5-Deazaflavin (TND1128) and its hybrid analogs are cytoprotective against hydrogen peroxide (H ₂ O ₂ )-induced oxidative stress

Increased production of reactive oxygen species (ROS) and oxidative stress are implicated in mitochondrial dysfunction, contributing to the pathogenesis of many neurodegenerative diseases. Research is ongoing into a new treatment approach for neurodegeneration, focusing on reactivating dysfunctional mitochondria. Some 5-deazaflavins, such as 10-ethyl-3-methylpyrimido[4,5- b ]quinoline-2,4(3 H ,10 H )-dione (TND1128), and four analogs of 5-deazaflavin, including β-nicotinamide mononucleotide (β-NMN), demonstrate efficient self-redox abilities similar to β-NMN, making them potential activators of mitochondrial energy synthesis. This study examines whether TND1128 and its analogs have protective effects against cellular impairment induced by oxidative stress. These compounds exhibit proliferative potential against normal cells. Moreover, TND1128 and its analogs significantly improved cell viability against hydrogen peroxide (H ₂ O ₂ )-induced oxidative stress injury. Our study confirms the cytoprotective effect of these 5-deazaflavins through mitochondrial activation. We anticipate TND1128 and its analogs will serve as mitochondria-stimulating drugs capable of rescuing deteriorating neurons in aging or diseases.