Curcumin inspired 2-chloro/phenoxy quinoline analogues: Synthesis and biological evaluation as potential anticancer agents

Bioorg Med Chem Lett. 2018 Mar 1;28(5):892-898. doi: 10.1016/j.bmcl.2018.01.070. Epub 2018 Feb 2.

Abstract

Synthesis of twenty new curcumin inspired 2-chloro/phenoxy quinoline derivatives is outlined in this study. The obtained new chemical entities were screened in vitro for their cytotoxic activity towards various tumor cell lines. Of the compounds screened, 6c and 9d exhibited significant activity and the most active analogue 6c displayed promising cytotoxicity against PC-3 (IC50 of 3.12 ± 0.11 μM), DU-145, NCI-H460 and 4 T1 cell lines. Further, 6c and 9d have 2.1 and 1.4 times more aqueous solubility, respectively, than curcumin. Additionally, the promising candidate 6c could induce G2/M cell cycle arrest and apoptosis in PC-3 cells, as determined by AO-EB staining, DAPI staining, analysis of ROS levels as well as annexin binding assay.

Keywords: 2-Substituted quinolines; Anticancer; Apoptosis; Claisen-Schmidt condensation; Curcumin mimics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Curcumin / chemistry
  • Curcumin / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Quinolines / chemistry
  • Quinolines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Quinolines
  • quinoline
  • Curcumin