CFTR corrector; antibacterial; bithiazole; cystic fibrosis; multifunctional; Organic Chemistry; General Pharmacology, Toxicology and Pharmaceutics; Molecular Medicine; Drug Discovery; Biochemistry; Pharmacology
Abstract :
[en] Cystic Fibrosis (CF) is a genetic disease caused by loss-of-function mutations in the CFTR gene, which codes for a defective ion channel. This causes an electrolyte imbalance and results in a spiral of negative effects on multiple organs, most notably the accumulation of thick mucus in the lungs, chronic respiratory tract infections and inflammation leading to pulmonary exacerbation and premature death. Progressive decline of lung function is mainly linked to persistent or recurring infections, mostly caused by bacteria, which require treatments with antibiotics and represent one of the major life-limiting factors in subjects with CF. Treatment of such a complex disease require multiple drugs with a consequent therapeutic burden and complications caused by drug-drug interactions and rapid emergence of bacterial drug resistance. We report herein our recent efforts in developing innovative multifunctional antibiotics specifically tailored to CF by a direct action on bacterial topoisomerases and a potential indirect effect on the pulmonary mucociliary clearance mediated by ΔF508-CFTR correction. The obtained results may pave the way for the development of a simplified therapeutic approach with a single agent acting as multifunctional antibacterial-corrector.
Disciplines :
Microbiology Immunology & infectious disease
Author, co-author :
Martina, Maria Grazia ✱; University of Parma: Universita degli Studi di Parma, Department of Food and Drug, ITALY
Sannio, Filomena ✱; University of Siena: Universita degli Studi di Siena, Dipartimento di Biotecnologie Mediche, ITALY
Crespan, Emmanuele; CNR: Consiglio Nazionale delle Ricerche, Istituto di Genetica Molecolare, IGM-CNR "Luigi Luca Cavalli-Sforza", ITALY
Pavone, Marialaura; University of Parma: Universita degli Studi di Parma, Department of Food and Drug, ITALY
Simoncini, Alice; University of Parma: Universita degli Studi di Parma, Department of Food and Drug, ITALY
Barbieri, Francesca; University of Parma: Universita degli Studi di Parma, Department of Food and Drug, ITALY
Perini, Cecilia; CNR: Consiglio Nazionale delle Ricerche, Istituto di Genetica Molecolare, IGM-CNR "Luigi Luca Cavalli-Sforza", ITALY
Pesce, Emanuela; Istituto Giannina Gaslini Istituto Pediatrico di Ricovero e Cura a Carattere Scientifico: Istituto Giannina Gaslini, U.O.C. Genetica Medica, ITALY
Maga, Giovanni; CNR: Consiglio Nazionale delle Ricerche, Istituto di Genetica Molecolare, IGM-CNR "Luigi Luca Cavalli-Sforza", ITALY
Pedemonte, Nicoletta; Istituto Giannina Gaslini Istituto Pediatrico di Ricovero e Cura a Carattere Scientifico: Istituto Giannina Gaslini, U.O.C. Genetica Medica, ITALY
Docquier, Jean-Denis ; Université de Liège - ULiège > Département des sciences de la vie > Physiologie et génétique bactériennes ; University of Siena: Universita degli Studi di Siena, Dipartimento di Biotecnologie Mediche, ITALY
Radi, Marco; University of Parma, Department of Food and Drug, Viale delle Scienze, 27/A, 43124, Parma, ITALY
✱ These authors have contributed equally to this work.
Language :
English
Title :
Towards Innovative Antibacterial-Correctors for Cystic Fibrosis Targeting the Lung Microbiome with a Multifunctional Effect.
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