Maria Maddalena Cavalluzzi1, Roberta Budriesi2, Maria Antonietta De Salvia3, Laura Quintieri4, Monica Piarulli1, Gualtiero Milani1, Roberta Gualdani5, Matteo Micucci6, Ivan Corazza7, Antonio Rosato1, Maurizio Viale8, Leonardo Caputo4, Carlo Franchini1, Giovanni Lentini1. 1. Department of Pharmacy-Pharmaceutical Sciences, University of Bari Aldo Moro, Bari, Italy. 2. Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Bologna, Italy. 3. Department of Biomedical Sciences and Human Oncology, University of Bari "Aldo Moro", Bari, Italy. 4. Institute of Sciences of Food Production, CNR-ISPA) National Council of Research, Bari, Italy. 5. Laboratory of Cell Physiology, Institute of Neuroscience, Université Catholique de Louvain, 1200, Brussels, Belgium. 6. Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Bologna, Italy. matteo.micucci2@unibo.it. 7. Department of Specialistic, Experimental and Diagnostic Medicine, Alma Mater Studiorum-University of Bologna, Bologna, Italy. 8. IRCCS Azienda Ospedaliera Universitaria San Martino , U.O. Bioterapie, L.go R. Benzi, 10, 16132 , Genoa, Italy.
Abstract
BACKGROUND: Lubeluzole, a neuroprotective anti-ischemic drug, was tested for its ability to act as both antibiotic chemosensitizing and antipropulsive agent for the treatment of infectious diarrhea. METHODS: In the present report, the effect of lubeluzole against antidiarrheal target was tested. The antimicrobial activity towards Gram-positive and Gram-negative bacteria was investigated together with its ability to affect ileum and colon contractility. RESULTS: Concerning the antimicrobial activity, lubeluzole showed synergistic effects when used in combination with minocycline against four common Gram-positive and Gram-negative bacteria (Enterococcus faecalis ATCC 29212, Staphylococcus aureus ATCC 29213, Pseudomonas aeruginosa ATCC 27853, and Escherichia coli ATCC 25922), although relatively high doses of lubeluzole were required. In ex vivo experiments on sections of gut smooth muscles, lubeluzole reduced the intestinal contractility in a dose-dependent manner, with greater effects observed on colon than on ileum, and being more potent than reference compounds otilonium bromide and loperamide. CONCLUSION: All above results identify lubeluzole as a possible starting compound for the development of a novel class of antibacterial adjuvants endowed with spasmolytic activity.
BACKGROUND:Lubeluzole, a neuroprotective anti-ischemic drug, was tested for its ability to act as both antibiotic chemosensitizing and antipropulsive agent for the treatment of infectious diarrhea. METHODS: In the present report, the effect of lubeluzole against antidiarrheal target was tested. The antimicrobial activity towards Gram-positive and Gram-negative bacteria was investigated together with its ability to affect ileum and colon contractility. RESULTS: Concerning the antimicrobial activity, lubeluzole showed synergistic effects when used in combination with minocycline against four common Gram-positive and Gram-negative bacteria (Enterococcus faecalis ATCC 29212, Staphylococcus aureus ATCC 29213, Pseudomonas aeruginosa ATCC 27853, and Escherichia coli ATCC 25922), although relatively high doses of lubeluzole were required. In ex vivo experiments on sections of gut smooth muscles, lubeluzole reduced the intestinal contractility in a dose-dependent manner, with greater effects observed on colon than on ileum, and being more potent than reference compounds otilonium bromide and loperamide. CONCLUSION: All above results identify lubeluzole as a possible starting compound for the development of a novel class of antibacterial adjuvants endowed with spasmolytic activity.
Entities:
Keywords:
Antibiotics; Diarrhoea; Gut contractility; Ion channels; Lubeluzole; Synergism
Authors: Yichao Yang; Kristina M Feye; Zhaohao Shi; Hilary O Pavlidis; Michael Kogut; Amanda J Ashworth; Steven C Ricke Journal: Front Microbiol Date: 2019-07-26 Impact factor: 5.640
Authors: Giovanni Petrillo; Cinzia Tavani; Lara Bianchi; Alice Benzi; Maria Maddalena Cavalluzzi; Lara Salvagno; Laura Quintieri; Annalisa De Palma; Leonardo Caputo; Antonio Rosato; Giovanni Lentini Journal: Molecules Date: 2021-06-25 Impact factor: 4.411