2. Academic Validation
  3. Vanillin-derived antiproliferative compounds influence Plk1 activity

Vanillin-derived antiproliferative compounds influence Plk1 activity

  • Bioorg Med Chem Lett. 2014 Nov 1;24(21):5063-9. doi: 10.1016/j.bmcl.2014.09.015.
Roberto Carrasco-Gomez 1,  Sarah Keppner-Witter 2,  Martina Hieke 1,  Lisa Lange 3,  Gisbert Schneider 4,  Manfred Schubert-Zsilavecz 1,  Ewgenij Proschak 5,  Birgit Spänkuch 3
Affiliations

Affiliations

  • 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.
PMID: 25304894 DOI: 10.1016/j.bmcl.2014.09.015
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.

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