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

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

2 Scopus Citations
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Author(s)

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

Related Research Unit(s)

Detail(s)

Original languageEnglish
Pages (from-to)1456–1470
Journal / PublicationInorganic Chemistry
Volume61
Issue number3
Online published7 Jan 2022
Publication statusPublished - 24 Jan 2022

Link(s)

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.

Research Area(s)

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

Citation Format(s)

Inhibition of Microtubule Dynamics in Cancer Cells by Indole-Modified Latonduine Derivatives and Their Metal Complexes. / Wittmann, Christopher; Sivchenko, Anastasiia S.; Bacher, Felix; Tong, Kelvin K. H.; Guru, Navjot; Wilson, Thomas; Gonzales, Junior; Rauch, Hartmut; Kossatz, Susanne; Reiner, Thomas; Babak, Maria V.; Arion, Vladimir B.

In: Inorganic Chemistry, Vol. 61, No. 3, 24.01.2022, p. 1456–1470.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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