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Int. J. Mol. Sci. 2017, 18(11), 2233; https://doi.org/10.3390/ijms18112233

Synthesis and Radioprotective Activity of Mitochondria Targeted Dihydropyridines In Vitro

1
Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China
2
Department of Physics, School of Sciences and Tianjin Collaborative Innovation Center of Chemical Science and Engineering, Tianjin University, Tianjin 300350, China
3
Department of Statistics, Tianjin University of Finance and Economics, Tianjin 300222, China
*
Author to whom correspondence should be addressed.
Received: 19 September 2017 / Revised: 22 October 2017 / Accepted: 23 October 2017 / Published: 25 October 2017
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

The radiation-induced damage to mitochondrial oxidative respiratory chain could lead to generating of superoxide anions (O2−) and secondary reactive oxygen species (ROS), which are the major resources of continuous ROS production after radiation. Scavenging radiation-induced ROS effectively can help mitochondria to maintain their physiological function and relief cells from oxidative stress. Dihydropyridines (DHPs) are biomimetic hydrogen sources that could protect cells against radiation damage. In this study, we designed and synthetized three novel mitochondrial-targeted dihydropyridines (Mito-DHPs) that utilize the mitochondrial membrane potential to enter the organelle and scavenge ROS. MitoTracker confirmed Mito-DHPs accumulation in mitochondria, and the DCFH-DA assay demonstrated effective ROS scavenging activity. In addition, the γ-H2AX and comet assay demonstrated the ability of Mito-DHPs to protect against both radiation and ROS-induced DNA strand breaks. Furthermore, Mito-DHP1 proved to be non-toxic and displayed significant radioprotection activity (p < 0.05) in vitro. Mito-DHPs are therefore promising antioxidants that could penetrate the membrane of mitochondria, scavenge excessive ROS, and protect cells against radiation-induced oxidative damage. View Full-Text
Keywords: reactive oxygen species (ROS); oxidative stress; mitochondrial targeted; radiation damage reactive oxygen species (ROS); oxidative stress; mitochondrial targeted; radiation damage
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Zhang, Y.; Wang, J.; Li, Y.; Wang, F.; Yang, F.; Xu, W. Synthesis and Radioprotective Activity of Mitochondria Targeted Dihydropyridines In Vitro. Int. J. Mol. Sci. 2017, 18, 2233.

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