Modelling And Syntheses Of Vanillin Derivatives Targeting Influenza Virus Neuraminidase
Loading...
Date
2016-11
Authors
Asaruddin, Mohd Razip
Journal Title
Journal ISSN
Volume Title
Publisher
Universiti Sains Malaysia
Abstract
Influenza remains a serious global threat. To date, zanamivir and oseltamivir
used as NA inhibitors were reported to be resistant to influenza virus. Therefore, new
and effective NA inhibitors must be discovered. In this study, pharmacophore
modelling approach was used to search for NA inhibitors with new scaffold. Two
computer softwares such as Discovery Studio 2.5 and LigandScout 3.1 was utilized.
Through the softwares, the pharmacophore modelling approaches was generated.
Ligand-based and structure-based pharmacophore modelling approaches will
complement each other. Ligand-based pharmacophore modelling approach is based
on common features functional groups. This approach utilize training set, a set of
established compounds used as NA inhibitors. The training set was selected from
chemically diverse NA inhibitors. The other approach is structure-based
pharmacophore modelling. Through this approach, the interactions between NA
inhibitors in active site can be observed. In this study, 2HU0 (from pdb) was used as
protein target incorporated oseltamivir carboxylate. Compound which shows greater
alignment score towards oseltamivir carboxylate will potentially enhance NA
inhibition activity. As a results, both pharmacophore modelling approaches,
potentially NA inhibitors could be predicted. Compounds which pass through this
step was further to be evaluated for biological evaluation ie MUNANA assay (NA
inhibition activity). From the three thousand compounds screened, about fourty
seven compounds potentially as NA inhibitors was identified. Some compounds
among the fourty seven compounds such as betalain showed very good fit value
indicating potential NA inhibitors but these compounds was found to be unstable
(decomposed) upon extraction and isolation process.
Description
Keywords
Modelling and syntheses of vanillin derivatives , targeting influenza virus neuraminidase