2. Academic Validation
  3. Anticancer properties of indole derivatives as IsoCombretastatin A-4 analogues

Anticancer properties of indole derivatives as IsoCombretastatin A-4 analogues

  • Eur J Med Chem. 2021 Nov 5:223:113656. doi: 10.1016/j.ejmech.2021.113656.
Shannon Pecnard 1,  Abdallah Hamze 2,  Jérome Bignon 3,  Bastien Prost 4,  Alain Deroussent 5,  Laura Gallego-Yerga 6,  Rafael Peláez 6,  Ji Yeon Paik 7,  Marc Diederich 7,  Mouad Alami 8,  Olivier Provot 9
Affiliations

Affiliations

  • 1 Université Paris-Saclay, CNRS, BioCIS, 92290, Châtenay-Malabry, France.
  • 2 Université Paris-Saclay, CNRS, BioCIS, 92290, Châtenay-Malabry, France. Electronic address: abdallah.hamze@universite-paris-saclay.fr.
  • 3 Institut de Chimie des Substances Naturelles, UPR 2301, CNRS Avenue de La Terrasse, F-91198, Gif sur Yvette, France.
  • 4 Service D'Analyse des Médicaments et Métabolites, IPSIT, Univ. Paris-Sud, UMS 3679 CNRS, US 31 INSERM, Université Paris-Saclay, 92290, Châtenay Malabry, France.
  • 5 Metabolic and Systemic Aspects of Oncogenesis (METSY), UMR 9018, CNRS, Institut Gustave Roussy, Université Paris-Saclay, 94805, Villejuif, France.
  • 6 Laboratorio de Química Orgánica y Farmacéutica, Departamento de Ciencias Farmacéuticas, Facultad de Farmacia, Universidad de Salamanca, Salamanca, Spain.
  • 7 Department of Pharmacy, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08626, South Korea.
  • 8 Université Paris-Saclay, CNRS, BioCIS, 92290, Châtenay-Malabry, France. Electronic address: mouad.alami@universite-paris-saclay.fr.
  • 9 Université Paris-Saclay, CNRS, BioCIS, 92290, Châtenay-Malabry, France. Electronic address: olivier.provot@universite-paris-saclay.fr.
PMID: 34171660 DOI: 10.1016/j.ejmech.2021.113656
Abstract

In this study, a variety of original ligands related to Combretastatin A-4 and isoCombretastatin A-4, able to inhibit the tubulin polymerization into microtubules, was designed, synthesized, and evaluated. Our lead compound 15d having a quinazoline as A-ring and a 2-substituted indole as B-ring separated by a N-methyl linker displayed a remarkable sub-nanomolar level of cytotoxicity (IC50 < 1 nM) against 9 human Cancer cell lines.

Keywords

Cancer; Cytotoxicity; Indole; Oxazinoindole; Pyridoindole; Quinazoline; Tubulin; isoCA-4.

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