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 Ill 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 IC(50)s in the range of 0.14-5.0 mu M. 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.[GRAPHICS].
Stachulski, A.v., Santoro, M.g., Piacentini, S., Belardo, G., La Frazia, S., Pidathala, C., et al. (2018). Second-generation nitazoxanide derivatives: Thiazolides are effective inhibitors of the influenza A virus. FUTURE MEDICINAL CHEMISTRY, 10(8), 851-862 [10.4155/fmc-2017-0217].
Second-generation nitazoxanide derivatives: Thiazolides are effective inhibitors of the influenza A virus
Santoro M. G.;Piacentini S.;BELARDO, GIUSEPPE;La Frazia S.;
2018-04-09
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 Ill 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 IC(50)s in the range of 0.14-5.0 mu M. 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.[GRAPHICS].I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
