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Novel cis-Pt(II) Complexes with Alkylpyrazole Ligands: Synthesis, Characterization, and Unusual Mode of Anticancer Action

One concept of improving anticancer effects of conventional platinum-based antitumor drugs consists of conjugating these compounds with other biologically (antitumor) active agents, acting by a different mechanism. Here, we present synthesis, physicochemical characterization, biological effects, and...

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Autores principales: Kasparkova, Jana, Kostrhunova, Hana, Novohradsky, Vojtech, Logvinov, Аlexey A., Temnov, Viktor V., Borisova, Nataliya E., Podrugina, Tatiana A., Markova, Lenka, Starha, Pavel, Nazarov, Alexey. A., Brabec, Viktor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8906972/
https://www.ncbi.nlm.nih.gov/pubmed/35281329
http://dx.doi.org/10.1155/2022/1717200
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author Kasparkova, Jana
Kostrhunova, Hana
Novohradsky, Vojtech
Logvinov, Аlexey A.
Temnov, Viktor V.
Borisova, Nataliya E.
Podrugina, Tatiana A.
Markova, Lenka
Starha, Pavel
Nazarov, Alexey. A.
Brabec, Viktor
author_facet Kasparkova, Jana
Kostrhunova, Hana
Novohradsky, Vojtech
Logvinov, Аlexey A.
Temnov, Viktor V.
Borisova, Nataliya E.
Podrugina, Tatiana A.
Markova, Lenka
Starha, Pavel
Nazarov, Alexey. A.
Brabec, Viktor
author_sort Kasparkova, Jana
collection PubMed
description One concept of improving anticancer effects of conventional platinum-based antitumor drugs consists of conjugating these compounds with other biologically (antitumor) active agents, acting by a different mechanism. Here, we present synthesis, physicochemical characterization, biological effects, and mechanisms of action of four new analogs of conventional cisplatin, namely, cis-Pt(II) complexes containing either methyl or ethyl pyrazole N-donor ligands and chlorido or iodido ligands. It is noteworthy that while chlorido complexes display activity in a variety of cancer cell lines comparable to cisplatin, iodido complexes are considerably more potent due to their enhanced hydrophobicity and consequently enhanced cellular accumulation. Moreover, all of the studied Pt(II) alkylpyrazole complexes display a higher selectivity for tumor cells and effectively overcome the acquired resistance to cisplatin. Further results focused on the mechanism of action of the studied complexes and showed that in contrast to cisplatin and several platinum-based antitumor drugs, DNA damage by the investigated Pt(II)-alkylpyrazole complexes does not play a major role in their mechanism of action. Our findings demonstrate that inhibition of the tubulin kinesin Eg5, which is essential for forming a functional mitotic spindle, plays an important role in their mechanism of antiproliferative action.
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spelling pubmed-89069722022-03-10 Novel cis-Pt(II) Complexes with Alkylpyrazole Ligands: Synthesis, Characterization, and Unusual Mode of Anticancer Action Kasparkova, Jana Kostrhunova, Hana Novohradsky, Vojtech Logvinov, Аlexey A. Temnov, Viktor V. Borisova, Nataliya E. Podrugina, Tatiana A. Markova, Lenka Starha, Pavel Nazarov, Alexey. A. Brabec, Viktor Bioinorg Chem Appl Research Article One concept of improving anticancer effects of conventional platinum-based antitumor drugs consists of conjugating these compounds with other biologically (antitumor) active agents, acting by a different mechanism. Here, we present synthesis, physicochemical characterization, biological effects, and mechanisms of action of four new analogs of conventional cisplatin, namely, cis-Pt(II) complexes containing either methyl or ethyl pyrazole N-donor ligands and chlorido or iodido ligands. It is noteworthy that while chlorido complexes display activity in a variety of cancer cell lines comparable to cisplatin, iodido complexes are considerably more potent due to their enhanced hydrophobicity and consequently enhanced cellular accumulation. Moreover, all of the studied Pt(II) alkylpyrazole complexes display a higher selectivity for tumor cells and effectively overcome the acquired resistance to cisplatin. Further results focused on the mechanism of action of the studied complexes and showed that in contrast to cisplatin and several platinum-based antitumor drugs, DNA damage by the investigated Pt(II)-alkylpyrazole complexes does not play a major role in their mechanism of action. Our findings demonstrate that inhibition of the tubulin kinesin Eg5, which is essential for forming a functional mitotic spindle, plays an important role in their mechanism of antiproliferative action. Hindawi 2022-03-02 /pmc/articles/PMC8906972/ /pubmed/35281329 http://dx.doi.org/10.1155/2022/1717200 Text en Copyright © 2022 Jana Kasparkova et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Kasparkova, Jana
Kostrhunova, Hana
Novohradsky, Vojtech
Logvinov, Аlexey A.
Temnov, Viktor V.
Borisova, Nataliya E.
Podrugina, Tatiana A.
Markova, Lenka
Starha, Pavel
Nazarov, Alexey. A.
Brabec, Viktor
Novel cis-Pt(II) Complexes with Alkylpyrazole Ligands: Synthesis, Characterization, and Unusual Mode of Anticancer Action
title Novel cis-Pt(II) Complexes with Alkylpyrazole Ligands: Synthesis, Characterization, and Unusual Mode of Anticancer Action
title_full Novel cis-Pt(II) Complexes with Alkylpyrazole Ligands: Synthesis, Characterization, and Unusual Mode of Anticancer Action
title_fullStr Novel cis-Pt(II) Complexes with Alkylpyrazole Ligands: Synthesis, Characterization, and Unusual Mode of Anticancer Action
title_full_unstemmed Novel cis-Pt(II) Complexes with Alkylpyrazole Ligands: Synthesis, Characterization, and Unusual Mode of Anticancer Action
title_short Novel cis-Pt(II) Complexes with Alkylpyrazole Ligands: Synthesis, Characterization, and Unusual Mode of Anticancer Action
title_sort novel cis-pt(ii) complexes with alkylpyrazole ligands: synthesis, characterization, and unusual mode of anticancer action
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8906972/
https://www.ncbi.nlm.nih.gov/pubmed/35281329
http://dx.doi.org/10.1155/2022/1717200
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