2. Academic Validation
  3. Tri- and Diterpenoids from Stillingia loranthacea as Inhibitors of Zika Virus Replication

Tri- and Diterpenoids from Stillingia loranthacea as Inhibitors of Zika Virus Replication

  • J Nat Prod. 2019 Oct 25;82(10):2721-2730. doi: 10.1021/acs.jnatprod.9b00251.
Lucas Silva Abreu 1,  Yuri Mangueira do Nascimento 1,  Rafael Dos Santos Costa 2,  Maria Lenise Silva Guedes 3,  Bárbara Nayane Rosário Fernandes Souza 4,  Lindomar José Pena 4,  Vicente Carlos de Oliveira Costa 1,  Marcus Tullius Scotti 1,  Raimundo Braz-Filho 5,  José Maria Barbosa-Filho 1,  Marcelo Sobral da Silva 1,  Eudes da Silva Velozo 2,  Josean Fechine Tavares 1
Affiliations

Affiliations

  • 1 Institute for Research in Pharmaceuticals and Medications , Federal University of Paraíba , João Pessoa 58051-900 , Brazil.
  • 2 Research Laboratory in Materia Medica, School of Pharmacy , Federal University of Bahia , Salvador 40170-290 , Brazil.
  • 3 Institute of Biology , Federal University of Bahia , Salvador 40110-060 , Brazil.
  • 4 Department of Virology , Oswaldo Cruz Foundation (Fiocruz) , Recife 50740-465 , Brazil.
  • 5 Department of Chemistry, Institute of Chemistry , Federal Rural University of Rio de Janeiro , Seropédica 23890-000 , Brazil.
PMID: 31599155 DOI: 10.1021/acs.jnatprod.9b00251
Abstract

This study represents the first phytochemical analysis of Stillingia loranthacea (S. loranthacea) and describes new Terpenoids obtained from the root bark of this species. The fractionation of the hexane extract from the root bark led to the isolation of two new 28-nor-taraxarenes derivatives, loranthones A and B (1 and 2), four new tigliane diterpenes (5-8), three known tigliane diterpenes (9-11), and three known flexibilene diterpenes, tonantzitlolones A-C (12-14). The investigation of these compounds and the use of a molecular networking-based prioritization approach afforded two Other new 28-nor-taraxarenes, loranthones C and D (3 and 4). The cytotoxicity of compounds 1, 2, and 5-14 was evaluated against Vero cells, and their 20% cytotoxic concentration (CC20) values varied from 8.7 to 328 μM; Antiviral activity was tested against an epidemic Zika virus (ZIKV) strain circulating in Brazil. Six out of 12 compounds (2, 5, 9-11, and 14) exhibited significant Antiviral effects against ZIKV. Specifically, compounds 2 and 5 offered the most promise as lead compounds as they had a 1.7 and 1.8 log10 TCID50/mL reduction in ZIKV replication, respectively. Together, the present findings have identified S. loranthacea Terpenoids as potent anti-ZIKV inhibitors and pave the way to the development of possible new treatments against this devastating pathogen.

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