PUBLICATION
Fluoro and pentafluorothio analogs of the antitumoral curcuminoid EF24 with superior antiangiogenic and vascular-disruptive effects
- Authors
- Schmitt, F., Gold, M., Begemann, G., Andronache, I., Biersack, B., Schobert, R.
- ID
- ZDB-PUB-170805-8
- 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.
Citation
Schmitt, F., Gold, M., Begemann, G., Andronache, I., Biersack, B., Schobert, R. (2017) Fluoro and pentafluorothio analogs of the antitumoral curcuminoid EF24 with superior antiangiogenic and vascular-disruptive effects. Bioorganic & Medicinal Chemistry. 25(17):4894-4903.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping