title: Indole and aminoimidazole moieties appear as key structural units in antiplasmodial molecules.
abstract: From a library of compounds of natural sources, a big series of molecules was chosen by random sampling to evaluate their in vitro antimalarial activity against Plasmodium falciparum and their antifungal activity against Candida sp. From 184 molecules tested, no molecules were active against Candida sp. (MIC>10μg/ml) whereas 13 clearly showed high antiplasmodial activity in vitro, with an IC(50) less than 1μg/ml against the chloroquine-resistant strain of P. falciparum FcM29-Cameroon. The molecules with the best antiplasmodial efficacy were 10-hydroxy-ellipticin (IC(50): 0.08μg/ml), tchibangensin (IC(50): 0.13μg/ml), ellipticin hydrochloride (IC(50): 0.17μg/ml), usambarensin (IC(50): 0.23μg/ml), 7S,3S-ochropposinine oxindole (IC(50): 0.25μg/ml), 3,14-dihydro-ellipticin (IC(50): 0.25μg/ml), tetrahydro-4',5',6'17-usambarensin 17S (IC(50): 0.26μg/ml), ellipticine (IC(50): 0.28μg/ml), aricin (IC(50): 0.3μg/ml), 10-methoxy-ellipticin (IC(50): 0.32μg/ml), aplysinopsin (IC(50): 0.43μg/ml), descarbomethoxydihydrogambirtannin (IC(50): 0.46μg/ml) and ochrolifuanin A (IC(50): 0.47μg/ml). Among these 13 promising molecules, all except descarbomethoxydihydrogambirtannin, ochrolifuanine A and usambarensine presented here novel biological activities since they had never been described in the literature for their antiplasmodial activity. In spite of the large diversity of the molecules which have been tested, it is interesting to note that the ones active against Plasmodium are all indole derivatives (and one is both indolic and aminoimidazolic). To find new antiplasmodial compounds, ethnopharmacological approaches studying traditional medicine treatments for malaria is largely used but random research produced here an interesting yield (7%) of new antiplasmodial hits and appears therefore complementary to the traditional medicine way.
authors: CNRS, LCC (Laboratoire de Chimie de Coordination) UPR8241, 205, route de Narbonne, F-31077 Toulouse, France.
authors: Charlotte
authors: C
authors: Passemar
authors: Mariette
authors: M
authors: Saléry
authors: Patrice Njomnang
authors: PN
authors: Soh
authors: Marie-Denise
authors: MD
authors: Linas
authors: Alain
authors: A
authors: Ahond
authors: Christiane
authors: C
authors: Poupat
authors: Françoise
authors: F
authors: Benoit-Vical