Design of novel artemisinin-like derivatives with cytotoxic and anti-angiogenic properties.
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.
Soomro
Shahid
S
Dafra Pharma Research & Development, Slachthuisstraat, Turnhout, Belgium.
Langenberg
Tobias
T
Mahringer
Anne
A
Konkimalla
V Badireenath
VB
Horwedel
Cindy
C
Holenya
Pavlo
P
Brand
Almut
A
Cetin
Canan
C
Fricker
Gert
G
Dewerchin
Mieke
M
Carmeliet
Peter
P
Conway
Edward M
EM
Jansen
Herwig
H
Efferth
Thomas
T
D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D031172:Artemisia annua / Q000737:chemistry; D037621:Artemisinins / Q000737:chemistry* / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004351:Drug Resistance; D005434:Flow Cytometry; D010936:Plant Extracts / Q000737:chemistry; D013329:Structure-Activity Relationship; D013552:Swine; D015027:Zebrafish / Q000196:embryology
D020533:Angiogenesis Inhibitors; D037621:Artemisinins; D010936:Plant Extracts; C031327:artemisinin