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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 T. gondii tachyzoites constitutively expressing β-galactosidase (T. gondii...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9865825/ https://www.ncbi.nlm.nih.gov/pubmed/36677958 http://dx.doi.org/10.3390/molecules28020902 |
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author | Holzer, Isabelle Desiatkina, Oksana Anghel, Nicoleta Johns, Serena K. Boubaker, Ghalia Hemphill, Andrew Furrer, Julien Păunescu, Emilia |
author_facet | Holzer, Isabelle Desiatkina, Oksana Anghel, Nicoleta Johns, Serena K. Boubaker, Ghalia Hemphill, Andrew Furrer, Julien Păunescu, Emilia |
author_sort | Holzer, Isabelle |
collection | PubMed |
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 T. gondii tachyzoites constitutively expressing β-galactosidase (T. gondii 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(50)) measurement on T. gondii 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. 23 and 26, two galactose-based diruthenium conjugates, exhibited low IC(50) values and reduced effect on HFF viability when applied at 2.5 µM (23: IC(50) = 0.032 µM/HFF viability 92% and 26: IC(50) = 0.153 µM/HFF viability 97%). Remarkably, compounds 23 and 26 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. |
format | Online Article Text |
id | pubmed-9865825 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98658252023-01-22 Synthesis and Antiparasitic Activity of New Trithiolato-Bridged Dinuclear Ruthenium(II)-arene-carbohydrate Conjugates Holzer, Isabelle Desiatkina, Oksana Anghel, Nicoleta Johns, Serena K. Boubaker, Ghalia Hemphill, Andrew Furrer, Julien Păunescu, Emilia Molecules Article 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 T. gondii tachyzoites constitutively expressing β-galactosidase (T. gondii 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(50)) measurement on T. gondii 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. 23 and 26, two galactose-based diruthenium conjugates, exhibited low IC(50) values and reduced effect on HFF viability when applied at 2.5 µM (23: IC(50) = 0.032 µM/HFF viability 92% and 26: IC(50) = 0.153 µM/HFF viability 97%). Remarkably, compounds 23 and 26 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. MDPI 2023-01-16 /pmc/articles/PMC9865825/ /pubmed/36677958 http://dx.doi.org/10.3390/molecules28020902 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Holzer, Isabelle Desiatkina, Oksana Anghel, Nicoleta Johns, Serena K. Boubaker, Ghalia Hemphill, Andrew Furrer, Julien Păunescu, Emilia Synthesis and Antiparasitic Activity of New Trithiolato-Bridged Dinuclear Ruthenium(II)-arene-carbohydrate Conjugates |
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 | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9865825/ https://www.ncbi.nlm.nih.gov/pubmed/36677958 http://dx.doi.org/10.3390/molecules28020902 |
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