Antiparasitic neolignans from leaves of Nectandra leucantha

Abstract

Previous studies performed with Nectandra leucantha Ness & Mart (Lauraceae) afforded three neolignans with significant activity against Leishmania donovani [3]. In continuation of our studies with this specie, the n-hexane and MeOH extracts from leaves displayed activity against Leishmania (L.) infantum and Trypanosoma cruzi. Using a bioactivity guided fractionation, were obtained five neolignans: dehydrodieugenol (1), dehydrodieugenol B (2), 1,2-dimethoxy-6-[2'-methoxy-4'-(8'-propenyl)phenoxy]-4-(8-propenyl)benzene (3), (R)-1-hydroxy-2-methoxy-6-[2'-methoxy-4'-(8'-propenyl)phenoxy]-4-(7-hydroxy-8-propenyl)benzene (4), and (S)-1,2-dimethoxy-6-[2'-methoxy-4'-(8'-propenyl)phenoxy]-4-(7-hydroxy-8-propenyl)benzene (5), including two new metabolites (4 and 5). The structures of isolated compounds were determined by analysis of NMR, UV, IR, HRESIMS, as well as CD spectral data. The in vitro antiparasitic activity of the isolated compounds against L. (L.) infantum and T. cruzi as well as mammalian cytotoxicity was evaluated. Compounds 2 and 3 were effective against the intracellular amastigotes of L. (L.) infantum (IC50 values of 85.5 and 19.7 µM, respectively) while compound 4 displayed activity against trypomastigote forms of T. cruzi (IC50 value of 20.5 µM). The mammalian cytotoxicity (CC50) was evaluated against peritoneal macrophages. Compounds 1, 3 – 5 were not toxic up to 200 µM, whereas compound 2 demonstrated a CC50 value of 154.2 µM. Therefore, considering the effective antiparasitic activity of the neolignans 3 and 4, the obtained results suggest these compounds as candidates for future experimental pre-clinical assays against visceral leishmaniasis and Chagas disease.