Open AccessDesign of novel artemisinin‐like derivatives with cytotoxic and anti‐angiogenic properties
Author(s) -
Soomro Shahid,
Langenberg Tobias,
Mahringer Anne,
Konkimalla V. Badireenath,
Horwedel Cindy,
Holenya Pavlo,
Brand Almut,
Cetin Canan,
Fricker Gert,
Dewerchin Mieke,
Carmeliet Peter,
Conway Edward M.,
Jansen Herwig,
Efferth Thomas
Publication year - 2011
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2010.01120.x
Subject(s) - artesunate , artemisinin , in vivo , malaria , dihydroartemisinin , pharmacology , biopharmaceutical , plasmodium falciparum , drug , drug resistance , biology , immunology , microbiology and biotechnology
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.