Antibiotics (Jan 2022)

The Triprenylated Anthranoid Ferruginin A, a Promising Scaffold for the Development of Novel Antibiotics against Gram-Positive Bacteria

  • Bruno Casciaro,
  • Francesca Ghirga,
  • Floriana Cappiello,
  • Valeria Vergine,
  • Maria Rosa Loffredo,
  • Silvia Cammarone,
  • Elena Puglisi,
  • Carola Tortora,
  • Deborah Quaglio,
  • Mattia Mori,
  • Bruno Botta,
  • Maria Luisa Mangoni

DOI
https://doi.org/10.3390/antibiotics11010084
Journal volume & issue
Vol. 11, no. 1
p. 84

Abstract

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In today’s post-antibiotic era, the search for new antimicrobial compounds is of major importance and nature represents one of the primary sources of bioactive molecules. In this work, through a cheminformatics approach, we clustered an in-house library of natural products and their derivatives based on a combination of fingerprints and substructure search. We identified the prenylated emodine-type anthranoid ferruginin A as a novel antimicrobial compound. We tested its ability to inhibit and kill a panel of Gram-positive and Gram-negative bacteria, and compared its activity with that of two analogues, vismione B and ferruanthrone. Furthermore, the capability of these three anthranoids to disrupt staphylococcal biofilm was investigated, as well as their effect on the viability of human keratinocytes. Ferruginin A showed a potent activity against both the planktonic and biofilm forms of Gram-positive bacteria (i.e., Staphylococcus aureus and S. epidermidis) and had the best therapeutic index compared to vismione B and ferruanthrone. In conclusion, ferruginin A represents a promising scaffold for the further development of valuable antimicrobial agents.

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