2. Academic Validation
  3. Synthesis, antiproliferative activity and tubulin targeting effect of acridinone and dioxophenothiazine derivatives

Synthesis, antiproliferative activity and tubulin targeting effect of acridinone and dioxophenothiazine derivatives

  • Eur J Med Chem. 2013 Jan:59:39-47. doi: 10.1016/j.ejmech.2012.10.051.
Valérie Verones 1,  Nathalie Flouquet,  Marie Lecoeur,  Amelie Lemoine,  Amaury Farce,  Brigitte Baldeyrou,  Christine Mahieu,  Nicole Wattez,  Amélie Lansiaux,  Jean-François Goossens,  Pascal Berthelot,  Nicolas Lebegue
Affiliations

Affiliation

  • 1 Université Lille Nord de France, Faculté des Sciences Pharmaceutiques et Biologiques, Laboratoire de Chimie Thérapeutique, EA 4481, IFR 114, 3 rue du Professeur Laguesse, BP-83, F-59006 Lille, France.
PMID: 23202849 DOI: 10.1016/j.ejmech.2012.10.051
Abstract

The synthesis of new acridinone and dioxophenothiazine derivatives along with their tubulin polymerization inhibitory and antiproliferative activities is reported. The analysis of correlation for cytotoxic and antitubulin potential of tested compounds showed that 4-methoxyphenylethyl derivatives 18a and 19a were highly cytotoxic but were regarded to have no significant antitubulin activity. However, the introduction of a 3-hydroxy substituent leading to compounds 18e and 19e, strongly increased the antitubulin potential but was associated with a loss of the antiproliferative activity. Modeling studies, Topoisomerase inhibition assays and cell cycle analysis have been performed to better investigate the mechanism of action of such compounds.

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