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Bioorg Med Chem Lett ; 40: 127926, 2021 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-33705902

RESUMEN

This work presents the design and synthesis of camphor, fenchone, and norcamphor N-acylhydrazone derivatives as a new class of inhibitors of the Hantaan virus, which causes haemorrhagic fever with renal syndrome (HFRS). A cytopathic model was developed for testing chemotherapeutics against the Hantaan virus, strain 76-118. In addition, a study of the antiviral activity was carried out using a pseudoviral system. It was found that the hit compound possesses significant activity (IC50 = 7.6 ± 2 µM) along with low toxicity (CC50 > 1000 µM). Using molecular docking procedures, the binding with Hantavirus nucleoprotein was evaluated and the correlation between the structure of the synthesised compounds and the antiviral activity was established.


Asunto(s)
Antivirales/farmacología , Canfanos/farmacología , Virus Hantaan/efectos de los fármacos , Hidrazonas/farmacología , Isoindoles/farmacología , Norbornanos/farmacología , Animales , Antivirales/síntesis química , Antivirales/metabolismo , Canfanos/síntesis química , Canfanos/metabolismo , Proteínas de la Cápside/metabolismo , Perros , Diseño de Fármacos , Células HEK293 , Humanos , Hidrazonas/síntesis química , Hidrazonas/metabolismo , Isoindoles/síntesis química , Isoindoles/metabolismo , Células de Riñón Canino Madin Darby , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Norbornanos/síntesis química , Norbornanos/metabolismo , Unión Proteica , Proteínas del Núcleo Viral/metabolismo
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