Format

Send to

Choose Destination
Bioorg Med Chem Lett. 2014 Nov 1;24(21):5063-9. doi: 10.1016/j.bmcl.2014.09.015. Epub 2014 Sep 16.

Vanillin-derived antiproliferative compounds influence Plk1 activity.

Author information

1
Institute of Pharmaceutical Chemistry, OSF/ZAFES/TMP, Johann-Wolfgang-Goethe University of Frankfurt, Max-von-Laue Str. 9, D-60438 Frankfurt, Germany.
2
Eberhard-Karls-University Tübingen, Medical School, Department of Gynecology, Molecular Oncology and Gynecology, Calwer Str. 7, 72076 Tübingen, Germany.
3
Friedrich-Schiller-University Jena, Institute for Biochemistry and Biophysics, Center for Molecular Biomedicine, Hans-Knöll-Straße 2, 07745 Jena, Germany.
4
Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Eidgenössische Technische Hochschule (ETH), Wolfgang-Pauli-Str. 10, 8093 Zürich, Switzerland.
5
Institute of Pharmaceutical Chemistry, OSF/ZAFES/TMP, Johann-Wolfgang-Goethe University of Frankfurt, Max-von-Laue Str. 9, D-60438 Frankfurt, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Abstract

We synthesized a series of vanillin-derived compounds and analyzed them in HeLa cells for their effects on the proliferation of cancer cells. The molecules are derivatives of the lead compound SBE13, a potent inhibitor of the inactive conformation of human polo-like kinase 1 (Plk1). Some of the new designs were able to inhibit cancer cell proliferation to a similar extent as the lead structure. Two of the compounds ((({4-[(6-chloropyridin-3-yl)methoxy]-3-methoxyphenyl}methyl)(pyridin-4-ylmethyl)amine) and (({4-[(4-chlorophenyl)methoxy]-3-methoxyphenyl}methyl)(pyridin-4-ylmethyl)amine)) were much stronger in their capacity to reduce HeLa cell proliferation and turned out to potently induce apoptosis and reduce Plk1 kinase activity in vitro.

KEYWORDS:

Antiproliferative compounds; Cell cycle; Polo-like kinase 1

PMID:
25304894
DOI:
10.1016/j.bmcl.2014.09.015
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center