Synthesis and Anticancer Properties of Oxazepines Related to Azaisoerianin and IsoCoQuines

ChemMedChem. 2020 Aug 19;15(16):1571-1578. doi: 10.1002/cmdc.202000197. Epub 2020 Jun 24.

Abstract

In this article, we report the synthesis and biological properties of a series of novel oxazepines related to isoCA-4 having significant antitumor properties. Among them, three oxazepin-9-ol derivatives display a nanomolar or a sub-nanomolar cytotoxicity level against five human cancer cell lines (HCT116, U87, A549, MCF7, and K562). It was demonstrated that the lead compound in this series inhibits tubulin assembly with an IC50 value of 1 μM and totally arrests the cellular cycle in the G2/M phase at the low concentration of 5 nM in HCT116 and K562 cells. Molecular modeling studies perfectly corroborates these promising results.

Keywords: cancer; cytotoxicity; isoCA-4; oxazepine; quinoline.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Aza Compounds / chemistry
  • Aza Compounds / pharmacology*
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Oxazepines / chemical synthesis
  • Oxazepines / chemistry
  • Oxazepines / pharmacology*
  • Structure-Activity Relationship
  • Tubulin / metabolism*
  • Tubulin Modulators / chemical synthesis
  • Tubulin Modulators / chemistry
  • Tubulin Modulators / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Aza Compounds
  • Oxazepines
  • Tubulin
  • Tubulin Modulators