Thioredoxin Reductase and Organometallic Complexes: A Pivotal System to Tackle Multidrug Resistant Tumors?

Area of Science:

• Medicinal Chemistry
• Oncology
• Biochemistry

Background:

• Multidrug-resistant (MDR) cancers present a significant clinical challenge with poor prognoses.
• Resistance mechanisms involve tumor cells and their microenvironment, necessitating multi-targeting therapeutic strategies.

Purpose of the Study:

• To review the role of thioredoxin reductase (TrxR) inhibition as a therapeutic strategy for MDR tumors.
• To examine inorganic and organometallic gold complexes, as well as metallocifens, as TrxR inhibitors.

Main Methods:

• Literature review of studies on TrxR inhibitors.
• Analysis of molecular mechanisms of TrxR inhibition by various metal complexes.
• Discussion of the relationship between TrxR inhibition and cytotoxicity.

Main Results:

• Auranofin is a potent inorganic gold complex inhibitor of TrxR.
• Organometallic complexes, including gold(I), gold(III), and metallocifens (Fe, Os), also exhibit TrxR inhibitory activity.
• Similarities and differences in TrxR inhibition mechanisms among these complexes were identified.

Conclusions:

• TrxR inhibition is a promising strategy for targeting MDR tumors.
• Various gold complexes and metallocifens show potential as TrxR inhibitors.
• Further investigation into the relationship between TrxR inhibition and cytotoxicity is warranted.