Antileishmanial activity and immunomodulatory effect of secosubamolide, a butanolide isolated from Nectandra oppositifolia (Lauraceae)

Background: Visceral leishmaniasis is a complex neglected tropical disease caused by Leishmania donovani complex. Its current treatment reveals strong limitations, especially high toxicity. In this context, natural products are important sources of new drug alternatives for VL therapy. Therefore, the antileishmanial and immunomodulatory activity of compounds isolated from Nectandra oppositifolia (Lauraceae) was investigated herein. Methods: The n-hexane extract from twigs of N. oppositifolia were subjected to HPLC/HRESIMS and bioactivity-guided fractionation to afford compounds 1 and 2 which were evaluated in vitro against Leishmania (L.) infantum chagasi and NCTC cells. Results: The n-hexane extract displayed activity against L. (L.) infantum chagasi and afforded isolinderanolide E (1) and secosubamolide A (2), which were effective against L. (L.) infantum chagasi promastigotes, with IC50 values of 57.9 and 24.9 mu M, respectively. Compound 2 was effective against amastigotes (IC50 = 10.5 mu M) and displayed moderate mammalian cytotoxicity (CC50 = 42 mu M). The immunomodulatory studies of compound 2 suggested an anti-inflammatory activity, with suppression of IL-6, IL-10, TNF with lack of nitric oxide. Conclusion: This study showed the antileishmanial activity of compounds 1 and 2 isolated from N. oppositifolia. Furthermore, compound 2 demonstrated an antileishmanial activity towards amastigotes associated to an immunomodulatory effect. (AU)