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Antiplasmodial Activity of Alkaloids from Various Strychnos Species

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journal contribution
posted on 16.08.2002, 00:00 by Michel Frédérich, Marie-José Jacquier, Philippe Thépenier, Patrick De Mol, Monique Tits, Geneviève Philippe, Clément Delaude, Luc Angenot, Monique Zèches-Hanrot
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 (IC50 values ranging from 80 nM to 10 μM), longicaudatine-type (IC50 values ranging from 0.5 to 10 μM), matopensine-type (IC50 values ranging from 150 nM to 10 μM), 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 (IC50 values of 100−150 and 100−500 nM, respectively), and dihydrousambarensine (51) exhibited a 30-fold higher activity against the chloroquine-resistant strain (IC50 = 32 nM) than against the chloroquine-sensitive one.