Abstract
EtOH extracts from the leaves and twigs of Nectandra oppositifolia Nees & Mart. shown activity against amastigote forms of Trypanosoma cruzi. These extracts were subjected to successive liquid-liquid partitioning to afford bioactive CH2Cl2 fractions. UHPLC-TOF-HRMS/MS and molecular networking were used to obtain an overview of the phytochemical composition of these active fractions. Aiming to isolate the active compounds, both CH2Cl2 fractions were subjected to fractionation using medium pressure chromatography combined with semi-preparative HPLC-UV. Using this approach, twelve compounds (1-12) were isolated and identified by NMR and HRMS analysis. Several isolated compounds displayed activity against the amastigote forms of T. cruzi, especially ethyl protocatechuate (7) with EC50 value of 18.1 μM, similar to positive control benznidazole (18.7 μM). Considering the potential of compound 7, protocatechuic acid and its respective methyl (7a), n-propyl (7b), n-butyl (7c), n-pentyl (7d), and n-hexyl (7e) esters were tested. Regarding antitrypanosomal activity, protocatechuic acid and compound 7a were inactive, while 7b-7e exhibited EC50 values from 20.4 to 11.7 μM, without cytotoxicity to mammalian cells. These results suggest that lipophilicity and molecular complexity play an important role in the activity while efficiency analysis indicates that the natural compound 7 is a promising prototype for further modifications to obtain compounds effective against the intracellular forms of T. cruzi.
Highlights
The genus Nectandra is composed of more than 120 species with a wide diversity in the Brazilian Atlantic Forest [1]
The antitrypanosomal neolignan licarin A was isolated from the n-hexane extract of Nectandra oppositifolia Nees & Mart. leaves and, considering its interesting activity against the amastigote forms of Trypanosoma cruzi, a series of semisynthetic derivatives were prepared for a structure-activity relationship (SAR) study [6]
Three related butenolides were isolated from the n-hexane extract of N. oppositifolia twigs, which displayed anti-Trypanosoma cruzi activity [7] and immunomodulatory effect against Leishmania infantum [8]
Summary
The genus Nectandra is composed of more than 120 species with a wide diversity in the Brazilian Atlantic Forest [1]. As part of our continuous study aiming to discover antitrypanosomal natural products from plant biodiversity, our group has reported several promising compounds from these species. The antitrypanosomal neolignan licarin A was isolated from the n-hexane extract of Nectandra oppositifolia Nees & Mart. Three related butenolides were isolated from the n-hexane extract of N. oppositifolia twigs, which displayed anti-Trypanosoma cruzi activity [7] and immunomodulatory effect against Leishmania infantum [8]. These trypanosomatids are etiological agents of Chagas disease and leishmaniasis, respectively [9]
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