Thioredoxiin reductase (TrxR), which is overex pressed in many aggressive cancers, plays a crucial role in redox balance and antioxidant function, including defense of oxidative stress, control of cell proliferation, and regulation of cell apoptosis. Deactivation of TrxR can destroy the homeostatis of the cancer cells, inducing elevation of reactive oxygen species (ROS) levels and the oxidation of enzymatic substrates Here we synthesized and identified a new gold(I) small molecule (D9) that processes two strong electron-donating moieties i.e., 4-methylphenyl alkynyl and thionyldiphenyl phosephine exhibiting an enhanced p-pi conjuction effect. The resulting compound shows the increased soft Lewis-acids and the stability of gold(I) And we demonstrated that D9 could efficiently and specifically inhibit the activity of TrxR in vitro and in vivo, and it could effectively avoid the ligand exchange with albumin that was one of the mose abundant proteins in blood. We believe that these comprehensive studies on the relationship between the structure and performance will provide inspiring information on the precise synthesis and design of new compounds for targeting TrxR.
Zhang, D,Xu ZH,Xu, ZH,et al. Synthesis and Molecular Recognition Studies on Small-Molecule Inhibitors for Thioredoxin Reductase[J]. JOURNAL OF MEDICINAL CHEMISTRY,2014,57(19):8132-8139.
Zhang, D.,徐钟河.,Xu, ZH.,Yuan, J.,Zhao, YX.,...&Wang, H；李敬源.(2014).Synthesis and Molecular Recognition Studies on Small-Molecule Inhibitors for Thioredoxin Reductase.JOURNAL OF MEDICINAL CHEMISTRY,57(19),8132-8139.
Zhang, D,et al."Synthesis and Molecular Recognition Studies on Small-Molecule Inhibitors for Thioredoxin Reductase".JOURNAL OF MEDICINAL CHEMISTRY 57.19(2014):8132-8139.