The project is concerned with the two structurally similar natural products scytonemin and nostodione A, which are found in cyanobacteria. Scytonemin has been established to act as a sunscreen, protecting the proteins and DNA in bacteria from the harmful solar UV radiation. Scytonemin has also been characterized as an inhibitor of the polo-like kinase 1 (plk1). Other substances with this inhibitory property are currently in clinical trials for treatment of different cancers.
Increased awareness of the escalating rate of skin cancers has caused increased use of sunscreen products among the general public. This in turn has led to more cases of allergies to the UV-filters found in such products, one of several problems with existing UV-filters. The primary aim of the project is to explore scytonemin as a blueprint for new, safer and more effective UV-filters. The secondary aim is to investigate the biological activity of scytonemin, which in the future could provide potent kinase inhibitors. The project also serves as a platform for improvement and development of new tools (chemical reactions) by which elaborate organic molecules, like scytonemin, can be assembled.
The project involves total syntheses of the natural products together with analogues of them. These compounds are then explored with respect to their photophysical properties as well as their plk1 inhibitory effects. The synthetic framework relies heavily on metal catalysis, where palladium, ruthenium and gold are utilized as catalysts. The photophysical properties are studied using different spectroscopic methods.
Anna Börje, Dermatochemistry, University of Gothenburg
The project is performed within the Centre for Skin Research (SkinResQU) at Chalmers and University of Gothenburg.
The Swedish Research Council