title: In vitro antiplasmodial activity of abietane and totarane diterpenes isolated from Harpagophytum procumbens (devil's claw).
abstract: The development of drug resistance and resurgence of malaria has highlighted the need for new chemically diverse antimalarial drugs. This study investigates Harpagophytum procumbens DC. as a source of antiplasmodial hit compounds. The roots of wild harvested plants as well as the aerial sections, seeds and roots of cultivated H. procumbens were evaluated for in vitro antiplasmodial activity. Bioassay-guided fractionation of the petroleum ether root extract yielded two diterpenes, (+)-8,11,13-totaratriene-12,13-diol (1) and (+)-8,11,13-abietatrien-12-ol (2). Compounds 1 and 2 displayed significant (IC50 < 1 microg/mL) in vitro antiplasmodial activity against a chloroquine-resistant (K1) and -sensitive (D10) strain of Plasmodium falciparum, and low cytotoxicity (SI > 65) against two mammalian cell lines (CHO and HepG2). It was found that 1 and 2 did not modify the erythrocyte shape, which in conjunction with the cytotoxicity results, indicates selective antiplasmodial activity.
authors.affiliation: Pharmacology Division, Department of Medicine, University of Cape Town, Groote Schuur Hospital, Cape Town, South Africa.
authors.forename: Cailean
authors.initials: C
authors.lastname: Clarkson
authors.forename: William E
authors.initials: WE
authors.lastname: Campbell
authors.forename: Peter
authors.initials: P
authors.lastname: Smith
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line / Q000187:drug effects; D004224:Diterpenes / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004351:Drug Resistance; D004912:Erythrocytes / Q000187:drug effects; D031684:Harpagophytum; D006801:Humans; D020128:Inhibitory Concentration 50; D016778:Malaria, Falciparum / Q000188:drug therapy; D008517:Phytotherapy; D035261:Plant Components, Aerial; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018517:Plant Roots; D010963:Plasmodium falciparum / Q000187:drug effects*; D012639:Seeds
chemical_list: D000962:Antimalarials; D004224:Diterpenes; D010936:Plant Extracts