Antileishmanial activity of amides from Piper amalago L. derivative, and synthetic analogs

Amides (1–2) were isolated from the chloroform extract of Piper amalago L. leaves. A derivative (3) and synthetic analogs (4–6) were prepared and all the compounds were tested against the promastigote and intracellular amastigote forms of Leishmania amazonensis. The cytotoxicity toward the J774A1 macrophages and the ability to induce nitric oxide production were also investigated. Compound 2 was the most active of all the compounds against the promastigote and intracellular amastigote forms with IC₅₀ values of 15µM and 14.5µM, respectively. None of the compounds modulated the production of nitric oxide, suggesting a direct mechanism of action on Leishmania.