1. Fluoro and pentafluorothio analogs of the antitumoral curcuminoid EF24 with superior antiangiogenic and vascular-disruptive effects.
- Author
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Schmitt F, Gold M, Begemann G, Andronache I, Biersack B, and Schobert R
- Subjects
- Angiogenesis Inhibitors chemical synthesis, Angiogenesis Inhibitors chemistry, Angiogenesis Inhibitors pharmacology, Antineoplastic Agents chemical synthesis, Cell Line, Tumor, Cell Movement drug effects, Cell Proliferation drug effects, Cell Survival drug effects, Curcumin chemical synthesis, 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, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Curcumin analogs & derivatives, Curcumin pharmacology
- 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 IC
50 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., (Copyright © 2017 Elsevier Ltd. All rights reserved.)- Published
- 2017
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