title: Design of novel artemisinin-like derivatives with cytotoxic and anti-angiogenic properties.
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.
authors.affiliation: Dafra Pharma Research & Development, Slachthuisstraat, Turnhout, Belgium.
authors.forename: Shahid
authors.initials: S
authors.lastname: Soomro
authors.forename: Tobias
authors.initials: T
authors.lastname: Langenberg
authors.forename: Anne
authors.initials: A
authors.lastname: Mahringer
authors.forename: V Badireenath
authors.initials: VB
authors.lastname: Konkimalla
authors.forename: Cindy
authors.initials: C
authors.lastname: Horwedel
authors.forename: Pavlo
authors.initials: P
authors.lastname: Holenya
authors.forename: Almut
authors.initials: A
authors.lastname: Brand
authors.forename: Canan
authors.initials: C
authors.lastname: Cetin
authors.forename: Gert
authors.initials: G
authors.lastname: Fricker
authors.forename: Mieke
authors.initials: M
authors.lastname: Dewerchin
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
authors.forename: Edward M
authors.initials: EM
authors.lastname: Conway
authors.forename: Herwig
authors.initials: H
authors.lastname: Jansen
authors.forename: Thomas
authors.initials: T
authors.lastname: Efferth
mesh_terms: 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
chemical_list: D020533:Angiogenesis Inhibitors; D037621:Artemisinins; D010936:Plant Extracts; C031327:artemisinin