title: Vanillin-derived antiproliferative compounds influence Plk1 activity.
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.
authors.affiliation: Institute of Pharmaceutical Chemistry, OSF/ZAFES/TMP, Johann-Wolfgang-Goethe University of Frankfurt, Max-von-Laue Str. 9, D-60438 Frankfurt, Germany.
authors.forename: Roberto
authors.initials: R
authors.lastname: Carrasco-Gomez
authors.affiliation: Eberhard-Karls-University Tübingen, Medical School, Department of Gynecology, Molecular Oncology and Gynecology, Calwer Str. 7, 72076 Tübingen, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Keppner-Witter
authors.affiliation: Institute of Pharmaceutical Chemistry, OSF/ZAFES/TMP, Johann-Wolfgang-Goethe University of Frankfurt, Max-von-Laue Str. 9, D-60438 Frankfurt, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Hieke
authors.affiliation: Friedrich-Schiller-University Jena, Institute for Biochemistry and Biophysics, Center for Molecular Biomedicine, Hans-Knöll-Straße 2, 07745 Jena, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Lange
authors.affiliation: Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Eidgenössische Technische Hochschule (ETH), Wolfgang-Pauli-Str. 10, 8093 Zürich, Switzerland.
authors.forename: Gisbert
authors.initials: G
authors.lastname: Schneider
authors.affiliation: Institute of Pharmaceutical Chemistry, OSF/ZAFES/TMP, Johann-Wolfgang-Goethe University of Frankfurt, Max-von-Laue Str. 9, D-60438 Frankfurt, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Schubert-Zsilavecz
authors.affiliation: 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.
authors.forename: Ewgenij
authors.initials: E
authors.lastname: Proschak
authors.affiliation: Friedrich-Schiller-University Jena, Institute for Biochemistry and Biophysics, Center for Molecular Biomedicine, Hans-Knöll-Straße 2, 07745 Jena, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Spänkuch
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001547:Benzaldehydes / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D011485:Protein Binding; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013329:Structure-Activity Relationship; D000097869:Polo-Like Kinase 1
chemical_list: D000970:Antineoplastic Agents; D001547:Benzaldehydes; D018797:Cell Cycle Proteins; D020033:Protein Isoforms; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C100058:vanillin
keywords: Antiproliferative compounds; Cell cycle; Polo-like kinase 1