Effect of 3‐Alkylpyridine Marine Alkaloid Analogues in Leishmania Species Related to American Cutaneous Leishmaniasis

A series of oxygenated analogues of marine 3‐alkylpyridine alkaloids were synthesized, and their leishmanicidal activity was assayed. All compounds were prepared from 3‐pyridinepropanol in few steps and in good yields. The key step for the synthesis of these compounds was a classic Williamson etherification under phase‐transfer conditions. Besides toxicity in peritoneal macrophages, the compounds exhibited a significant leishmanicidal activity. Of twelve compounds tested, five showed a strong leishmanicidal activity against promastigote forms of Leishmania amazonensis and L. braziliensis with IC₅₀ below 10 μm . Compounds 11 , 14 , 15, and 16 showed a strong leishmanicidal activity on intracellular amastigotes (IC₅₀ values of 2.78; 0.27; 1.03, and 1.33 μm , respectively), which is unlikely to be owing to the activation of nitric oxide production by macrophages.