title: Antiplasmodial activity of alkaloids from various strychnos species.
abstract: The in vitro antiplasmodial activities of 69 alkaloids from various Strychnos species were evaluated against chloroquine-resistant and chloroquine-sensitive lines of Plasmodium falciparum. The compounds, comprising mainly indolomonoterpenoid alkaloids, exhibited a wide range of biological potencies in the antiplasmodial assays. The most active alkaloids were also tested for cytotoxicity against HCT-116 colon cancer cells to determine their antiplasmodial selectivity. As a result of these studies, structure-activity relationships for these alkaloids have begun to emerge. Alkaloids presenting four types of bisindole skeleton exhibited potent and selective activities against Plasmodium. They were sungucine-type (IC(50) values ranging from 80 nM to 10 microM), longicaudatine-type (IC(50) values ranging from 0.5 to 10 microM), matopensine-type (IC(50) values ranging from 150 nM to 10 microM), and usambarine-type alkaloids. Within the last structural type, isostrychnopentamine (49) and ochrolifuanine A (46) were found to be active against chloroquine-sensitive and -resistant strains (IC(50) values of 100-150 and 100-500 nM, respectively), and dihydrousambarensine (51) exhibited a 30-fold higher activity against the chloroquine-resistant strain (IC(50) = 32 nM) than against the chloroquine-sensitive one.
authors.affiliation: University of Liège, Natural and Synthetic Drugs Research Center, Laboratory of Pharmacognosy, Avenue de l'Hôpital 1, B36, B-4000 Liège, Belgium. M.Frederich@ulg.ac.be
authors.forename: Michel
authors.initials: M
authors.lastname: Frédérich
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Jacquier
authors.forename: Philippe
authors.initials: P
authors.lastname: Thépenier
authors.forename: Patrick
authors.initials: P
authors.lastname: De Mol
authors.forename: Monique
authors.initials: M
authors.lastname: Tits
authors.forename: Geneviève
authors.initials: G
authors.lastname: Philippe
authors.forename: Clément
authors.initials: C
authors.lastname: Delaude
authors.forename: Luc
authors.initials: L
authors.lastname: Angenot
authors.forename: Monique
authors.initials: M
authors.lastname: Zèches-Hanrot
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship; D031451:Strychnos / Q000737:chemistry*
chemical_list: D000470:Alkaloids; D000962:Antimalarials