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Synthesis and Antiviral Activity of Novel Phosphorylated Derivatives of Didanosine Against Newcastle Disease Virus in Chicken
Author(s) -
Suresh Karanam Anandan,
Kadiam Venkata Subbaiah C.,
Basha Thaslim S. K.,
Chamarti Naga Raju,
Kumar Suresh M.,
Wudayagiri Rajendra,
Valluru Lokanatha
Publication year - 2016
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201600038
Subject(s) - in vivo , newcastle disease , virus , superoxide dismutase , in vitro , chemistry , cytopathic effect , catalase , didanosine , lipid peroxidation , antioxidant , pharmacology , virology , biochemistry , biology , viral load , microbiology and biotechnology , antiretroviral therapy
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.