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Novel [1,3,4]Thiadiazole[3,2-a]pyrimidin-5-ones as Promising Biofilm Dispersal Agents against Relevant Gram-Positive and Gram-Negative Pathogens

Authors :
Daniela Carbone
Camilla Pecoraro
Fabio ScianĂ²
Valentina Catania
Domenico Schillaci
Barbara Manachini
Stella Cascioferro
Patrizia Diana
Barbara Parrino
Source :
Marine Drugs, Vol 22, Iss 3, p 133 (2024)
Publication Year :
2024
Publisher :
MDPI AG, 2024.

Abstract

Biofilm-associated infections pose significant challenges in healthcare settings due to their resistance to conventional antimicrobial therapies. In the last decade, the marine environment has been a precious source of bioactive molecules, including numerous derivatives with antibiofilm activity. In this study, we reported the synthesis and the biological evaluation of a new series of twenty-two thiadiazopyrimidinone derivatives obtained by using a hybridization approach combining relevant chemical features of two important classes of marine compounds: nortopsentin analogues and Essramycin derivatives. The synthesized compounds were in vitro tested for their ability to inhibit biofilm formation and to disrupt mature biofilm in various bacterial strains. Among the tested compounds, derivative 8j exhibited remarkable dispersal activity against preformed biofilms of relevant Gram-positive and Gram-negative pathogens, as well as towards the fungus Candida albicans, showing BIC50 values ranging from 17 to 40 µg/mL. Furthermore, compound 8j was in vivo assayed for its toxicity and the anti-infective effect in a Galleria mellonella model. The results revealed a promising combination of anti-infective properties and a favorable toxicity profile for the treatment of severe chronic biofilm-mediated infections.

Details

Language :
English
ISSN :
16603397
Volume :
22
Issue :
3
Database :
Directory of Open Access Journals
Journal :
Marine Drugs
Publication Type :
Academic Journal
Accession number :
edsdoj.559fdbc9482aa8bc74a8f263d6a3
Document Type :
article
Full Text :
https://doi.org/10.3390/md22030133