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
Affiliations
Bruno Casciaro
Department of Biochemical Sciences, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, Italy
Francesca Ghirga
Department of Chemistry and Technology of Drugs, “Department of Excellence 2018–2022”, Sapienza University of Rome, 00185 Rome, Italy
Floriana Cappiello
Department of Biochemical Sciences, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, Italy
Valeria Vergine
Department of Chemistry and Technology of Drugs, “Department of Excellence 2018–2022”, Sapienza University of Rome, 00185 Rome, Italy
Maria Rosa Loffredo
Department of Biochemical Sciences, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, Italy
Silvia Cammarone
Department of Chemistry and Technology of Drugs, “Department of Excellence 2018–2022”, Sapienza University of Rome, 00185 Rome, Italy
Elena Puglisi
Department of Biochemical Sciences, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, Italy
Carola Tortora
Department of Chemistry and Technology of Drugs, “Department of Excellence 2018–2022”, Sapienza University of Rome, 00185 Rome, Italy
Deborah Quaglio
Department of Chemistry and Technology of Drugs, “Department of Excellence 2018–2022”, Sapienza University of Rome, 00185 Rome, Italy
Mattia Mori
Department of Biotechnology, Chemistry and Pharmacy, “Department of Excellence 2018–2022”, University of Siena, 53100 Siena, Italy
Bruno Botta
Department of Chemistry and Technology of Drugs, “Department of Excellence 2018–2022”, Sapienza University of Rome, 00185 Rome, Italy
Maria Luisa Mangoni
Department of Biochemical Sciences, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, Italy
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.
