Inhibition of microtubule dynamics in cancer cells by indole-modified latonduine derivatives and their metal complexes Journal Article
| Authors: | Wittmann, C.; Sivchenko, A. S.; Bacher, F.; Tong, K. K. H.; Guru, N.; Wilson, T.; Gonzales, J.; Rauch, H.; Kossatz, S.; Reiner, T.; Babak, M. V.; Arion, V. B. |
| Article Title: | Inhibition of microtubule dynamics in cancer cells by indole-modified latonduine derivatives and their metal complexes |
| Abstract: | Indolo[2,3-d]benzazepines (indololatonduines) are rarely discussed in the literature. In this project, we prepared a series of novel indololatonduine derivatives and their RuII and OsII complexes and investigated their microtubule-targeting properties in comparison with paclitaxel and colchicine. Compounds were fully characterized by spectroscopic techniques (1H NMR and UV-vis), ESI mass-spectrometry, and X-ray crystallography, and their purity was confirmed by elemental analysis. The stabilities of the compounds in DMSO and water were confirmed by 1H and 13C NMR and UV-vis spectroscopy. Novel indololatonduines demonstrated anticancer activity in vitro in a low micromolar concentration range, while their coordination to metal centers resulted in a decrease of cytotoxicity. The preliminary in vivo activity of the RuII complex was investigated. Fluorescence staining and in vitro tubulin polymerization assays revealed the prepared compounds to have excellent microtubule-destabilizing activities, even more potent than the well-known microtubule-destabilizing agent colchicine. © 2022 The Authors. Published by American Chemical Society. |
| Keywords: | antineoplastic agents; paclitaxel; antineoplastic agent; mass spectrometry; mouse; animal; metabolism; animals; mice; cell survival; drug effect; drug screening; pathology; tumor cell culture; drug screening assays, antitumor; tumor cells, cultured; chemistry; nude mouse; mice, nude; polymerization; fluorescence microscopy; microscopy, fluorescence; models, molecular; crystallography, x-ray; chemical structure; molecular structure; indoles; x ray crystallography; fused heterocyclic rings; in-vitro; tubulin; microtubule; microtubules; indole derivative; synthesis; molecular model; cancer cells; mammary neoplasms, experimental; ruthenium compounds; coordination compound; coordination complexes; microtubule dynamics; property; spectroscopic analysis; indole; ultraviolet visible spectroscopy; metal complexes; heterocyclic compounds, 3-ring; humans; human; 1h nmr; osmium compounds; 1h and 13c nmr; esi mass spectrometry; spectroscopic technique; latonduine a; latonduine b; experimental mammary neoplasm |
| Journal Title: | Inorganic Chemistry |
| Volume: | 61 |
| Issue: | 3 |
| ISSN: | 0020-1669 |
| Publisher: | ACS Publications |
| Date Published: | 2022-01-24 |
| Start Page: | 1456 |
| End Page: | 1470 |
| Language: | English |
| DOI: | 10.1021/acs.inorgchem.1c03154 |
| PUBMED: | 34995063 |
| PROVIDER: | scopus |
| PMCID: | PMC8790753 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 March 2022 -- Source: Scopus |
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