1. Synthesis, antiviral activity, preliminary pharmacokinetics and structural parameters of thiazolide amine salts
- Author
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Jean-Francois Rossignol, M. Gabriella Santoro, Simone La Frazia, Paul M. O'Neill, Sara Piacentini, Andrew V. Stachulski, Sophie L Pate, Rudi Aerts, Etienne Pascal, Joshua Taujanskas, and Craig M. Robertson
- Subjects
Cell Survival ,Metabolite ,Microbial Sensitivity Tests ,Pharmacology ,Antiviral Agents ,Settore MED/07 ,chemistry.chemical_compound ,Pharmacokinetics ,Drug Discovery ,medicine ,Humans ,Amines ,Cells, Cultured ,Molecular Structure ,Nitazoxanide ,antiviral ,Thiazoles ,chemistry ,A549 Cells ,Influenza A virus ,Molecular Medicine ,Salts ,Amine gas treating ,thiazolides ,medicine.drug - Abstract
Background: The thiazolides, typified by nitazoxanide, are an important class of anti-infective agents. A significant problem with nitazoxanide and its active circulating metabolite tizoxanide is their poor solubility. Results: We report the preparation and evaluation of a series of amine salts of tizoxanide and the corresponding 5-Cl thiazolide. These salts demonstrated improved aqueous solubility and absorption, as shown by physicochemical and in vivo measurements. They combine antiviral activity against influenza A virus with excellent cell safety indices. We also report the x-ray crystal structural data of the ethanolamine salt. Conclusion: The ethanol salt of thiazolide retains the activity of the parent together with an improved cell safety index, making it a good candidate for further evaluation.
- Published
- 2021