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].
9-apr-2018
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICA
English
Con Impact Factor ISI
antiviral drugs; computational chemistry; drug discovery; molecular modeling
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].
Stachulski, Av; Santoro, Mg; Piacentini, S; Belardo, G; La Frazia, S; Pidathala, C; Row, Ec; Berry, Ng; Iqbal, M; Allman, Sa; Edward Semple, J; Eklov, Bm; O'Neill, Pm; Rossignol, J-
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/201246
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