Anti-<i>Leishmania</i> and cytotoxic activities of perillaldehyde epoxide synthetic positional isomers

<p>Leishmaniasis belongs to a complex of zoonotic disease caused by protozoa of the genus <i>Leishmania</i> and is considered a major public health problem. Several essential oil chemical components have inhibitory effect against protozoa, including <i>Leishmania donovani</i>. Thus, the aim of this study was to evaluate for the first time the anti-<i>Leishmania</i> activity of two <i>p</i>-menthane monoterpene isomers (EPER-1: perillaldehyde 1,2-epoxide and EPER-2: perillaldehyde 8,9-epoxide) against <i>L. donovani</i> promastigotes as well as evaluating cytotoxic effect on mononuclear peripheral blood cells. Results of anti-<i>Leishmania</i> assay revealed that EPER-2 (IC<sub>50</sub> = 3.8 μg.mL<sup>−1</sup>) was 16-fold more potent than its isomer EPER-1 (IC<sub>50</sub> = 64.6 μg.mL<sup>−1</sup>). In contrast to PBMC cells, EPER-2 was not cytotoxic (IC<sub>50</sub> > 400 μg.mL<sup>−1</sup>) when compared to positive control. These data suggest that the disposition of epoxide group into the <i>p</i>-menthane skeleton affects the anti-<i>Leishmania</i> activity, being that the presence of the exocyclic epoxide group considerably increased potency. Thus, it was possible to observe that the location of the epoxide group into the <i>p</i>-menthane skeleton resulted in different potencies.</p>