The Molecular Mechanism Study Of TrxR Activity Inhibition By Auranofin

Malignant tumor(cancer)is a serious disease that has a threat to human health.Early detection and prompt treatment is crucial to cure tumor.Currently,traditional diagnosis method is of low sensitivity and poor specificity.So developing antitumor drugs with better targeting property,safety and effectivity is a hot problem in the biomedical research,which plays an extremely important role in the therapy of tumor.In the field of biomedical,drug based on gold complex molecules are widely used in the diagnosis and treatment of tumor.As a Se-containing enzyme,thioredoxin reductase 1(TrxR1)involved in the process of tumor invasion and metastasis,and it plays an important role in the growth of tumor.Studies show that gold complex molecules can inhibit the activities of TrxR1 by forming gold-selenium bonds.Auranofin(AF)is a traditional medicine to treat arthritis,and has been widely used clinically,due to its better security and pharmacokinetic.Experimental studies found that AF can inhibit TrxR1's activity,and further inducing apoptosis of tumor cells.However,the intrinsic molecular mechanism is unclear.Our study carried out the molecular simulation research of AF-TrxR1,and explored the molecular mechanism between them.Then we made a comparison to TrxR1's natural ligand thioredoxin(thioredoxin,Trx).We found that AF binds to the active site of TrxR1 relying on the electrostatic interaction,van der Waals.The combination of AF-TrxR1 has a dynamic stability,and the effect is no less than the natural ligand Trx.Our studies on the characterization of biological properties of AF provides a new sight into the further development in tumor therapy.