Antimalarial Potential of Neemlimonoids Against Plasmodiumfalciparum

Kadarkarai Murugan and Chellasamy Panneerselvam

Objective: The antiplasmodial activity of pure ne am l imono ids (azadirachtin, salannin, deacetylgedunin, gedunin, 17-hydroxyazadiradione 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, 17- hydroxyazadiradione 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 prepared by dilution with isopropanol tested against P. falciparum. Resul ts: 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 synchronization r ing 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 neems 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 antimalar ials with transmission-blocking potential, as well as permitting the further study of structure-activity relationships in these compounds.