Computational investigation of natural products against P2XR, P2X7 and cullin neddylation NEDD8 processing as potential multi-target Inhibitors.

Abstract

Alzheimer's disease and Esophageal cancer are among the most common diseases in the world. Treating these two diseases by targeting two specific proteins using molecules from different plants will be a promising potential process. The object of this study is to inhibit the P2X7 receptor and NEDD8 protein which are responsible for these two diseases respectively. After screening of more than 20 plants original from chlef State, Algeria. We selected the Salvia officinalis, Trigonella foenum-graecum and Phoenix dactylifera L seeds. The ethanolic extracts of Sage have the best inhibitory activity against Staphylococcu saurous ATCC6538 (Gram positive) with D=19mm. All the plants have antioxidant activity: IC50(sage)=0.191mg/ml , IC50(Fenugreek)=0.143mg/ml, IC50(dateseed)=0.193mg/ml .GC-MS analysis indicated several components in extracts. The study conducted a pharmacoinformatics analysis ―in silico‖ of 6 compounds from 75 bioactive compounds. In silico studies reveal that the inhibitor ligand Tricin interacts with NAE1, forming 9 amino acid bonds with ∆G = -7.8 kcal/mol and 7,4‘- Dihydroxyflavone interacts with P2X7 forming 7 amino acid bonds with ∆G = -6.8 kcal/mol . We finished our work with a new formulation which is Emulsuspension.