Aplysinopsin analogs: Synthesis and anti-proliferative activity of substituted (Z)-5-(N-benzylindol-3-ylmethylene)imidazolidine-2,4-diones

Bioorg Med Chem. 2010 May 15;18(10):3570-4. doi: 10.1016/j.bmc.2010.03.054. Epub 2010 Mar 27.

Abstract

A series of substituted (Z)-5-(N-benzylindol-3-ylmethylene)imidazolidine-2,4-dione (3) analogs structurally related to aplysinopsin, and that incorporate a variety of substituents in both the indole and N-benzyl moieties have been synthesized under microwave irradiation and conventional heating methods These analogs were evaluated for their anti-proliferative activity against MCF-7 and MDA-231 breast cancer cell lines, and A549 and H460 lung cancer cell lines. Two analogs, 3f and 3j had IC(50) values of 4.4 and 5.2microM, respectively, compared to 5-fluorouracil (IC(50)=15.2microM) against MCF-7 cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects*
  • Drug Design
  • Drug Screening Assays, Antitumor / methods*
  • Humans
  • Imidazolidines / chemical synthesis
  • Imidazolidines / pharmacology*
  • Indoles / chemistry
  • Inhibitory Concentration 50
  • Structure-Activity Relationship
  • Tryptophan / analogs & derivatives*
  • Tryptophan / chemical synthesis
  • Tryptophan / chemistry
  • Tryptophan / pharmacology

Substances

  • Antineoplastic Agents
  • Imidazolidines
  • Indoles
  • imidazolidine-2,4-dione
  • aplysinopsin
  • Tryptophan