Multicomponent Domino Synthesis, Anticancer Activity and Molecular Modeling Simulation of Complex Dispirooxindolopyrrolidines

Molecules. 2018 May 5;23(5):1094. doi: 10.3390/molecules23051094.

Abstract

A series of spirooxindolopyrrolidine fused N-styrylpiperidone heterocyclic hybrids has been synthesized in excellent yield via a domino multicomponent protocol that involves one-pot three component 1,3-dipolar cycloaddition and concomitant enamine reactions performed in an inexpensive ionic liquid, namely 1-butyl-3-methylimidazolium bromide ([bmim]Br). Compounds thus synthesized were evaluated for their cytotoxicity against U-937 tumor cells. Interestingly; compounds 5i and 5m exhibited a better cytotoxicity than the anticancer drug bleomycin. In addition; the effect of the synthesized compounds on the nuclear morphology of U937 FaDu cells revealed that treatment with compounds 5am led to their apoptotic cell death.

Keywords: 1,3-dipolar cycloaddition; cytotoxicity assays; domino reaction; ionic liquids; molecular docking.

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Binding Sites
  • Bleomycin / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cycloaddition Reaction
  • Drug Design
  • Humans
  • Imidazoles / chemistry
  • Indoles / chemical synthesis*
  • Indoles / pharmacology
  • Inhibitory Concentration 50
  • Lymphocytes / drug effects
  • Lymphocytes / pathology
  • Molecular Docking Simulation
  • Piperidones / chemical synthesis*
  • Piperidones / pharmacology
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Structure, Secondary
  • Proto-Oncogene Proteins c-met / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-met / chemistry
  • Proto-Oncogene Proteins c-met / metabolism
  • Pyrrolidines / chemical synthesis*
  • Pyrrolidines / pharmacology
  • Spiro Compounds / chemical synthesis*
  • Spiro Compounds / pharmacology
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Imidazoles
  • Indoles
  • Piperidones
  • Pyrrolidines
  • Spiro Compounds
  • Bleomycin
  • 1-butyl-3-methylimidazolium chloride
  • MET protein, human
  • Proto-Oncogene Proteins c-met