Antiplasmodial activity of iron(II) and ruthenium(II) organometallic complexes against Plasmodium falciparum blood parasites

This work reports the in vitro activity against Plasmodiumfalciparumblood forms (W2 clone, chloroquine-resistant) oftamoxifen-based compounds and their ferrocenyl (ferrocifens) and ruthenocenyl(ruthenocifens) derivatives, as well as their cytotoxicity against HepG2 humanhepatoma cells. Surprisingly with these series, results indicate that the biologicalactivity of ruthenocifens is better than that of ferrocifens and other tamoxifen-likecompounds. The synthesis of a new metal-based compound is also described. It wasshown, for the first time, that ruthenocifens are good antiplasmodial prototypes.Further studies will be conducted aiming at a better understanding of their mechanismof action and at obtaining new compounds with better therapeutic profile.     

Aspidosperma (Apocynaceae) plant cytotoxicity and activity towards malaria parasites. Part I: Aspidosperma nitidum (Benth) used as a remedy to treat fever and malaria in the Amazon

Infusions of Aspidosperma nitidum (Apocynaceae) wood bark are used to treat fever and malaria in the Amazon Region. Several species of this family are known to possess indole alkaloids and other classes of secondary metabolites, whereas terpenoids, an inositol and the indole alkaloids harmane-3 acid and braznitidumine have been described in A. nitidum . In the present study, extracts from the wood bark, leaves and branches of this species were prepared for assays against malaria parasites and cytotoxicity testing using human hepatoma and normal monkey kidney cells. The wood bark extracts were active against Plasmodium falciparum and showed a low cytotoxicity in vitro, whereas the leaf and branch extracts and the pure alkaloid braznitidumine were inactive. A crude methanol extract was subjected to acid-base fractionation aimed at obtaining alkaloid-rich fractions, which were active at low concentrations against P. falciparum and in mice infected with and sensitive Plasmodium berghei parasites. Our data validate the antimalarial usefulness of A. nitidum wood bark, a remedy that can most likely help to control malaria. However, the molecules responsible for this antimalarial activity have not yet been identified. Considering their high selectivity index, the alkaloid-rich fractions from the plant bark might be useful in the development of new antimalarials.