A computational method to predict the synergetic effect of Gallic acid and Curcumin analogues in controlling Pederin induced Contact dermatitis

Jannet Vennila

Abstract


Contact dermatitis is a skin infection caused by an insect Paederus fuscipes commonly known as the Rove beetle or Blister beetle. An endosymbiont bacteria residing inside this insect produces a toxin known as Pederin, is mainly responsible for the infection. Present study focuses on using analogues of Curcumin and Gallic acid, the natural phytochemicals from plants to control the Contact dermatitis. The structure of key enzyme Pederin Polyketide Synthase involved in the biosynthesis of this toxin was retrieved from Protein Data Bank. The structures of analogues of Curcumin and Gallic acid were mined through literature survey and they were used as ligands to dock and inhibit the activity of this enzyme. Molecular docking was carried out using Schrodinger GLIDE.  The ADME properties and pharmacophore models of the best docked phytochemicals was studied. Based on the docking score, pharmacophore model and ADME properties it was concluded that Curcumin and Gallic acid analogues can be used to inhibit the key enzyme Pederin Polyketide Synthase. Curcumin can synergistically enhance the  antioxidant effect of Gallic acid in controlling Contact dermatitis by  three way mechanism -  inhibition of synthesis of inflammatory cytokines by Curcumin, inhibition of NADH oxidase and the free radical formation by Gallic acid followed by inhibition of Pederin Polyketide Synthase by Curcumin and Gallic acid analogues. The future aspects of this research work can be done to understand and study the stability of Curcumin-Gallic acid binding by molecular simulation followed by  in vitro and in vivo assays.


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