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Bioorg Med Chem. 2017 Sep 1;25(17):4894-4903. doi: 10.1016/j.bmc.2017.07.039. Epub 2017 Jul 21.

Fluoro and pentafluorothio analogs of the antitumoral curcuminoid EF24 with superior antiangiogenic and vascular-disruptive effects.

Author information

1
Organic Chemistry Laboratory, University of Bayreuth, Universitaetsstrasse 30, 95447 Bayreuth, Germany.
2
Developmental Biology, University of Bayreuth, Universitaetsstrasse 30, 95447 Bayreuth, Germany.
3
University of Bucharest, Research Center for Integrated Analysis and Territorial Management, 4-12, Regina Elisabeta Avenue, Bucharest, 3rd district, 030018, Romania.
4
Organic Chemistry Laboratory, University of Bayreuth, Universitaetsstrasse 30, 95447 Bayreuth, Germany. Electronic address: Rainer.Schobert@uni-bayreuth.de.

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.

KEYWORDS:

Curcuminoids; NF-κB; Piperidone; Vascular disrupting agent (VDA); Zebrafish

PMID:
28774574
DOI:
10.1016/j.bmc.2017.07.039
[Indexed for MEDLINE]

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