Synthesis and Biological Activity of Ferrocenyl and Ruthenocenyl Analogues of Etoposide: Discovery of a Novel Dual Inhibitor of Topoisomerase II Activity and Tubulin Polymerization
| Autor: | Błażej Rychlik, Marcin Wachulec, Martyna Gruchała, Karolina Chrabąszcz, Damian Plażuk, Andrzej Błauż |
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| Rok vydání: | 2020 |
| Předmět: |
Stereochemistry
Antineoplastic Agents 010402 general chemistry 01 natural sciences Catalysis Polymerization Structure-Activity Relationship Tubulin Cell Line Tumor medicine Topoisomerase II Inhibitors Cytotoxicity Etoposide Cell Proliferation biology 010405 organic chemistry Chemistry Topoisomerase Organic Chemistry Biological activity General Chemistry Cell cycle 0104 chemical sciences DNA Topoisomerases Type II biology.protein Topoisomerase-II Inhibitor Drug Screening Assays Antitumor Linker medicine.drug Conjugate |
| Zdroj: | Chemistry (Weinheim an der Bergstrasse, Germany). 27(20) |
| ISSN: | 1521-3765 |
| Popis: | Two series of the ferrocenyl and ruthenocenyl analogues of etoposide bearing 1,2,3-triazolyl or aminoalkyl linker were synthesized and evaluated for their cytotoxic properties, influence on the cell cycle, ability to induce tubulin polymerization, and inhibition of topoisomerase II activity. We found that the replacement of the etoposide carbohydrate moiety with a metallocenyl group led to organometallic conjugates exhibiting differentiated antiproliferative activity. Biological studies demonstrated that two ferrocenylalkylamino conjugates were notably more active than etoposide, with submicromolar or low-micromolar IC50 values towards SW620, etoposide-resistant SW620E, and methotrexate-resistant SW620M cancer cell lines. Moreover, the simplest ferrocenylmethylamino conjugate exerted dual inhibitory action against tubulin polymerization and topoisomerase II activity while other studied compounds affected only topoisomerase II activity. |
| Databáze: | OpenAIRE |
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