title: Curcuminoids as inhibitors of thioredoxin reductase: a receptor based pharmacophore study with distance mapping of the active site.
abstract: Curcumin is the yellow pigment of turmeric that interacts irreversibly forming an adduct with thioredoxin reductase (TrxR), an enzyme responsible for redox control of cell and defence against oxidative stress. Docking at both the active sites of TrxR was performed to compare the potency of three naturally occurring curcuminoids, namely curcumin, demethoxy curcumin and bis-demethoxy curcumin. Results show that active sites of TrxR occur at the junction of E and F chains. Volume and area of both cavities is predicted. It has been concluded by distance mapping of the most active conformations that Se atom of catalytic residue SeCYS498, is at a distance of 3.56 from C13 of demethoxy curcumin at the E chain active site, whereas C13 carbon atom forms adduct with Se atom of SeCys 498. We report that at least one methoxy group in curcuminoids is necessary for interation with catalytic residues of thioredoxin. Pharmacophore of both active sites of the TrxR receptor for curcumin and demethoxy curcumin molecules has been drawn and proposed for design and synthesis of most probable potent antiproliferative synthetic drugs.
authors.affiliation: Deptartment of Bioinformatics, Indian Institute of information Technology, Deoghat Jhalwa, Allahabad 211012, India.
authors.forename: Durg Vijay
authors.initials: DV
authors.lastname: Singh
authors.forename: Krishna
authors.initials: K
authors.lastname: Misra
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