2006 Fiscal Year Final Research Report Summary
Development of Glycoconjugated Hybrid Metal Complexes toward Frontier Medicinal Treatment and Elucidation of their Biomechanism
| Project/Area Number |
16350032
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Inorganic chemistry
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| Research Institution | Nara Women's University |
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Principal Investigator |
YANO Shigenobu Nara Women's University, Graduate School of Humanities and Sciences, Professor, 大学院人間文化研究科, 教授 (60011186)
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| Co-Investigator(Kenkyū-buntansha) |
OBATA Makoto Nara Women's University, Graduate School of Humanities and Sciences, Research Associates, 大学院人間文化研究科, 助手 (70343267)
MORIMOTO Keiko Nara Women's University Faculty of Human Life and Environment, Faculty of Human Life and Environment, Professor, 生活環境学部, 教授 (30220081)
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| Project Period (FY) |
2004 – 2006
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| Keywords | medicine / antifungal activity / growth inhibition / antitumor activity / sugar / thioglycoside / PDT / photosensitizer |
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| Research Abstract |
Medicinal inorganic chemistry is a discipline of growing significance in both therapeutic and diagnostic medicine. The rapidly expanding field of glycobiology has had a positive impact on medicinal inorganic chemistry. Introduction a carbohydrate to a metal-binding ligand has the ability to reduce toxicity, and improve solubility and molecular targeting to a wide variety of metal-based drugs. Six palladium (II) complexes as cisplatin derivatives with a sugar unit have been prepared. The complexes have been tested for in vivo cytotoxicity against P388 cells implanted in mice. All of Pd compounds are apparently nontoxic. A T/C value of 120% was obtained for maltose derivative at the dose of 400 mg/kg, which indicates that the compound may be endowed with antitumor activity. Radiolabelled carbohydrates have found widespread utility in the field of nuclear medicine. Our work in this area has centered on the development of carbohydrate-appended ^<99m>Tc complexes utilizing the {^<99m>Tc(CO)
… More
_3}+ core. A glucosamine-coupled derivative with a 2,2-dipicolylamine binding unit has shown exceptional in vitro stability and imaging studies are on-going. Due to the overall positive charge on this molecule, neutral forms are being prepared in order to test the effects of charge on the localization of these carbohydrate-based imaging agents. Photodynamic therapy (PDT) is an effective and selective treatment for cancer. Eight tetrakis [3-or 4-(β-D-glycopyranosyloxy) phenyl] chlorins were synthesized by means of the Whitlock method with diimide reduction and purified by reversed-phase thin layer chromatography. The cellular uptake of the eight chlorins was evaluated in HeLa cells. All glycoconjugated chlorins showed higher cellular uptake than tetraphenylporphyrin tetrasulfonic acid (TPPS). The photocytotoxicity of these compounds towards HeLa cells was examined. These photosensitizers had no cytotoxicity in the dark. The results indicate that the photocytotoxicity is not related simply to cellular uptake. Silver (I) complexes received attention because of their often displayed antimicrobial activity. The reaction of tris (2-bromoethyl) amine hydrobromide with sugar thiols or thioacetates leads to the formation of novel carbohydrate substituted tripodal NS_3 ligands. Complexation with silver (I) ions gives stable complexes. The highly water soluble complexes formed from the unprotected ligands show a wide spectrum of effective antimicrobial activities and their use lowers the cytotoxic and antiproliferative activities compared to the free silver salts. The field of medicinal inorganic chemistry has benefited greatly from advances in ligand design, leading to the development of improved diagnostic and therapeutic agents. Opportunities for the design of new metal-based and metal-binding agents will arise. Less
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[Journal Article] Cellular Uptake and Photocytotoxicity of Glycoconjugated Chlorins in HeLa Cells2005
Author(s)
S.Hirohara, M.Obata, S.Ogata, C.Ohtsuki, S.Higashida, S.Ogura, I.Okura, M.Takenaka, H.Ono, YSugai, Y.Mikata, M.Tanihara, S.Yano
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Journal Title
J. Photochem. Photobiol. B, Biology 78
Pages: 7-15
Description
「研究成果報告書概要(欧文)」より
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