FFC#16/2015

Development of metallo-enzyme inhibitors to overcome P. aeruginosa antibiotic-resistance in cystic fibrosis patients

FFC#16/2015

Development of metallo-enzyme inhibitors to overcome P. aeruginosa antibiotic-resistance in cystic fibrosis patients

PRINCIPAL INVESTIGATOR

Sandra Gemma (Dipartimento di Biotecnologia, Chimica e Farmacia – Università di Siena)

Partner

Jean-Denis Docquier (Dip. di Biotecnologia Medica – Università di Siena)

RESEARCHERS

10

CATEGORY

AREA 3 Bronchopulmonary infection

DURATION

1 year

GOAL

€ 30.000 €

RESULTS

Novel classes of potential MBL inhibitors were investigated. A concerted effort of computational and synthetic chemistry was carried out and new compounds were identified. Researchers studied their structure-activity relationship and selected drug-like properties, such as solubility, chemical stability and toxicity. The initial hit NF1810 was optimized providing a broad spectrum inhibitor. However, specific solubility and toxicity issues need to be solved in order to identify inhibitors suitable for in vivo evaluation. No MBL inhibitors have been approved in therapy today. Novel hits were identified in this project and their further optimization could lead to the selection of preclinical candidates to establish the proof-of-concept for novel combination therapies (antibiotics plus MBL inhibitors) for the treatment of lung infections in CF patients.

OTHER RESULTS

FFC #3/2024

Two molecules are effective in activating Heat Shock Proteins and enhancing the action of CFTR correctors with the F508del mutation in vitro.

FFC#5/2024

Some peptide nucleic acids (PNAs) re-sensitise Pseudomonas aeruginosa to the antibiotic meropenem in vitro and reduce its virulence.

FFC#1/2023

Tezacaftor, one of the components of Kaftrio, induces an accumulation of dihydroceramides both in vitro and in vivo in animal models