2. Academic Validation
  3. Design, synthesis and anticancer properties of IsoCombretaQuinolines as potent tubulin assembly inhibitors

Design, synthesis and anticancer properties of IsoCombretaQuinolines as potent tubulin assembly inhibitors

  • Eur J Med Chem. 2017 Feb 15:127:1025-1034. doi: 10.1016/j.ejmech.2016.11.012.
Ilhem Khelifi 1,  Timothée Naret 1,  Dolor Renko 1,  Abdallah Hamze 1,  Guillaume Bernadat 1,  Jérome Bignon 2,  Christine Lenoir 2,  Joëlle Dubois 2,  Jean-Daniel Brion 1,  Olivier Provot 3,  Mouad Alami 4
Affiliations

Affiliations

  • 1 BioCIS, Univ. Paris-Sud, CNRS, Université Paris-Saclay, 92290, Châtenay-Malabry, France.
  • 2 Institut de Chimie des Substances Naturelles, UPR 2301, CNRS Avenue de La Terrasse, F-91198 Gif sur Yvette, France.
  • 3 BioCIS, Univ. Paris-Sud, CNRS, Université Paris-Saclay, 92290, Châtenay-Malabry, France. Electronic address: olivier.provot@u-psud.fr.
  • 4 BioCIS, Univ. Paris-Sud, CNRS, Université Paris-Saclay, 92290, Châtenay-Malabry, France. Electronic address: mouad.alami@u-psud.fr.
PMID: 28166995 DOI: 10.1016/j.ejmech.2016.11.012
Abstract

The synthesis and evaluation of a new series of IsoCombretaQuinolines (IsoCoQuines) 2 with a 2-substituted-quinoline in place of the 3,4,5-trimethoxyphenyl ring present in isoCA-4 and CA-4 are described. Most of these compounds displayed a potent cytotoxic activity (IC50 < 10 nM) against a panel of five human Cancer cell lines and inhibited tubulin assembly at a micromolar level. The most potent analogue 2b, having a 3-hydroxy-4-methoxyphenyl as B-ring, led to cell cycle arrest in G2/M phase. Docking studies indicate that 2b showed a binding mode comparable to those previously observed with quinazoline analogous (IsoCoQ) and with isoCA-4 at the colchicine binding site of tubulin.

Keywords

Binding; Cancer; Cytotoxicity; Quinoline; Tubulin; isoCA-4.

Figures