Interaction Of Phenylarsine Oxide(PAO) Derivatives With Thioredoxin Reductase, And Synthesis And Antioxidative Activity Of Analogues Of Lamellarine

Thioredoxin reductase (TrxR) is a FAD-containing selenoprotein belonging to the pyridine nucleotide-disulfide oxidoreductase family. TrxR, together with thioredoxin and NADPH, forms the thioredoxin system, which is crucial for a wide range of cellular functions, including redox regulation, oxidative stress defense, and DNA synthesis. Due to its critical role in various cancers, the thioredoxin system has attracted increasing interests in recent years.This thesis will focus on the development of small molecules and investigate the possible interactions of these molecules with TrxR, including the following 3 parts:1. Development of methods to detect the redox ststes of the C-terminal redox center within TrxR based on the interaction of phenylarsine oxide(PAO) with TrxR;2. Design and synthesis of small molecule inhibitors of TrxR using PAO as a leading molecule;3. Synthesis of Lamellarine R and it’s analogues, and study of their antioxidant activity in vitro.