New imidazoquinoxaline derivatives: Synthesis, biological evaluation on melanoma, effect on tubulin polymerization and structure-activity relationships

Bioorg Med Chem. 2016 Jun 1;24(11):2433-40. doi: 10.1016/j.bmc.2016.04.004. Epub 2016 Apr 1.


Microtubules are considered as important targets of anticancer therapy. EAPB0503 and its structural imidazo[1,2-a]quinoxaline derivatives are major microtubule-interfering agents with potent anticancer activity. In this study, the synthesis of several new derivatives of EAPB0503 is described, and the anticancer efficacy of 13 novel derivatives on A375 human melanoma cell line is reported. All new compounds show significant antiproliferative activity with IC50 in the range of 0.077-122μM against human melanoma cell line (A375). Direct inhibition of tubulin polymerization assay in vitro is also assessed. Results show that compounds 6b, 6e, 6g, and EAPB0503 highly inhibit tubulin polymerization with percentages of inhibition of 99%, 98%, 90%, and 84% respectively. Structure-activity relationship studies within the series are also discussed in line with molecular docking studies into the colchicine-binding site of tubulin.

Keywords: Antiproliferative activity; Human melanoma cancer cell line (A375); Imidazo[1,2-a]quinoxaline; Molecular docking; Structure–activity relationship; Tubulin depolymerization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Imidazoles / chemical synthesis
  • Imidazoles / chemistry
  • Imidazoles / pharmacology*
  • Melanoma / drug therapy*
  • Melanoma / pathology
  • Molecular Docking Simulation
  • Molecular Structure
  • Polymerization / drug effects
  • Quinoxalines / chemical synthesis
  • Quinoxalines / chemistry
  • Quinoxalines / pharmacology*
  • Structure-Activity Relationship
  • Tubulin / metabolism*
  • Tumor Cells, Cultured


  • Antineoplastic Agents
  • Imidazoles
  • Quinoxalines
  • Tubulin