Polyfunctionalized N-Arylsulfonyl Indoles: Identification of (E)-N-Hydroxy-3-{3-[(5-(3-(piperidin-1-yl)propoxy]-1H-indol-1-yl)sulfonyl]phenyl}acrylamide (MTP150) for the Epigenetic-Based Therapy of Parkinson's Disease

多功能化N-芳基磺酰基吲哚:(E)-N-羟基-3-{3-[(5-(3-(哌啶-1-基)丙氧基]-1H-吲哚-1-基)磺酰基]苯基}丙烯酰胺 (MTP150) 的鉴定及其在帕金森病表观遗传治疗中的应用

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Abstract

Herein, we have identified the polyfunctionalized 1-(phenylsulfonyl)-1H-indole-2-carboxylic acid derivative MTP150 for the treatment of neurodegenerative diseases owing to its efficacy in reducing protein aggregation, modulating matrix metalloproteinase activity, mitigating neuroinflammation, and enhancing DNA damage repair pathways across in vivo Caenorhabditis elegans models of Alzheimer's disease, Parkinson's disease (PD), and Huntington's disease. Further experiments in an in vivo Drosophila model of PD showed that MTP150 increased motor performance, reduced oxidative stress levels, and restored mitochondrial function in model flies. In addition, MTP150 exhibited neuroprotective effects in PD model cells, thereby supporting its therapeutic potential for this disease.

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