Photoresponsive prodrug for regulated inhibition of indoleamine 2,3-dioxygenase 1 enzyme activity

Abstract

Targeting indoleamine 2,3-dioxygenase 1 (IDO1) has emerged as a promising therapeutic strategy for both cancer and Alzheimer's disease due to its critical role in modulating immune response and neurodegenerative processes. This study provides comprehensive evidence that thiourea derivatives of 2-imidazole-substituted 1-methyltryptamines exhibit strong binding affinity for the active site of IDO1. This interaction significantly inhibits the activity of the enzyme, which is an essential factor in tumour immune evasion and neuroinflammation. Furthermore, we have successfully developed a novel prodrug formulation that can restore the action of this potent IDO1 inhibitor upon photoirradiation. This prodrug represents a strategic advancement, allowing for spatial and temporal control of the therapeutic effect, potentially minimizing side effects and enhancing efficacy. Our findings underscore the potential of these compounds as valuable tools in the fight against cancer and Alzheimer's disease, paving the way for future research and clinical applications.