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Chemotherapy ; 61(3): 159-66, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26821172

RESUMEN

BACKGROUND: The zoonotic transmission of highly pathogenic avian influenza viruses and the global pandemic of H1N1 influenza in 2009 signified the need for a wider coverage of therapeutic options for the control of influenza. METHODS: An in-house compound library was screened using a cytopathic effect inhibition assay. Selected hits were then tested in vivo and used as a core skeleton for derivative synthesis. RESULTS: The hit compound (BMD-2601505) was effective [50% effective concentration (EC50) of 60-70 µM] in reducing the death rate of cells infected with human influenza A and B viruses as well as avian influenza A virus. Furthermore, BMD-2601505 reduced the weight loss and increased the survival after lethal infection. The compound was further modified to enhance its antiviral potency. Results show that one derivative with bromobenzene moiety was most effective (EC50 of 22-37 µM) against the influenza viruses tested. CONCLUSION: We identified a small benzamide compound exhibiting antiviral activity against influenza viruses. The results warrant further evaluation of antiviral activities against drug-resistant influenza isolates.


Asunto(s)
Antivirales/farmacología , Benzamidas/farmacología , Virus de la Influenza A/efectos de los fármacos , Virus de la Influenza B/efectos de los fármacos , Animales , Antivirales/administración & dosificación , Antivirales/química , Benzamidas/administración & dosificación , Benzamidas/química , Bromobencenos/administración & dosificación , Bromobencenos/química , Bromobencenos/farmacología , Perros , Femenino , Humanos , Gripe Humana/tratamiento farmacológico , Gripe Humana/virología , Células de Riñón Canino Madin Darby , Ratones , Ratones Endogámicos BALB C , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Infecciones por Orthomyxoviridae/virología , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/química , Compuestos de Fenilurea/farmacología , Bibliotecas de Moléculas Pequeñas , Zoonosis/tratamiento farmacológico , Zoonosis/virología
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