Synthesis and structure–activity relationships study of dithiolethiones as inducers of glutathione in the SH-SY5Y neuroblastoma cell line |
| |
| Institution: | 1. Department of Pharmaceutical Sciences, Manchester University College of Pharmacy, 10627 Diebold Rd, Fort Wayne, IN 46845, United States;2. Department of Microbiology and Immunology, Indiana University School of Medicine, 2101 Coliseum Blvd, Fort Wayne, IN 46805, United States;3. Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada;4. University of Ottawa Heart Institute, Ottawa, Ontario K1Y 4W7, Canada;5. Kidney Research Centre, Ottawa Hospital Research Institute, Ottawa Hospital, Ottawa, Ontario K1H 8L6, Canada;6. Center of Redox Biology and School of Veterinary Medicine and Biomedical Sciences, University of Nebraska at Lincoln, Lincoln, Nebraska 68583-0903;1. Department of Stem Cell Biology and Regenerative Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan;2. Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan;3. Department of Division of Anatomy and Cell Biology, Shiga University of Medical Science, Otsu, Shiga, Japan;4. Department of Critical and Intensive Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan;5. Division of Diabetes, Endocrinology and Metabolism, Departments of Medicine, Molecular and Cellular Biology, and Biochemistry, Baylor College of Medicine, Houston, Texas, United States;1. College of Pharmacy, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 305-764, Republic of Korea;2. College of Pharmacy, Hanyang University, Ansan, Gyeonggido 426-791, Republic of Korea;3. Bio-Evaluation Center, KRIBB, Ochang, Chungbuk, Republic of Korea;1. Department of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan;2. Division of Molecular Brain Science, Research Institute of Traditional Asian Medicine, Kinki University, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan;3. Department of Medicinal Pharmacognosy, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji 192-0392, Japan;4. Department of Anti-Dementia Functional Food Development, Research Center of Supercritical Fluid Technology, Graduate School of Engineering, Tohoku University, 6-6-7 Aoba, Aramaki, Aoba-ku, Sendai 980-8579, Japan;5. Laboratory of Kampo Medicines, Yokohama College of Pharmacy, 601 Matano-cho, Totsuka-ku, Yokohama 245-0066, Japan |
| |
| Abstract: | Parkinson’s disease is a neurodegenerative disorder that involves the degeneration of nigrostriatal dopaminergic neurons. Elevated levels of reactive oxygen species have been shown to deplete cellular levels of the ubiquitous antioxidant glutathione, leading to oxidative stress and eventual neuronal cell death. Dithiolethiones, a class of sulfur-containing heterocyclic molecules, have been shown to induce cellular production of glutathione in a variety of tissues, but have not been extensively evaluated in neurons. Herein, we report the synthesis and preliminary structure–activity relationships study of several substituted dithiolethiones. Three molecules were identified (D3T, CPDT, and 2d) that potently induced cellular glutathione in the SH-SY5Y neuroblastoma cell line. Furthermore, these compounds were found to provide neuroprotection in the 6-hydroxydopamine model of neurotoxicity. This study suggests that dithiolethione-mediated neuroprotection may have potential as a disease-modifying antiparkinsonian therapy. |
| |
| Keywords: | Dithiolethione Neuroprotection Glutathione |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
