Inhibition of Microtubule Dynamics in Cancer Cells by Indole-Modified Latonduine Derivatives and Their Metal Complexes

Christopher Wittmann; Anastasiia S. Sivchenko; Felix Bacher; Kelvin K. H. Tong; Navjot Guru; Thomas Wilson; Junior Gonzales; Hartmut Rauch; Susanne Kossatz; Thomas Reiner; Maria V. Babak; Vladimir B. Arion

doi:10.1021/acs.inorgchem.1c03154

Inhibition of Microtubule Dynamics in Cancer Cells by Indole-Modified Latonduine Derivatives and Their Metal Complexes

Christopher Wittmann, Anastasiia S. Sivchenko, Felix Bacher, Kelvin K. H. Tong, Navjot Guru, Thomas Wilson, Junior Gonzales, Hartmut Rauch, Susanne Kossatz, Thomas Reiner^*, Maria V. Babak^*, Vladimir B. Arion^*

^*Corresponding author for this work

Department of Chemistry

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

16 Citations (Scopus)

75 Downloads (CityUHK Scholars)

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 Ru^II and Os^II 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 Ru^II 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.

Original language	English
Pages (from-to)	1456–1470
Journal	Inorganic Chemistry
Volume	61
Issue number	3
Online published	7 Jan 2022
DOIs	https://doi.org/10.1021/acs.inorgchem.1c03154
Publication status	Published - 24 Jan 2022

Research Keywords

TUBULIN INHIBITORS
KINASE INHIBITORS
RESISTANCE
COLCHICINE
MORPHOLINE
ANALOGS
SOLUBILITY
RUTHENIUM
PAULLONES
THERAPY

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This full text is made available under CC-BY 4.0. https://creativecommons.org/licenses/by/4.0/

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1021/acs.inorgchem.1c03154

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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. (2022). Inhibition of Microtubule Dynamics in Cancer Cells by Indole-Modified Latonduine Derivatives and Their Metal Complexes. Inorganic Chemistry, 61(3), 1456–1470. https://doi.org/10.1021/acs.inorgchem.1c03154

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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.",

keywords = "TUBULIN INHIBITORS, KINASE INHIBITORS, RESISTANCE, COLCHICINE, MORPHOLINE, ANALOGS, SOLUBILITY, RUTHENIUM, PAULLONES, THERAPY",

author = "Christopher Wittmann and Sivchenko, {Anastasiia S.} and Felix Bacher and Tong, {Kelvin K. H.} and Navjot Guru and Thomas Wilson and Junior Gonzales and Hartmut Rauch and Susanne Kossatz and Thomas Reiner and Babak, {Maria V.} and Arion, {Vladimir B.}",

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doi = "10.1021/acs.inorgchem.1c03154",

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Inhibition of Microtubule Dynamics in Cancer Cells by Indole-Modified Latonduine Derivatives and Their Metal Complexes. / Wittmann, Christopher; Sivchenko, Anastasiia S.; Bacher, Felix et al.
In: Inorganic Chemistry, Vol. 61, No. 3, 24.01.2022, p. 1456–1470.

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

TY - JOUR

T1 - Inhibition of Microtubule Dynamics in Cancer Cells by Indole-Modified Latonduine Derivatives and Their Metal Complexes

AU - Wittmann, Christopher

AU - Sivchenko, Anastasiia S.

AU - Bacher, Felix

AU - Tong, Kelvin K. H.

AU - Guru, Navjot

AU - Wilson, Thomas

AU - Gonzales, Junior

AU - Rauch, Hartmut

AU - Kossatz, Susanne

AU - Reiner, Thomas

AU - Babak, Maria V.

AU - Arion, Vladimir B.

PY - 2022/1/24

Y1 - 2022/1/24

N2 - 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.

AB - 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.

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KW - KINASE INHIBITORS

KW - RESISTANCE

KW - COLCHICINE

KW - MORPHOLINE

KW - ANALOGS

KW - SOLUBILITY

KW - RUTHENIUM

KW - PAULLONES

KW - THERAPY

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DO - 10.1021/acs.inorgchem.1c03154

M3 - RGC 21 - Publication in refereed journal

C2 - 34995063

SN - 0020-1669

VL - 61

SP - 1456

EP - 1470

JO - Inorganic Chemistry

JF - Inorganic Chemistry

IS - 3

ER -

Inhibition of Microtubule Dynamics in Cancer Cells by Indole-Modified Latonduine Derivatives and Their Metal Complexes

Abstract

Research Keywords

Publisher's Copyright Statement

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