Six limonoids [kotschyienone A and B (1, 2), 7-deacetylgedunin (3), 7-deacetyl-7-oxogedunin (4), andirobin (5) and methyl angolensate (6)] were investigated for their trypanocidal and leishmanicidal activities using bloodstream forms of Trypanosoma brucei and promastigotes of Leishmania major. Whereas all compounds showed anti-trypanosomal activity, only compounds 1-4 displayed anti-leishmanial activity. The 50% growth inhibition (GI50) values for the trypanocidal and leishmanicidal activity of the compounds ranged between 2.5 and 14.9 μM. Kotschyienone A (1) was found to be the most active compound with a minimal inhibition concentration (MIC) value of 10 μM and GI50 values between 2.5 and 2.9 μM. Only compounds 1 and 3 showed moderate cytotoxicity against HL-60 cells with MIC and GI50 values of 100 μM and 31.5-46.2 μM, respectively. Compound 1 was also found to show activity against intracellular amastigotes of L. major with a GI50 value of 1.5 μM. The results suggest that limonoids have potential as drug candidates for the development of new treatments against trypanosomiasis and leishmaniasis.
Keywords: African trypanosomiasis; Leishmania major; Leishmaniasis; Limonoids; Trypanosoma brucei.