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


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) (2021) Synthesis, antiviral activity, preliminary pharmacokinetics and structural parameters of thiazolide amine salts. FUTURE MEDICINAL CHEMISTRY, 13 (20). pp. 1731-1741.

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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: 18 Jan 2023 21:29
DOI: 10.4155/fmc-2021-0055
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3136375
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