ZFIN ID: ZDB-PUB-170805-8
Fluoro and pentafluorothio analogs of the antitumoral curcuminoid EF24 with superior antiangiogenic and vascular-disruptive effects
Schmitt, F., Gold, M., Begemann, G., Andronache, I., Biersack, B., Schobert, R.
Date: 2017
Source: Bioorganic & Medicinal Chemistry   25(17): 4894-4903 (Journal)
Registered Authors: Begemann, Gerrit
Keywords: Curcuminoids, NF-κB, Piperidone, Vascular disrupting agent (VDA), Zebrafish
MeSH Terms:
  • Angiogenesis Inhibitors/chemical synthesis
  • Angiogenesis Inhibitors/chemistry
  • Angiogenesis Inhibitors/pharmacology
  • Antineoplastic Agents/chemical synthesis
  • Antineoplastic Agents/chemistry*
  • Antineoplastic Agents/pharmacology*
  • Cell Line, Tumor
  • Cell Movement/drug effects
  • Cell Proliferation/drug effects
  • Cell Survival/drug effects
  • Curcumin/analogs & derivatives*
  • Curcumin/chemical synthesis
  • Curcumin/pharmacology*
  • Drug Screening Assays, Antitumor
  • Fluorine/chemistry
  • G2 Phase Cell Cycle Checkpoints/drug effects
  • HT29 Cells
  • Humans
  • M Phase Cell Cycle Checkpoints/drug effects
  • NF-kappa B/metabolism
  • Neovascularization, Physiologic/drug effects
  • Stereoisomerism
PubMed: 28774574 Full text @ Bioorg. Med. Chem.
ABSTRACT
A series of 14 analogs of the curcuminoid EF24, (3E,5E)-3,5-bis[(2-fluorophenyl)methylene]-4-piperidinone, bearing fluorine or pentafluorothio substituents, were prepared and tested for antiproliferative, vascular-disruptive, and antiangiogenic activity, as well as for their influence on other cancer-relevant targets. They proved antiproliferative against eight cancer cell lines with IC50 values in the low single-digit micromolar to triple-digit nanomolar range. Like EF24, the hexafluoro 3c and 3d and bis(pentafluorothio) 4f derivatives arrested HT-29 colon carcinoma cells in G2/M phase of the cell cycle, yet inhibited angiogenesis, e.g. in zebrafish larvae, to a much greater extent. The antimigratory effects in 518A2 melanoma cells of 3c, its regioisomer 3d, and of 4f, originate from an inhibition of NF-κB translocation. Moreover, 3c and 3d showed potential as vascular-disruptive agents in chorioallantoic/vitelline membrane (CA/VM) assays.
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