Aspidosperma (Apocynaceae) plant cytotoxicity and activity towards malaria parasites. Part II: experimental studies with Aspidosperma ramiflorum in vivo and in vitro

Several species of Aspidosperma plants are used to treat diseases inthe tropics, including Aspidosperma ramiflorum, which acts againstleishmaniasis, an activity that is experimentally confirmed. The species, known asguatambu-yellow, yellow peroba,coffee-peroba andmatiambu, grows in the AtlanticForest of Brazil in the South to the Southeast regions. Through a guidedbiofractionation of A. ramiflorum extracts, the plant activityagainst Plasmodium falciparum was evaluated in vitro for toxicitytowards human hepatoma G2 cells, normal monkey kidney cells and nonimmortalised humanmonocytes isolated from peripheral blood. Six of the seven extracts tested wereactive at low doses (half-maximal drug inhibitory concentration < 3.8 µg/mL); theaqueous extract was inactive. Overall, the plant extracts and the purified compoundsdisplayed low toxicity in vitro. A nonsoluble extract fraction and one purifiedalkaloid isositsirikine (compound 5) displayed high selectivity indexes (SI) (= 56and 113, respectively), whereas compounds 2 and 3 were toxic (SI < 10). Thestructure, activity and low toxicity of isositsirikine in vitro are described herefor the first time in A. ramiflorum, but only the neutral andprecipitate plant fractions were tested for activity, which caused up to 53%parasitaemia inhibition of Plasmodium berghei in mice withblood-induced malaria. This plant species is likely to be useful in the furtherdevelopment of an antimalarial drug, but its pharmacological evaluation is stillrequired.