2. Academic Validation
  3. (±)-Licarin A and its semi-synthetic derivatives: In vitro and in silico evaluation of trypanocidal and schistosomicidal activities

(±)-Licarin A and its semi-synthetic derivatives: In vitro and in silico evaluation of trypanocidal and schistosomicidal activities

  • Acta Trop. 2020 Feb;202:105248. doi: 10.1016/j.actatropica.2019.105248.
Vanderlisa Rita Meleti 1,  Viviane Rodrigues Esperandim 1,  Luzio Gabriel Bocalon Flauzino 1,  Anna Helena Prizantelli 1,  Lucas Antônio de Lima Paula 1,  Lizandra Guidi Magalhães 1,  Wilson Roberto Cunha 1,  Rosângela da Silva Laurentiz 2,  Ana Paula da Rocha Pissurno 2,  N P Dhammika Nanayakkara 3,  Ana Carolina Pereira 4,  Jairo Kenupp Bastos 5,  Renato Luis Tâme Parreira 1,  Renato Pereira Orenha 1,  Márcio Luis Andrade E Silva 6
Affiliations

Affiliations

  • 1 Grupo de Pesquisa em Produtos Naturais, Núcleo de Ciências Exatas e Tecnológicas, Universidade de Franca, Avenida Dr. Armando Salles de Oliveira, 201, 14404-600 Franca, SP, Brazil.
  • 2 Departamento de Física e Química, Faculdade de Engenharia, Universidade Estadual Paulista, Ilha Solteira-SP, Brazil.
  • 3 National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, and Department of Pharmacognosy, School of Pharmacy, University of Mississippi, University, MS 38677, USA.
  • 4 Grupo de Pesquisa em Produtos Naturais, Núcleo de Ciências Exatas e Tecnológicas, Universidade de Franca, Avenida Dr. Armando Salles de Oliveira, 201, 14404-600 Franca, SP, Brazil; IF Suldeminas, Avenida Maria da Conceição Santos, 900 - Parque Real, Pouso Alegre - MG, 37550-000, Brazil.
  • 5 Escola de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Avenida do Café s/n, 14040-903 Ribeirão Preto, SP, Brazil.
  • 6 Grupo de Pesquisa em Produtos Naturais, Núcleo de Ciências Exatas e Tecnológicas, Universidade de Franca, Avenida Dr. Armando Salles de Oliveira, 201, 14404-600 Franca, SP, Brazil. Electronic address: marcio.silva@unifran.edu.br.
PMID: 31676458 DOI: 10.1016/j.actatropica.2019.105248
Abstract

This paper reports the synthesis of (±)-licarin A 1, a dihydrobenzofuran neolignan, resultant of an oxidative coupling reaction of isoeugenol and horseradish peroxidase (HRP) Enzyme. Following, three semi-synthetic derivatives from this compound were obtained: benzylated (±)-licarin A 2, methylated (±)-licarin A 3 and acetylated (±)-licarin A 4. After structural elucidation and assignment by Nuclear Magnetic Resonance of 1H, 13C and DEPT, all compounds were evaluated in vitro against Trypomastigote forms of Trypanosoma cruzi (T. cruzi), the etiologic agent of Chagas disease, and Schistosoma mansoni (S. mansoni) worms, the etiologic agent of schistosomiasis. Compound (4) was the most active against S. mansoni adult worms, displaying worm viability reduction at 25 µM and mortality of all worms at 100 and 200 µM within 24 h. Compound 1 was the second most active, showing worm viability reduction at 50 µM and mortality of 25% and 100% of worms in 24h at concentrations of 100 and 200 µM, respectively. In addition, theoretical calculations aiming at finding molecular properties that showed the correlation for schistosomicidal and trypanocidal activities of (±)-licarin A and three of its semi-synthetic derivatives were also performed.

Keywords

(±)-Licarin A; Schistosoma mansoni; Semi-synthetic derivatives; Trypanosoma cruzi; computational study.

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