 µM/HFF viability 97%). Remarkably, compounds <b>23</b> and <b>26</b> performed significantly better than the corresponding carbohydrate non-modified diruthenium complexes, showing that this type of conjugates are a promising approach for obtaining new antiparasitic compounds with reduced toxicity. |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T11:33:44Z |
| publishDate | 2023-01-01 |
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| record_format | Article |
| series | Molecules |
| spelling | doaj.art-9c27ac6421184771a266cf12b34507552023-11-30T23:46:35ZengMDPI AGMolecules1420-30492023-01-0128290210.3390/molecules28020902Synthesis and Antiparasitic Activity of New Trithiolato-Bridged Dinuclear Ruthenium(II)-arene-carbohydrate ConjugatesIsabelle Holzer0Oksana Desiatkina1Nicoleta Anghel2Serena K. Johns3Ghalia Boubaker4Andrew Hemphill5Julien Furrer6Emilia Păunescu7Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, 3012 Bern, SwitzerlandDepartment of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, 3012 Bern, SwitzerlandInstitute of Parasitology Vetsuisse Faculty, University of Bern, Länggass-Strasse 122, 3012 Bern, SwitzerlandDepartment of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, 3012 Bern, SwitzerlandInstitute of Parasitology Vetsuisse Faculty, University of Bern, Länggass-Strasse 122, 3012 Bern, SwitzerlandInstitute of Parasitology Vetsuisse Faculty, University of Bern, Länggass-Strasse 122, 3012 Bern, SwitzerlandDepartment of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, 3012 Bern, SwitzerlandDepartment of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, 3012 Bern, SwitzerlandEight novel carbohydrate-tethered trithiolato dinuclear ruthenium(II)-arene complexes were synthesized using CuAAC ‘click’ (Cu(I)-catalyzed azide-alkyne cycloaddition) reactions, and there in vitro activity against transgenic <i>T. gondii</i> tachyzoites constitutively expressing β-galactosidase (<i>T. gondii</i> β-gal) and in non-infected human foreskin fibroblasts, HFF, was determined at 0.1 and 1 µM. When evaluated at 1 µM, seven diruthenium-carbohydrate conjugates strongly impaired parasite proliferation by >90%, while HFF viability was retained at 50% or more, and they were further subjected to the half-maximal inhibitory concentration (IC<sub>50</sub>) measurement on <i>T. gondii</i> β-gal. Results revealed that the biological activity of the hybrids was influenced both by the nature of the carbohydrate (glucose vs. galactose) appended on ruthenium complex and the type/length of the linker between the two units. <b>23</b> and <b>26</b>, two galactose-based diruthenium conjugates, exhibited low IC<sub>50</sub> values and reduced effect on HFF viability when applied at 2.5 µM (<b>23</b>: IC<sub>50</sub> = 0.032 µM/HFF viability 92% and <b>26</b>: IC<sub>50</sub> = 0.153 µM/HFF viability 97%). Remarkably, compounds <b>23</b> and <b>26</b> performed significantly better than the corresponding carbohydrate non-modified diruthenium complexes, showing that this type of conjugates are a promising approach for obtaining new antiparasitic compounds with reduced toxicity.https://www.mdpi.com/1420-3049/28/2/902ruthenium(II)-arene complexesbioorganometalliccarbohydratesCuAAC reactionsantiparasitic<i>Toxoplasma gondii</i> |
| spellingShingle | Isabelle Holzer Oksana Desiatkina Nicoleta Anghel Serena K. Johns Ghalia Boubaker Andrew Hemphill Julien Furrer Emilia Păunescu Synthesis and Antiparasitic Activity of New Trithiolato-Bridged Dinuclear Ruthenium(II)-arene-carbohydrate Conjugates Molecules ruthenium(II)-arene complexes bioorganometallic carbohydrates CuAAC reactions antiparasitic <i>Toxoplasma gondii</i> |
| title | Synthesis and Antiparasitic Activity of New Trithiolato-Bridged Dinuclear Ruthenium(II)-arene-carbohydrate Conjugates |
| title_full | Synthesis and Antiparasitic Activity of New Trithiolato-Bridged Dinuclear Ruthenium(II)-arene-carbohydrate Conjugates |
| title_fullStr | Synthesis and Antiparasitic Activity of New Trithiolato-Bridged Dinuclear Ruthenium(II)-arene-carbohydrate Conjugates |
| title_full_unstemmed | Synthesis and Antiparasitic Activity of New Trithiolato-Bridged Dinuclear Ruthenium(II)-arene-carbohydrate Conjugates |
| title_short | Synthesis and Antiparasitic Activity of New Trithiolato-Bridged Dinuclear Ruthenium(II)-arene-carbohydrate Conjugates |
| title_sort | synthesis and antiparasitic activity of new trithiolato bridged dinuclear ruthenium ii arene carbohydrate conjugates |
| topic | ruthenium(II)-arene complexes bioorganometallic carbohydrates CuAAC reactions antiparasitic <i>Toxoplasma gondii</i> |
| url | https://www.mdpi.com/1420-3049/28/2/902 |
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