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
  • 1. Université Paris-Saclay, CNRS, BioCIS, 92290, Châtenay-Malabry, France.
  • 2. Université Paris-Saclay, CNRS, BioCIS, 92290, Châtenay-Malabry, France. Electronic address: [email protected].
  • 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: [email protected].
  • 9. Université Paris-Saclay, CNRS, BioCIS, 92290, Châtenay-Malabry, France. Electronic address: [email protected].
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.