Killing resistant cancer cells with selective natural toxins

PhD defence, Friday 22 of September 2017. Nikolaj Lilholm Villadsen

2017.09.22 | Karen Konradi

Nikolaj Lilholm Villadsen

The natural products BE-43547A1 and rakicidin A have both been isolated from bacteria and synthesized via organics chemistry. Both natural products possess hypoxia-selective cytotoxicity a rare and interesting phenotype.

During his studies, Nikolaj – from Professor Thomas B. Poulen’s laboratory – has studied natural products from the APD-CLD family. These small molecules selectively kill cancer cells growing under low oxygen conditions – Hypoxic cancer cells. Tumour hypoxia is associated with resistance towards chemo- and radiotherapy and results in a poor patient prognosis. Nikolaj has (together with other members of the Poulsen lab) synthesized the natural products rakicidin A and BE-43547A1 along with analogues to study the underlying mechanism behind the hypoxia-selective cytotoxicity. The total synthesis efforts culminating in BE-43547A1 resulted in an incongruence between their data and the original Japanese patent. Isolation of the natural product from bacteria conclusively confirmed that the Poulsen labs data were correct, thus invalidating the patent data.

Currently, they are examining the biological mechanism of action of both natural products, while performing initial mouse studies, and aim to develop structurally simplified analogs with improved selectivity and shorter synthesis.

The PhD degree was completed at the Department of Chemistry, Science and Technology, Aarhus University.

This résumé was prepared by the PhD student.

Time: Friday 22 September 2017 at 14.15
Place: Building 1530, Auditorium F, Department of Mathematics, Aarhus University
Title of dissertation: Chemistry and Biology of the APD-CLD Natural Products
Contact information: Nikolaj L. Villadsen, e-mail: nlv@chem.au.dk, tel.: +45 60246173
Members of the assessment committee:
Professor David Spring, Department of Chemistry, University of Cambridge, United Kingdom
Professor Kristian Strømgaard, Center for Biopharmaceuticals, University of Copenhagen, Denmark
Professor Jacob Overgaard (chair), Department of Chemistry, Aarhus University
Main supervisor:
Professor Thomas B. Poulsen, Department of Chemistry, Aarhus University
Language: The PhD dissertation will be defended in English

The defence is public.
The dissertation is available for reading at the Graduate School of Science and Technology/GSST, Ny Munkegade 120, building 1520, rooms 128-134, 8000 Aarhus C.

PhD defence
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Revised 19.09.2017