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

Author(s):Show less -

Meleti, Vanderlisa Rita ^[1] ; Esperandim, Viviane Rodrigues ^[1] ; Bocalon Flauzino, Luzio Gabriel ^[1] ; Prizantelli, Anna Helena ^[1] ; de Lima Paula, Lucas Antonio ^[1] ; Magalhaes, Lizandra Guidi ^[1] ; Cunha, Wilson Roberto ^[1] ; Laurentiz, Rosangela da Silva ^[2] ; da Rocha Pissurno, Ana Paula ^[2] ; Dhammika Nanayakkara, N. P. ^{[3, 4]} ; Pereira, Ana Carolina ^{[1, 5]} ; Bastos, Jairo Kenupp ^[6] ; Tame Parreira, Renato Luis ^[1] ; Orenha, Renato Pereira ^[1] ; Andrade e Silva, Marcio Luis ^[1]

Affiliation

^[1] Univ Franca, Nucleo Ciencias Exatas & Tecnol, Grp Pesquisa Produtos Nat, Ave Dr Armando Salles de Oliveira 201, BR-14404600 Franca, SP - Brazil

^[2] Univ Estadual Paulista, Fac Engn, Dept Fis & Quim, Ilha Solteira, SP - Brazil

^[3] Univ Mississippi, Sch Pharm, Dept Pharmacognosy, University, MS 38677 - USA

^[4] Univ Mississippi, Sch Pharm, Res Inst Pharmaceut Sci, Natl Ctr Nat Prod Res, University, MS 38677 - USA

^[5] IF Suldeminas, Ave Maria da Conceicao Santos, 900 Parque Real, BR-37550000 Pouso Alegre, MG - Brazil

^[6] Univ Sao Paulo, Escola Ciencias Farmaceut Ribeirao Preto, Ave Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Acta Tropica; v. 202, FEB 2020.
• Web of Science Citations: 0

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 H-1, C-13 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 mu M and mortality of all worms at 100 and 200 mu M within 24 h. Compound 1 was the second most active, showing worm viability reduction at 50 mu M and mortality of 25% and 100% of worms in 24h at concentrations of 100 and 200 mu M, 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. (AU)

• FAPESP's process: 11/07623-8 - The use of quantum-mechanical methods to study the bonds and chemical interactions in self-organizing systems with applications in catalysis, medicinal chemistry, electrochromism, energy storage and conversion
• Grantee: Renato Luis Tame Parreira
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 09/05049-2 - Development of polymeric nanaparticles and biodegradable systems containing lignans and evaluation its Chagas disease and schistosomiasis activities in vitro and in vivo
• Grantee: Márcio Luís Andrade e Silva
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/24856-2 - The Mechanism of the Substitution Reaction of the Ligand Nitrosyl by Aqua in Ruthenium Coordination Compounds
• Grantee: Renato Pereira Orenha
• Support Opportunities: Scholarships in Brazil - Post-Doctoral