Neolignans isolated from twigs of Nectandra leucantha Ness & Mart (Lauraceae) displayed in vitro antileishmanial activity

 

Simone S Grecco^1  2, Thais A Costa-Silva¹, Fernanda S Sousa³, Stefano B Cargnelutti³, Eric Umehara¹, Poliana S Mendonça¹, Andre G Tempone⁴, Joao Henrique G Lago

 

1 Center of Natural Sciences and Humanities, Federal University of ABC (UFBC), Avenida dos Estados 5001, Santo Andre, SP 09210-580, Brazil.

2 Biotechnology and Innovation in Health Postgraduate Program, Anhanguera University of São Paulo, São Paulo, SP, Brazil.

3 Institute Environmental, Chemical and Pharmaceutical Sciences, Federal University of São Paulo (UNIFESP), Diadema, SP, Brazil.

4 Center for Parasitology and Mycology, Instituto Adolfo Lutz, São Paulo, SP, Brazil.

 

ABSTRACT

Background:

The therapeutic arsenal for the treatment of Leishmaniasis is limited and includes toxic compounds (antimonials, amphotericin B, pentamidine and miltefosine). Given these aspects, the search for new compounds based on floristic biodiversity is crucial. In the present work, we report the isolation, characterization and antileishmanial activity of six related neolignans (1–6) of bioactive extract from Nectandra leucantha (Lauraceae) twigs.

 

Methods:

Dried and powdered twigs of N. leucantha were exhaustively extracted using n-hexane. The crude extract was dereplicated by HPLC/HRESIMS and subjected to column chromatography to yield pure compounds 1–6. Their chemical structures were identified via NMR and comparison of obtained data with those previously published in the literature. Biological assays of compounds 1–6 and their respective monomers (eugenol and methyleugenol) were performed using promastigote and amastigote forms of Leishmania (L.) infantum.

 

Results:

Dereplication procedures followed by chemical characterization of isolated compounds by NMR enabled the identification of related neolignans 1–6. Neolignans 2, 4 and 6 showed potential against amastigote forms of L. (L.) infantum (EC50 values of 57.9, 67.7 and 13.7 μM, respectively), while compounds 1 and 3 were inactive. As neolignans 2–4 are chemically related, it may be suggested that the presence of the methoxyl group at C4 constitutes an important structural aspect to increase antileishmanial potential against amastigote forms. Compound 6, which consists of a methylated derivative of compound 5 (inactive) showed antileishmanial activity similar to that of the standard drug miltefosine (EC50 =16.9 μM) but with reduced toxicity (SI = 14.6 and 7.2, respectively). Finally, two related monomers, eugenol and methyleugenol, were also tested and did not display activity, suggesting that the formation of dimeric compounds by oxidative coupling is crucial for antiparasitic activity of dimeric compounds 2, 4 and 6

 

Conclusion:

This study highlights compound 6 against L. (L.) infantum amastigotes as a scaffold for future design of new compounds for drug treatment of visceral leishmaniasis.

 

Keywords: Nectandra leucantha; Leishmania (L.)infantum; Antileishmanial activity; Neolignans

 

Received: April 12, 2018.

Accepted: September 17, 2018.

 

Correspondence: joao.lago@ufabc.edu.br

 

Author's contributions

SSG, TACS, FFS, SBC, EU, and PSM performed the research and analyzed data. SSG, FFS, EU, and PSM performed NMR and MS analysis. TACS, AGT and JHGL wrote the manuscript. AGT and JHGL designed the study. All authors read and approved the final manuscript.

 

Competing interests

The authors declare that they have no competing interests.