Volume 14, Issue 33, January - June, 2020

Virtual screening of few novel Sulindac derivatives as multi-targeted agents

Arka Das^♦, Sudipta Nandi, Kingshuk Das, Subhasis Banerjee

Department of Pharmaceutical Chemistry, Gupta College of Technological Sciences, Ashram More, Asansol-713301, West Bengal, India

^♦Corresponding author
Department of Pharmaceutical Chemistry, Gupta College of Technological Sciences, Ashram More, Asansol-713301, West Bengal, India; Email: arkadas5196@gmail.com; Tel: 9641003899.

ABSTRACT

The immense contribution of structure based drug design in the field of drug discovery is noteworthy. Molecular docking methodology has drawn considerable attention in it. Observing multiple affinities in a single chemical entity is one of the biggest challenges in modern drug discovery. One of the drug with this feature is Sulindac. Owing to its affinity towards multiple targets, PPAR-γ, β-secretase and COX-2, several derivatives were designed and subsequently docked to develop binding mode within the active site of the respective targets. The comparison in the binding energy was made considering the cocrystal associated with each target. All the docked compounds were evaluated for their drug likeliness. Parameters, like binding energies and distance between the conformer and active site residues were considered. Majority of compounds exhibited significant affinity towards the enzyme COX-2. However, for PPAR-γ, promising interaction was noticed for several compounds, including AKS 10, AKS 27, AKS33. Highest affinity was found in AKS 33 and AKS 34 towards β-secretase. The outcome of the in-silico approach leaves a great scope for optimization as most of the Sulindac derivatives exhibit considerable affinity towards the respective targets, hence requires further elaboration towards synthesis and biological evaluation

Keywords: PPAR-γ, β-secretase, COX-2, Molecular docking

Drug Discovery, 2020, 14(33), 33-43

PDF