Synthesis, Antiproliferative and Cytotoxic Activities, DNA Binding Features and Molecular Docking Study of Novel Enamine Derivatives

Chem Biodivers. 2020 Jul;17(7):e2000139. doi: 10.1002/cbdv.202000139. Epub 2020 Jun 25.


Novel enamine derivatives were synthesized from the reaction of lactone and chalcones and their antiproliferative and cytotoxic activities against six cancer cell lines (e. g., HeLa, HT29, A549, MCF7, PC3 and Hep3B) and one normal cell lines (e. g., FL) were investigated along with their mode of interactions with CT-DNA. Most of the enamine derivatives with IC50 values of 86-168 μM demonstrated much stronger antiproliferative activity than the starting molecules against the cancer cells. While, among the enamine derivatives, four compounds displayed higher cytotoxic potency than the control drugs (5-fluorouracil and cisplatin) against the Hep3B cell lines, these compounds did not exhibit any significant toxicity against normal cells, FL. The UV/VIS spectral data suggest that eight compounds cause hypochromism with a slight bathochromic shift (∼6 nm), indicating that they bind to the DNA by way of an intercalative or minor groove binding mode. The binding constants of the compounds are in the range of 0.1×103 M-1 -2.3×104 M-1 . The antiproliferative activity of studied enamine derivatives could possibly be due to their DNA binding as well as their cytotoxic properties. In addition to these assays, the chalcones and enamine derivatives were investigated by molecular docking to calculate the synergistic effect of antiproliferative activities against six human cancer cell lines.

Keywords: antiproliferative activity; chalcone; cytotoxicity, molecular docking; enamine; lactone.

MeSH terms

  • Amines / chemical synthesis
  • Amines / chemistry
  • Amines / pharmacology*
  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Binding Sites / drug effects
  • Cattle
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • DNA / chemistry*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Docking Simulation*
  • Molecular Structure
  • Structure-Activity Relationship


  • Amines
  • Antineoplastic Agents
  • DNA
  • calf thymus DNA