title: Antiplasmodial and antitumor activity of dihydroartemisinin analogs derived via the aza-Michael addition reaction.
abstract: A series of dihydroartemisinin derivatives were synthesized via an aza-Michael addition reaction to a dihydroartemisinin-based acrylate and were evaluated for antiplasmodial and antitumor activity. The target compounds showed excellent antiplasmodial activity, with dihydroartemisinin derivatives 5, 7, 9 and 13 exhibiting IC(50) values of ≤10 nM against both D10 and Dd2 strains of Plasmodium falciparum. Derivative 4d was the most active against the HeLa cancer cell line, with an IC(50) of 0.37 μM and the highest tumor specificity.
authors.affiliation: Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa.
authors.forename: Tzu-Shean
authors.initials: TS
authors.lastname: Feng
authors.forename: Eric M
authors.initials: EM
authors.lastname: Guantai
authors.forename: Margo J
authors.initials: MJ
authors.lastname: Nell
authors.forename: Constance E J
authors.initials: CE
authors.lastname: van Rensburg
authors.forename: Heinrich C
authors.initials: HC
authors.lastname: Hoppe
authors.forename: Kelly
authors.initials: K
authors.lastname: Chibale
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D037621:Artemisinins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001372:Aza Compounds / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects*
chemical_list: D000962:Antimalarials; D000970:Antineoplastic Agents; D037621:Artemisinins; D001372:Aza Compounds; C039060:artenimol