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.; Iqbal, Mazhar; Allman, Sarah A.; Semple, J Edward; Eklov, Brian M.; O'Neill, Paul M. and Rossignol, Jean-Francois (2018). Second-generation nitazoxanide derivatives: thiazolides are effective inhibitors of the influenza A virus. Future Medicinal Chemistry, 10(8) pp. 851–862.

DOI: https://doi.org/10.4155/fmc-2017-0217

Abstract

Aim: 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. Results: 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 IC50s 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. Conclusion: 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.

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