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. Epub 2021 Jun 18.

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.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Binding Sites
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Resistance, Neoplasm / drug effects
  • Drug Screening Assays, Antitumor
  • Drug Stability
  • Humans
  • Indoles / chemistry*
  • Indoles / metabolism
  • Indoles / pharmacology
  • Microsomes, Liver / metabolism
  • Molecular Docking Simulation
  • Rats
  • Stilbenes / chemistry*
  • Stilbenes / metabolism
  • Stilbenes / pharmacology
  • Structure-Activity Relationship
  • Tubulin / chemistry
  • Tubulin / metabolism
  • Tubulin Modulators / chemistry*
  • Tubulin Modulators / metabolism
  • Tubulin Modulators / pharmacology

Substances

  • Antineoplastic Agents
  • Indoles
  • Stilbenes
  • Tubulin
  • Tubulin Modulators
  • fosbretabulin