Design of novel artemisinin‐like derivatives with cytotoxic and anti‐angiogenic properties |
| |
Authors: | Shahid Soomro Tobias Langenberg Anne Mahringer V Badireenath Konkimalla Cindy Horwedel Pavlo Holenya Almut Brand Canan Cetin Gert Fricker Mieke Dewerchin Peter Carmeliet Edward M Conway Herwig Jansen Thomas Efferth |
| |
Institution: | 1. Dafra Pharma Research & Development, Slachthuisstraat, Turnhout, Belgium;2. KU Leuven, VIB Vesalius Research Center, Herestraat, Leuven, Belgium;3. Institute for Pharmacy and Molecular Biotechnology, University of Heidelberg, Im Neuenheimer Feld, Heidelberg, Germany;4. German Cancer Research Center, Pharmaceutical Biology, Im Neuenheimer Feld, Heidelberg, Germany;5. Centre for Blood Research, Department of Medicine, University of British Columbia, Vancouver, BC, Canada;6. Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Mainz, Germany |
| |
Abstract: | Artemisinins are plant products with a wide range of medicinal applications. Most prominently, artesunate is a well tolerated and effective drug for treating malaria, but is also active against several protozoal and schistosomal infections, and additionally exhibits anti‐angiogenic, anti‐tumorigenic and anti‐viral properties. The array of activities of the artemisinins, and the recent emergence of malaria resistance to artesunate, prompted us to synthesize and evaluate several novel artemisinin‐like derivatives. Sixteen distinct derivatives were therefore synthesized and the in vitro cytotoxic effects of each were tested with different cell lines. The in vivo anti‐angiogenic properties were evaluated using a zebrafish embryo model. We herein report the identification of several novel artemisinin‐like compounds that are easily synthesized, stable at room temperature, may overcome drug‐resistance pathways and are more active in vitro and in vivo than the commonly used artesunate. These promising findings raise the hopes of identifying safer and more effective strategies to treat a range of infections and cancer. |
| |
Keywords: | malaria cancer drug resistance P‐glycoprotein chemotherapy |
|
|