|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.
|Source:||Bioorganic & Medicinal Chemistry 25(17): 4894-4903 (Journal)|
|Registered Authors:||Begemann, Gerrit|
|Keywords:||Curcuminoids, NF-κB, Piperidone, Vascular disrupting agent (VDA), Zebrafish|
|PubMed:||28774574 Full text @ Bioorg. Med. Chem.|
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.
ABSTRACTA 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.