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.
- 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.
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.