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

• Published in: Acta tropica 2020-02, Vol.202, p.105248-105248, Article 105248
• Main Authors: Meleti, Vanderlisa Rita, Esperandim, Viviane Rodrigues, Flauzino, Luzio Gabriel Bocalon, Prizantelli, Anna Helena, Paula, Lucas Antônio de Lima, Magalhães, Lizandra Guidi, Cunha, Wilson Roberto, Laurentiz, Rosângela da Silva, Pissurno, Ana Paula da Rocha, Nanayakkara, N.P. Dhammika, Pereira, Ana Carolina, Bastos, Jairo Kenupp, Parreira, Renato Luis Tâme, Orenha, Renato Pereira, e Silva, Márcio Luis Andrade
• Format: Article
• Language: English
• Subjects: (±)-Licarin A; Animals; Chagas Disease - drug therapy; computational study; Computer Simulation; Lignans - chemical synthesis; Lignans - pharmacology; Lignans - therapeutic use; Schistosoma mansoni; Schistosoma mansoni - drug effects; Schistosomiasis - drug therapy; Schistosomicides - chemical synthesis; Schistosomicides - pharmacology; Semi-synthetic derivatives; Trypanocidal Agents - chemical synthesis; Trypanocidal Agents - pharmacology; Trypanosoma cruzi; Trypanosoma cruzi - drug effects
• ISSN: 0001-706X; 1873-6254
• DOI: 10.1016/j.actatropica.2019.105248

•This paper reports the synthesis of (±)-licarin A.•Three semi-synthetic derivatives of (±)-licarin A also were prepared.•The compounds were evaluated against Trypanosoma cruzi, and Schistosoma mansoni.•Licarin A was the most active against T. cruzi.•The acetylated derivative was the most active against S. mansoni.•Computational study 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. [Display omitted]