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Discovery of New Hits as Antitrypanosomal Agents by In Silico and In Vitro Assays Using Neolignan-Inspired Natural Products from Nectandra leucantha
In the present study, the phytochemical study of the n-hexane extract from flowers of Nectandra leucantha (Lauraceae) afforded six known neolignans (1–6) as well as one new metabolite (7), which were characterized by analysis of NMR, IR, UV, and ESI-HRMS data. The new compound 7 exhibited potent act...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306904/ https://www.ncbi.nlm.nih.gov/pubmed/34299391 http://dx.doi.org/10.3390/molecules26144116 |
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author | Araujo, Sheila C. Sousa, Fernanda S. Costa-Silva, Thais A. Tempone, Andre G. Lago, João Henrique G. Honorio, Kathia M. |
author_facet | Araujo, Sheila C. Sousa, Fernanda S. Costa-Silva, Thais A. Tempone, Andre G. Lago, João Henrique G. Honorio, Kathia M. |
author_sort | Araujo, Sheila C. |
collection | PubMed |
description | In the present study, the phytochemical study of the n-hexane extract from flowers of Nectandra leucantha (Lauraceae) afforded six known neolignans (1–6) as well as one new metabolite (7), which were characterized by analysis of NMR, IR, UV, and ESI-HRMS data. The new compound 7 exhibited potent activity against the clinically relevant intracellular forms of T. cruzi (amastigotes), with an IC(50) value of 4.3 μM and no observed mammalian cytotoxicity in fibroblasts (CC(50) > 200 μM). Based on the results obtained and our previous antitrypanosomal data of 50 natural and semi-synthetic related neolignans, 2D and 3D molecular modeling techniques were employed to help the design of new neolignan-based compounds with higher activity. The results obtained from the models were important to understand the main structural features related to the biological response of the neolignans and to aid in the design of new neolignan-based compounds with better biological activity. Therefore, the results acquired from phytochemical, biological, and in silico studies showed that the integration of experimental and computational techniques consists of a powerful tool for the discovery of new prototypes for development of new drugs to treat CD. |
format | Online Article Text |
id | pubmed-8306904 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-83069042021-07-25 Discovery of New Hits as Antitrypanosomal Agents by In Silico and In Vitro Assays Using Neolignan-Inspired Natural Products from Nectandra leucantha Araujo, Sheila C. Sousa, Fernanda S. Costa-Silva, Thais A. Tempone, Andre G. Lago, João Henrique G. Honorio, Kathia M. Molecules Article In the present study, the phytochemical study of the n-hexane extract from flowers of Nectandra leucantha (Lauraceae) afforded six known neolignans (1–6) as well as one new metabolite (7), which were characterized by analysis of NMR, IR, UV, and ESI-HRMS data. The new compound 7 exhibited potent activity against the clinically relevant intracellular forms of T. cruzi (amastigotes), with an IC(50) value of 4.3 μM and no observed mammalian cytotoxicity in fibroblasts (CC(50) > 200 μM). Based on the results obtained and our previous antitrypanosomal data of 50 natural and semi-synthetic related neolignans, 2D and 3D molecular modeling techniques were employed to help the design of new neolignan-based compounds with higher activity. The results obtained from the models were important to understand the main structural features related to the biological response of the neolignans and to aid in the design of new neolignan-based compounds with better biological activity. Therefore, the results acquired from phytochemical, biological, and in silico studies showed that the integration of experimental and computational techniques consists of a powerful tool for the discovery of new prototypes for development of new drugs to treat CD. MDPI 2021-07-06 /pmc/articles/PMC8306904/ /pubmed/34299391 http://dx.doi.org/10.3390/molecules26144116 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Araujo, Sheila C. Sousa, Fernanda S. Costa-Silva, Thais A. Tempone, Andre G. Lago, João Henrique G. Honorio, Kathia M. Discovery of New Hits as Antitrypanosomal Agents by In Silico and In Vitro Assays Using Neolignan-Inspired Natural Products from Nectandra leucantha |
title | Discovery of New Hits as Antitrypanosomal Agents by In Silico and In Vitro Assays Using Neolignan-Inspired Natural Products from Nectandra leucantha |
title_full | Discovery of New Hits as Antitrypanosomal Agents by In Silico and In Vitro Assays Using Neolignan-Inspired Natural Products from Nectandra leucantha |
title_fullStr | Discovery of New Hits as Antitrypanosomal Agents by In Silico and In Vitro Assays Using Neolignan-Inspired Natural Products from Nectandra leucantha |
title_full_unstemmed | Discovery of New Hits as Antitrypanosomal Agents by In Silico and In Vitro Assays Using Neolignan-Inspired Natural Products from Nectandra leucantha |
title_short | Discovery of New Hits as Antitrypanosomal Agents by In Silico and In Vitro Assays Using Neolignan-Inspired Natural Products from Nectandra leucantha |
title_sort | discovery of new hits as antitrypanosomal agents by in silico and in vitro assays using neolignan-inspired natural products from nectandra leucantha |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306904/ https://www.ncbi.nlm.nih.gov/pubmed/34299391 http://dx.doi.org/10.3390/molecules26144116 |
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