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

• Main Authors: Bruno Casciaro (Author), Francesca Ghirga (Author), Floriana Cappiello (Author), Valeria Vergine (Author), Maria Rosa Loffredo (Author), Silvia Cammarone (Author), Elena Puglisi (Author), Carola Tortora (Author), Deborah Quaglio (Author), Mattia Mori (Author), Bruno Botta (Author), Maria Luisa Mangoni (Author)
• Format: Book
• Published: MDPI AG, 2022-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/antibiotics11010084; 2079-6382
• Keywords: antibiotic-resistance; antimicrobial activity; Gram-positive bacteria; biofilm; anthranoid; natural products; Therapeutics. Pharmacology; RM1-950
• Source: Antibiotics, Vol 11, Iss 1, p 84 (2022)

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., <i>Staphylococcus aureus</i> and <i>S. epidermidis</i>) 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.