Das Niku Moni, Prusty Biswa Mohan, Sahoo Adyasa, Mazumder Priyanka, Chauhan Suravi, Hazarika Gunanka, Kumar Sachin, Dhabal Debdas, Manna Debasis
Indian Institute of Technology Guwahati, Chemistry Guwahati Assam India
Indian Institute of Technology Guwahati, Center for the Environment Guwahati Assam India.
RSC Med Chem. 2025 May 9. doi: 10.1039/d5md00061k.
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.
由于吲哚胺2,3-双加氧酶1（IDO1）在调节免疫反应和神经退行性过程中起关键作用，靶向IDO1已成为一种有前景的癌症和阿尔茨海默病治疗策略。本研究提供了全面的证据，表明2-咪唑取代的1-甲基色胺的硫脲衍生物对IDO1的活性位点具有很强的结合亲和力。这种相互作用显著抑制了该酶的活性，而该酶是肿瘤免疫逃逸和神经炎症的一个重要因素。此外，我们成功开发了一种新型前药制剂，在光照射后可恢复这种强效IDO1抑制剂的作用。这种前药代表了一种战略进步，能够实现治疗效果的时空控制，有可能将副作用降至最低并提高疗效。我们的研究结果强调了这些化合物作为对抗癌症和阿尔茨海默病的有价值工具的潜力，为未来的研究和临床应用铺平了道路。
