Antimalarial Potential of Neem Limonoids against Plasmodium Falciparum

Received 10th December, 2012 Received in revised form 20th, December, 2012 Accepted 5th January, 2013 Published online 31 January, 2013 Objective: The antiplasmodial activity of pure n e e m l i m o n o i d s (azadirachtin, salannin, deacetylgedunin, gedunin, 17-h ydroxyazadiradione and deacetylnimbin) was evaluated in vitro against the chloroquine resistant and-sensitive strains of P. falciparum Methods: Six neem limonoids (purity > 99%) namely azadirachtin, salannin,deacetylgedunin, gedunin, 17hydroxyazadiradione and deacetylnimbin were sent from M. Ishida, Central Research Laboratories, Taiyo Kagaku Co. Ltd., Japan. They were dissolved in isopropanol and different concentrations such as 25, 50 and 75 μg/ml were p repared by dilution with isopropanol tested against P. falciparum . R esults: The Inhibitory Concentration (50) obtained in vitro on human malaria strain ranged from sensitive 1.37%; resistance 3.13% at 75 μg /ml with Azadirachtin. From the six limonoids Azadirachtin, salannin and deacetylgedunin showed high inhibitory activity at all doses, while the rest of the neem limonoids were less active, and were only biologically active at high doses. By s ynchronization ri n g stage of parasites suggested as the susceptible target stages to various neem compounds. In addition, all the maturation stages of gametocytes were also killed by various neem fractions tested. The anti-plasmodial effect of neem components was also observed on parasites previously shown to be resistant to other antimalarial drugs, i.e. chloroquine and pyrimethamine suggesting a different mode of action. Conclusion: These findings raise the possibility of developing azadirachtinbased compounds as antimalarials with transmission-blocking potential, as well as p ermitting the further study of structure-activity relationships in these compounds.