Synthesis, activity exploration, molecular docking, and affinity assessment of theophylline derivatives as inhibitors targeting IDO1

Abstract

Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunomodulatory enzyme associated with tumor immune evasion, making it a promising target for cancer therapy. This study aimed to identify novel holo-IDO1 inhibitors with distinct structural scaffolds. A series of theophylline derivatives containing 1,2,3-triazole groups were designed and synthesized through the condensation of theophylline acetic acid and 4-aminophenylacetylene. Among the synthesized compounds, 3c and 3e exhibited the most potent inhibitory effects in IDO1 enzymatic activity assays. Molecular docking and affinity prediction analyses provided insights into the binding affinities and mechanisms of action of the lead compounds. Our findings suggest that theophylline derivatives are promising holo-IDO1 inhibitors, warranting further development for potential therapeutic applications.

Keywords

• theophylline
• 1,2,3-triazole
• ido1 enzymatic activity
• molecular docking
• affinity prediction