Mendoza A., Perez-Silanes S., Quiliano M., Pabon A., Galiano S., Gonzalez G., Garavito G., Zimic M., Vaisberg A., Aldana I., Monge A., Deharo Eric. (2011). Aryl piperazine and pyrrolidine as antimalarial agents : synthesis and investigation of structure-activity relationships. Experimental Parasitology, 128 (2), p. 97-103. ISSN 0014-4894.
Titre du document
Aryl piperazine and pyrrolidine as antimalarial agents : synthesis and investigation of structure-activity relationships
Mendoza A., Perez-Silanes S., Quiliano M., Pabon A., Galiano S., Gonzalez G., Garavito G., Zimic M., Vaisberg A., Aldana I., Monge A., Deharo Eric
Source
Experimental Parasitology, 2011,
128 (2), p. 97-103 ISSN 0014-4894
Piperazine and pyrrolidine derivatives were synthesised and evaluated for their capacity to inhibit the growth of Plasmodium falciparum chloroquine-resistant (FCR-3) strain in culture. The combined presence of a hydroxyl group, a propane chain and a fluor were shown to be crucial for the antiplasmodial activity. Five compounds of the aryl-alcohol series inhibited 50% of parasite growth at doses <= 10 mu M. The most active compound 1-(4-fluoronaphthyl)-3-[4-(4-nitro-2-trifluoromethylphenyl)piperazin-1-y l] propan-1-ol was almost 20-40 times more active on P. falciparum (IC50: 0.5 mu M) than on tumorogenic and non-tumorogenic cells. In vivo it has a very weak effect; inhibiting 35% of parasite growth only, at 10 mg/kg/day against Plasmodium berghei infected mice without any impact on survival time. In silico molecular clocking study and molecular electrostatic potential calculation revealed that this compound bound to the active site of Plasmodium plasmepsin II enzyme.
