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

Antibiotics

Bruno Casciaro¹  Elena Puglisi¹  Maria Luisa Mangoni¹  Floriana Cappiello¹  Maria Rosa Loffredo¹  Mattia Mori²  Francesca Ghirga³  Carola Tortora³  Bruno Botta³  Valeria Vergine³  Silvia Cammarone³  Deborah Quaglio³ 

[1] Department of Biochemical Sciences, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, Italy;Department of Biotechnology, Chemistry and Pharmacy, “Department of Excellence 2018–2022”, University of Siena, 53100 Siena, Italy;Department of Chemistry and Technology of Drugs, “Department of Excellence 2018–2022”, Sapienza University of Rome, 00185 Rome, Italy;

关键词: antibiotic-resistance;    antimicrobial activity;    Gram-positive bacteria;    biofilm;    anthranoid;    natural products;   

DOI  :  10.3390/antibiotics11010084

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown