Immunomodulatory and Antileishmanial Activity of Phenylpropanoid Dimers Isolated from <i>Nectandra leucantha</i>

Three phenylpropanoid dimers (<b>1</b>–<b>3</b>) including two new metabolites were isolated from the extract of the twigs of <i>Nectandra leucantha</i> using antileishmanial bioassay-guided fractionation. The in vitro antiparasitic activity of the isolated compounds against <i>Leishmania</i> <i>donovani</i> parasites and mammalian cytotoxicity and immunomodulatory effects were evaluated. Compounds <b>1</b>–<b>3</b> were effective against the intracellular amastigotes within macrophages, with IC₅₀ values of 26.7, 17.8, and 101.9 μM, respectively. The mammalian cytotoxicity, given by the 50% cytotoxic concentration (CC₅₀), was evaluated against peritoneal macrophages. Compounds <b>1</b> and <b>3</b> were not toxic up to 290 μM, whereas compound <b>2</b> demonstrated a CC₅₀ value of 111.2 μM. Compounds <b>1</b>–<b>3</b> also suppressed production of disease exacerbatory cytokines IL-6 and IL-10 but had minimal effect on nitric oxide production in <i>L.</i> <i>donovani-</i>infected macrophages, indicating that antileishmanial activity of these compounds is mediated via an NO-independent mechanism. Therefore, these new natural products could represent promising scaffolds for drug design studies for leishmaniasis