Evaluation of 4-phenylamino-substituted naphthalene-1,2-diones as tubulin polymerization inhibitors

Bioorg Med Chem Lett. 2018 Oct 1;28(18):3057-3063. doi: 10.1016/j.bmcl.2018.07.047. Epub 2018 Aug 1.

Abstract

A series of 4-phenylamino-substituted naphthalene-1,2-dione derivatives were prepared and evaluated as effective antiproliferative agents. MTT assays showed that the compounds with a methyl group on the nitrogen linker exhibited potent antiproliferative activities against human cancer cells. The mechanistic study revealed that these compounds could induce mitochondrial depolarization, which resulted in intracellular ROS production, and they also acted as tubulin polymerization inhibitors. Moreover, the typical compound could arrest A549 cells in the G2/M phase, resulting in cellular apoptosis and induced mitotic arrest in A549 cells through disrupting microtubule dynamics.

Keywords: Antitumor agents; Mechanism; Reactive oxygen species; Tubulin polymerization inhibitors.

MeSH terms

  • A549 Cells
  • Aniline Compounds / chemistry
  • Aniline Compounds / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Naphthalenes / chemical synthesis
  • Naphthalenes / chemistry
  • Naphthalenes / pharmacology*
  • Polymerization / drug effects
  • Structure-Activity Relationship
  • Tubulin / metabolism*

Substances

  • Aniline Compounds
  • Antineoplastic Agents
  • Naphthalenes
  • Tubulin
  • naphthalene-1,2-dione