Second-generation nitazoxanide derivatives: thiazolides are effective inhibitors of the influenza A virus


Stachulski, Andrew V, Santoro, M Gabriella, Piacentini, Sara, Belardo, Giuseppe, La Frazia, Simone, Pidathala, Chandrakala, Row, Eleanor C, Berry, Neil G ORCID: 0000-0003-1928-0738, Iqbal, Mazhar, Allman, Sarah A et al (show 4 more authors) (2018) Second-generation nitazoxanide derivatives: thiazolides are effective inhibitors of the influenza A virus. FUTURE MEDICINAL CHEMISTRY, 10 (8). pp. 851-862.

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Abstract

<h4>Aim</h4>The only small molecule drugs currently available for treatment of influenza A virus (IAV) are M2 ion channel blockers and sialidase inhibitors. The prototype thiazolide, nitazoxanide, has successfully completed Phase III clinical trials against acute uncomplicated influenza.<h4>Results</h4>We report the activity of seventeen thiazolide analogs against A/PuertoRico/8/1934(H1N1), a laboratory-adapted strain of the H1N1 subtype of IAV, in a cell culture-based assay. A total of eight analogs showed IC<sub>50</sub>s in the range of 0.14-5.0 μM. Additionally a quantitative structure-property relationship study showed high correlation between experimental and predicted activity based on a molecular descriptor set.<h4>Conclusion</h4>A range of thiazolides show useful activity against an H1N1 strain of IAV. Further evaluation of these molecules as potential new small molecule therapies is justified.

Item Type: Article
Uncontrolled Keywords: antiviral drugs, computational chemistry, drug discovery, molecular modeling
Depositing User: Symplectic Admin
Date Deposited: 04 Jun 2018 14:57
Last Modified: 19 Jan 2023 01:33
DOI: 10.4155/fmc-2017-0217
Open Access URL: http://doi.org/10.4155/fmc-2017-0217
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3021888
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