Phenylpropenoids from Bupleurum fruticosum as Anti-Human Rhinovirus Species A Selective Capsid Binders

  • J Nat Prod. 2017 Oct 27;80(10):2799-2806. doi: 10.1021/acs.jnatprod.7b00648.
Benedetta Fois  1 ,  Giulia Bianco  1 ,  Vijay P Sonar  1 ,  Simona Distinto  1 ,  Elias Maccioni  1 ,  Rita Meleddu  1 ,  Claudia Melis  1 ,  Luisa Marras  2 ,  Raffaello Pompei  2 ,  Costantino Floris  3 ,  Pierluigi Caboni  1 ,  Filippo Cottiglia  1
Affiliations
  • 1. Department of Life and Environmental Sciences, University of Cagliari , Via Ospedale 72, 09124 Cagliari, Italy.
  • 2. Department of Biomedical Sciences, University of Cagliari , 09124 Cagliari, Italy.
  • 3. Dipartimento di Scienze Chimiche, University of Cagliari, Cittadella di Monserrato , 09042 Monserrato, Cagliari, Italy.
PMID: 29039946 DOI: 10.1021/acs.jnatprod.7b00648
Abstract

The dichloromethane extract of the leaves of Bupleurum fruticosum was found to inhibit the replication of human rhinovirus (HRV) serotypes 14 and 39. Bioassay-guided fractionation led to the isolation of seven phenylpropenol derivatives (3-9), two polyacetylenes (1 and 2), and one monoterpene (10). Compounds 1 and 10 were identified as previously undescribed secondary metabolites after extensive 1D and 2D NMR experiments as well as high-resolution mass spectrometry. Compounds 2, 4, and 5 showed a selective inhibition of viral replication against HRV39 serotype, with 2 and 4 being the most active, with EC50 values of 1.8 ± 0.02 and 2.4 ± 0.04 μM. Mechanism of action studies indicated that 4 behaves not only as a capsid binder, interfering with the early phases of virus replication, but also as a late-phase replication inhibitor. Docking experiments were performed to confirm the ability of the Antiviral phenylpropenoids to selectively fit into the hydrophobic pocket of VP1-HRV39.

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