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

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...

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Autores principales: Grecco, Simone S, Costa-Silva, Thais A, Sousa, Fernanda S, Cargnelutti, Stefano B, Umehara, Eric, Mendonça, Poliana S, Tempone, Andre G, Lago, Joao Henrique G
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161432/
https://www.ncbi.nlm.nih.gov/pubmed/30275819
http://dx.doi.org/10.1186/s40409-018-0164-9
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author Grecco, Simone S
Costa-Silva, Thais A
Sousa, Fernanda S
Cargnelutti, Stefano B
Umehara, Eric
Mendonça, Poliana S
Tempone, Andre G
Lago, Joao Henrique G
author_facet Grecco, Simone S
Costa-Silva, Thais A
Sousa, Fernanda S
Cargnelutti, Stefano B
Umehara, Eric
Mendonça, Poliana S
Tempone, Andre G
Lago, Joao Henrique G
author_sort Grecco, Simone S
collection PubMed
description 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 (EC(50) 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 (EC(50) = 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.
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spelling pubmed-61614322018-10-01 Neolignans isolated from twigs of Nectandra leucantha Ness & Mart (Lauraceae) displayed in vitro antileishmanial activity Grecco, Simone S Costa-Silva, Thais A Sousa, Fernanda S Cargnelutti, Stefano B Umehara, Eric Mendonça, Poliana S Tempone, Andre G Lago, Joao Henrique G J Venom Anim Toxins Incl Trop Dis Research 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 (EC(50) 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 (EC(50) = 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. BioMed Central 2018-09-27 /pmc/articles/PMC6161432/ /pubmed/30275819 http://dx.doi.org/10.1186/s40409-018-0164-9 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Grecco, Simone S
Costa-Silva, Thais A
Sousa, Fernanda S
Cargnelutti, Stefano B
Umehara, Eric
Mendonça, Poliana S
Tempone, Andre G
Lago, Joao Henrique G
Neolignans isolated from twigs of Nectandra leucantha Ness & Mart (Lauraceae) displayed in vitro antileishmanial activity
title Neolignans isolated from twigs of Nectandra leucantha Ness & Mart (Lauraceae) displayed in vitro antileishmanial activity
title_full Neolignans isolated from twigs of Nectandra leucantha Ness & Mart (Lauraceae) displayed in vitro antileishmanial activity
title_fullStr Neolignans isolated from twigs of Nectandra leucantha Ness & Mart (Lauraceae) displayed in vitro antileishmanial activity
title_full_unstemmed Neolignans isolated from twigs of Nectandra leucantha Ness & Mart (Lauraceae) displayed in vitro antileishmanial activity
title_short Neolignans isolated from twigs of Nectandra leucantha Ness & Mart (Lauraceae) displayed in vitro antileishmanial activity
title_sort neolignans isolated from twigs of nectandra leucantha ness & mart (lauraceae) displayed in vitro antileishmanial activity
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161432/
https://www.ncbi.nlm.nih.gov/pubmed/30275819
http://dx.doi.org/10.1186/s40409-018-0164-9
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