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

Stachulski, A. V., Santoro, M. G., Piacentini, S., Belardo, G., La Frazia, S., Pidathala, C., Row, E. C., Berry, N. G., Iqbal, M., Allman, S. A., Semple, J.E., Eklov, B. M., O'Neill, P. M. and Rossignol, J.-F. (2018) Second-generation nitazoxanide derivatives: thiazolides are effective inhibitors of the influenza A virus. Future Medicinal Chemistry, 10 (8). pp. 851-862. ISSN 1756-8919 doi: 10.4155/fmc-2017-0217

Abstract/Summary

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.