Design and synthesis a mitochondria-targeted dihydronicotinamide as radioprotector.

Radiation-induced damage to the mitochondrial macromolecules and electron transfer chain (ETC), causing the generation of primary and secondary reactive oxygen (ROS) species. The continuous ROS production after radiation will trigger cell oxidative stress and ROS-mediated nucleus apoptosis and autophagy signaling pathways. Scavenging radiation-induced ROS effectively can help mitochondria to maintain their physiological function and relief cells from oxidative stress. Nicotinamide is a critical endogenous antioxidant helping to neutralize ROS in vivo. In this study, we designed and synthetized a novel mitochondrial-targeted dihydronicotinamide (Mito-N) with the help of mitochondrial membrane potential to enter the mitochondria and scavenge ROS. According to experiment results, Mito-N significantly increased cell viability by 30.75% by neutralizing the accumulated ROS and resisting DNA strands breaks after irradiation. Furthermore, the mice survival rate also improved with the treatment of Mito-N, by effectively ameliorating the hematopoietic system infliction under lethal dose irradiation.