Synthesis, antiviral activity, preliminary pharmacokinetics and structural parameters of thiazolide amine salts

Collapse authors list.
Stachulski, Andrew V, Rossignol, Jean-Francois, Pate, Sophie, Taujanskas, Joshua, Robertson, Craig M ORCID: 0000-0002-4789-7607, Aerts, Rudi, Pascal, Etienne, Piacentini, Sara, Frazia, Simone La, Santoro, M Gabriella et al (show 1 more authors) and O'Neill, Paul M ORCID: 0000-0003-4338-0317 (2021) Synthesis, antiviral activity, preliminary pharmacokinetics and structural parameters of thiazolide amine salts. FUTURE MEDICINAL CHEMISTRY, 13 (20). pp. 1731-1741. ISSN 1756-8919, 1756-8927

Text Thiaz_Salts_v12a_FMC.docx - Author Accepted Manuscript Download (418kB)

Abstract

<b>Background:</b> 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. <b>Results:</b> 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 <i>in vivo</i> 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. <b>Conclusion:</b> 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.

Item Type:	Article
Uncontrolled Keywords:	amine salts, antiviral, pharmacokinetics, thiazolides, x-ray structure
Divisions:	Faculty of Science and Engineering > School of Physical Sciences
Depositing User:	Symplectic Admin
Date Deposited:	09 Sep 2021 08:20
Last Modified:	07 Dec 2024 21:25
DOI:	10.4155/fmc-2021-0055
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3136375