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Planta Med 2023; 89(07): 700-708
DOI: 10.1055/a-2009-0732
Biological and Pharmacological Activity
Original Papers

Oxidation Products from the Neolignan Licarin A by Biomimetic Reactions and Assessment of in vivo Acute Toxicity

Juliana Neves de Paula e Souza
1   Núcleo de Pesquisa em Produtos Naturais e Sintéticos (NPPNS), Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
,
Rodrigo Moreira da Silva
1   Núcleo de Pesquisa em Produtos Naturais e Sintéticos (NPPNS), Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
,
Simone Silveira Fortes
2   Departamento de Química, Faculdade de Filosofia Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
,
Anderson Rodrigo Moraes de Oliveira
2   Departamento de Química, Faculdade de Filosofia Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
,
Leandro S. Ferreira 
1   Núcleo de Pesquisa em Produtos Naturais e Sintéticos (NPPNS), Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
3   Departamento de Farmácia, Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN, Brazil
,
Ricardo Vessecchi
2   Departamento de Química, Faculdade de Filosofia Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
,
Norberto Peporine Lopes 
1   Núcleo de Pesquisa em Produtos Naturais e Sintéticos (NPPNS), Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
,
Denise Brentan Silva 
1   Núcleo de Pesquisa em Produtos Naturais e Sintéticos (NPPNS), Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
4   Laboratório de Produtos Naturais e Espectrometria de Massas (LAPNEM), Faculdade de Ciências Farmacêuticas, Alimentos e Nutrição (FACFAN), Universidade Federal de Mato Grosso do Sul, Campo Grande, MS, Brazil
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Abstract

Licarin A, a dihydrobenzofuranic neolignan presents in several medicinal plants and seeds of nutmeg, exhibits strong activity against protozoans responsible for Chagas disease and leishmaniasis. From biomimetic reactions by metalloporphyrin and Jacobsen catalysts, seven products were determined: four isomeric products yielded by epoxidation from licarin A, besides a new product yielded by a vicinal diol, a benzylic aldehyde, and an unsaturated aldehyde in the structure of the licarin A. The incubation with rat and human liver microsomes partially reproduced the biomimetic reactions by the production of the same epoxidized product of m/z 343 [M + H]+. In vivo acute toxicity assays of licarin A suggested liver toxicity based on biomarker enzymatic changes. However, microscopic analysis of tissues sections did not show any tissue damage as indicative of toxicity after 14 days of exposure. New metabolic pathways of the licarin A were identified after in vitro biomimetic oxidation reaction and in vitro metabolism by rat or human liver microsomes.

Key words

Myristica fragrans - Myristicaceae - in vitro metabolism - biomimetic reactions - metalloporphyrins - Jacobsen catalysts - acute toxicity

Supporting Information

    Electronic supplementary information is available for this publication. All the MS, MS/MS, and NMR data from the oxidation products, as well as the biochemical parameters, were determined from acute toxicological essays.

  • Supporting Information


Publication History

Received: 27 July 2022

Accepted: 18 December 2022

Article published online:
08 March 2023

© 2023. Thieme. All rights reserved.

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