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

Author:

Stachulski Andrew V1ORCID,Rossignol Jean-Francois2,Pate Sophie1,Taujanskas Joshua1,Robertson Craig M1,Aerts Rudi3,Pascal Etienne3,Piacentini Sara4,Frazia Simone La4,Santoro M Gabriella4,O’Neill Paul M1

Affiliation:

1. Department of Chemistry, Robert Robinson Laboratories, University of Liverpool, Liverpool, L69 7ZD, UK

2. Romark Laboratories, LC, Tampa, FL 33609, USA

3. Romark Belgium BVBA, Roosveld 6, Landen, 3400, Belgium

4. Department of Biology, University of Rome Tor Vergata, Rome, 00133, Italy

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.

Funder

Romark Pharmaceuticals

Publisher

Future Science Ltd

Subject

Drug Discovery,Pharmacology,Molecular Medicine

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