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Arch Pharm (Weinheim) ; 349(6): 442-55, 2016 Jun.
Article de Anglais | MEDLINE | ID: mdl-27128998

RÉSUMÉ

A series of novel phosphorylated derivatives of didanosine were designed and docking studies were performed with a fusion protein of the Newcastle disease virus (NDV), to develop antiviral compounds against NDV. Based on the docking scores and binding affinities, three derivatives were selected. These compounds were synthesized and characterized by IR, (1) H, (13) C, (31) P, and CHN analysis and mass spectra. They were assessed for their in vitro antiviral activity in DF-1 cells; DDI-10 showed better antiviral activity as evidenced by significant reduction in plaque formation and cytopathic effects. DDI-10 was further evaluated in NDV-infected chicken; the survival rates and antioxidant enzyme levels in brain, liver, and lung tissues were estimated. Superoxide dismutase and catalase were significantly raised, and lipid peroxidation and HA titer levels were decreased upon treatment with 1.5 mg/kg body weight of DDI-10 than with 3 mg/kg body weight of DDI. Further histopathological alterations in NDV-infected tissues were restored in chicken treated with DDI-10. Thus, based on the results from in silico, in vitro, and in vivo assays, the novel phosphorylated DDI-10 might be considered as potent antiviral compound for NDV infection in chicken.


Sujet(s)
Antiviraux/synthèse chimique , Antiviraux/pharmacologie , Poulets/virologie , Didéoxyinosine/analogues et dérivés , Didéoxyinosine/pharmacologie , Maladie de Newcastle/virologie , Virus de la maladie de Newcastle/effets des médicaments et des substances chimiques , Animaux , Antiviraux/composition chimique , Antiviraux/usage thérapeutique , Encéphale/métabolisme , Catalase/métabolisme , Cellules cultivées , Didéoxyinosine/composition chimique , Didéoxyinosine/usage thérapeutique , Hémagglutination/effets des médicaments et des substances chimiques , Peroxydation lipidique/effets des médicaments et des substances chimiques , Foie/métabolisme , Poumon/métabolisme , Simulation de docking moléculaire , Maladie de Newcastle/traitement médicamenteux , Phosphorylation , Maladies de la volaille/traitement médicamenteux , Maladies de la volaille/virologie , Relation quantitative structure-activité , Superoxide dismutase/métabolisme , Analyse de survie
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