Identification of substituted [3, 2-a] pyrimidines as selective antiviral agents: molecular modeling study.
A series of novel substituted dihydropyrimidine and 5H-thiazolo [3, 2-a] pyrimidine derivatives were designed and synthesized as a potential target to discover drugs fighting against the viral diseases. The main objective of the present work is to carry out the QSAR studies for all the series of the compounds starting from 4a to 6j to find out their molecular descriptors and predict the biological properties. All of them are showing the best QSAR descriptors, hence chosen for the prediction of anti-viral activity against Newcastle disease virus (NDV). Initially their inhibitory activity was predicted by molecular docking of these compounds against haemaglutinin-neuraminidase (HN) protein using molecular operating environment (MOE) software. Based on the best affinity and highest docking scores 4b, 5b and 6b were assayed in vivo on NDV infected chicks and it was found that there is significant improvement in the survival of the chicks with the treatment (P<0.05). 4b and 6b showed better curative effect than 5b at the dose concentration of 40 mg/kg body weight of chicks. The results from molecular docking study and biological assays can be inferred to consider these molecules as potential antiviral drugs.
Department of Chemistry, Sri Venkateswara University, Tirupati 517502, India.
Kilaru
K
Ravendra Babu
Valasani Koteswara
VK
Rao
Yellapu
Y
Nanda Kumar
Kishore
K
Polireddy
Kadiam
K
Venkata Subbaiah
Matcha
M
Bhaskar
Valluru
V
Lokanatha
Chamarthi
C
Naga Raju
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D002645:Chickens; D056004:Molecular Dynamics Simulation; D009521:Newcastle Disease / Q000188:drug therapy; D009522:Newcastle disease virus / Q000187:drug effects*; D011201:Poultry Diseases / Q000188:drug therapy; D011743:Pyrimidines / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D016019:Survival Analysis
D000998:Antiviral Agents; D011743:Pyrimidines