Project/Area Number |
14380409
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Biomedical engineering/Biological material science
|
Research Institution | Tokyo Metropolitan University |
Principal Investigator |
KAWAKAMI Hiroyoshi Tbkyo Metropolitan University, Dept. of Applied Chemistry, Associate Professor, 工学研究科, 助教授 (10221897)
|
Co-Investigator(Kenkyū-buntansha) |
NAGAOKA Shoji Tokyo Metropolitan University, Dept. of Applied Chemistry, Professor, 工学研究科, 教授 (30254147)
KUBOTA Sunao St. Marianna University, School of Medicine, Professor, 第一外科, 教授 (20075500)
|
Project Period (FY) |
2002 – 2004
|
Project Status |
Completed (Fiscal Year 2004)
|
Budget Amount *help |
¥10,300,000 (Direct Cost: ¥10,300,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2003: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2002: ¥5,300,000 (Direct Cost: ¥5,300,000)
|
Keywords | Metallonornhyrin / Artificial Enzyme / Nanocarrier / Ischemia / reperfusion / Anticancer Drug / Antioxydant Drug / 糖鎖 / 虚血再潅流 / SOD活性 / ミトコンドリア / In vivo評価 / 活性酸素 |
Research Abstract |
Reactive oxygen species (ROS^1) are considered to be implicated in the pathogenesis of a number of diseases, such as atherosclerosis, cancer, and Alzheimer's disease. Their toxic effects are amplified by pathological events including neutrophil activation, hyperoxia, metabolism of redox-active drugs, radiation exposure, and ischemia/reperfusion. Subsequently, the overproduced ROS,'such as superoxide radical anion (O_2^<.->), cause the membrane damage resulting from lipid peroxidation, as well as the attack on proteins and nucleic acids. Therefore, antioxidant enzymes are useful for the therapy of ROS-mediated injuries and diseases. We have synthesized a macromolecular Mn-porphyrin for enhancing half-life in the blood circulation. However, these Mn-porphyrins lack the ability to target the cells overproducing O_2^<.->, although the selective delivery of SOD mimics into every particular cell is promising for a radical approach to various therapy In this study, we have synthesized a new SOD mimic to eliminate in vivo free radicals. We have synthyesized novel metalloporphyrin derivatives as SOD mimics. In addition, we have demonstrated the anticancer effects of metalloporphyrin derivatives with SOD activity. Finally, I have synthesized novel drug carriers containing metalloporphyrin derivatives as SOD mimics.
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