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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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Bioinorganic Chemistry and Applications |
| Online Access: | http://dx.doi.org/10.1155/2022/1717200 |
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| author | Jana Kasparkova Hana Kostrhunova Vojtech Novohradsky Аlexey A. Logvinov Viktor V. Temnov Nataliya E. Borisova Tatiana A. Podrugina Lenka Markova Pavel Starha Alexey. A. Nazarov Viktor Brabec |
| author_facet | Jana Kasparkova Hana Kostrhunova Vojtech Novohradsky Аlexey A. Logvinov Viktor V. Temnov Nataliya E. Borisova Tatiana A. Podrugina Lenka Markova Pavel Starha Alexey. A. Nazarov Viktor Brabec |
| author_sort | Jana Kasparkova |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-3ca46adcbf094b3faac19d8bb49e9a33 |
| institution | Kabale University |
| issn | 1687-479X |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Bioinorganic Chemistry and Applications |
| spelling | doaj-art-3ca46adcbf094b3faac19d8bb49e9a332025-02-03T06:13:38ZengWileyBioinorganic Chemistry and Applications1687-479X2022-01-01202210.1155/2022/1717200Novel cis-Pt(II) Complexes with Alkylpyrazole Ligands: Synthesis, Characterization, and Unusual Mode of Anticancer ActionJana Kasparkova0Hana Kostrhunova1Vojtech Novohradsky2Аlexey A. Logvinov3Viktor V. Temnov4Nataliya E. Borisova5Tatiana A. Podrugina6Lenka Markova7Pavel Starha8Alexey. A. Nazarov9Viktor Brabec10Czech Academy of SciencesCzech Academy of SciencesCzech Academy of SciencesLomonosov Moscow State UniversityLomonosov Moscow State UniversityLomonosov Moscow State UniversityLomonosov Moscow State UniversityCzech Academy of SciencesCzech Academy of SciencesLomonosov Moscow State UniversityCzech Academy of SciencesOne 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.http://dx.doi.org/10.1155/2022/1717200 |
| spellingShingle | Jana Kasparkova Hana Kostrhunova Vojtech Novohradsky Аlexey A. Logvinov Viktor V. Temnov Nataliya E. Borisova Tatiana A. Podrugina Lenka Markova Pavel Starha Alexey. A. Nazarov Viktor Brabec Novel cis-Pt(II) Complexes with Alkylpyrazole Ligands: Synthesis, Characterization, and Unusual Mode of Anticancer Action Bioinorganic Chemistry and Applications |
| 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 |
| url | http://dx.doi.org/10.1155/2022/1717200 |
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