| Project/Area Number |
01303012
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| Research Category |
Grant-in-Aid for Co-operative Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Physical pharmacy
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| Research Institution | Chiba University |
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Principal Investigator |
YAMANE Yasuhiro Chiba University, Faculty of Pharmaceutical Sciences, Emeritus Professor, 薬学部, 名誉教授 (40009155)
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| Co-Investigator(Kenkyū-buntansha) |
SAKURAI Tsutomu Kyoto Pharmaceutical University, Department of Analytical Chemistry, Professor, 教授 (30065916)
NOJI Masahide Nagoya City University, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (70080190)
SUGIURA Yukio Kyoto University, Institute for Chemical Research, Professor, 化学研究所, 教授 (40025698)
YOKOYAMA Akira Kyoto University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (90025685)
HANAKI Akira National Institute of Radiological Sciences, Chief, 薬理化学部, 室長
宮崎 元一 金沢大学, 薬学部, 教授 (50009164)
山内 脩 名古屋大学, 理学部, 教授 (70029643)
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| Project Period (FY) |
1989 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥8,800,000 (Direct Cost: ¥8,800,000)
Fiscal Year 1991: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1990: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1989: ¥4,700,000 (Direct Cost: ¥4,700,000)
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| Keywords | Antitumor metal complex / Platinum complexes / elsamicin A - iron complex / ^<62>Zn / ^<62>Cu Generator system / Dimethyldithiosemi-carbazone-Cu complex / Metal complex for enzyme model / oxidases model / P-450 model / ヒスチジンペプチド-グリシン錯体 / Pー450 / 毒性軽減 / 脳内SOD様薬剤 / ジチオセミカルバゾン銅錯体 / フェニルアラニンヒドロキシラ-ゼ / P-450 / 99m-テクネチウム錯体 / 脳血流核医学画像診断薬 |
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| Research Abstract |
Cis-Diammiedichloroplatinum (II) (CDDP) is now widely and successfully used clinically, especially in the therapy of testicular tumors, tumors of the bladder and ovarian cancer. 1, 2-Diaminocyclohexanedichloroplatinum (II) has a potent antitumor activity but is virtually insoluble in water. 1, 2-Diaminocyclohexane (ascorbato) platinum (II) which is water-soluble was synthesized and had potent antitumor activity, especially against Lewis lung carcinoma cells. The value of blood urea nitrogen was also measured as a marker of renal toxicity. The results with ascorbatoplatinum complexes showed lightening of renal toxicity. 1R, 2R-diaminocyclohexane[1, 3-bis- (diphenylphosphin) propane](NO_3)_2 as platinum complexes containing diphosphines and amities were found to have a great antitumor activity against in vivo leukemia L1210.
The preferential cutting sites of DNA strand scission with elsamicin A - iron complex are on the bases adjacent to the 3'-side of guanine residues such as 5'-GN sites
… More
, in particular 5'-GG sites. An acetylation of the amine group on the elsamicin A sugar portion was found to play an interesting switch function for the activity of elsamicin A.
^<62>Cu-labeling of human serum albumin-dithiosemicarbazone (HSA-DTS) conjugate was performed using a newly developed ^<62>Zn/^<62>Cu generator system. In vivo blood clearance of Cu-HSA-DTS was similar to ^<13l>I-HSA, indicating the high applicability of Cu-HSA-DTS as a method for plasma volume measurement. To achieve stable Cu-labeling, dithiosemicarbazone (DTS) containing bifunctional chelating agent was preincubated to the HSA molecule as a Cu binding site.
As an enzyme model of oxidases, Cu (II)-peptides such as glycylglycylglycine were shown to coordinate to glutathilone yielding transient ternary complexes. Copper (II) complexes with polyamine-N-polycarboxylate such as EDTA can yield OH radical by the reaction with H_2O_2 in the presence of biological reductants such as L-ascorbic acid and L-cysteine. A bis (thiolato) complex of iron-porphyrin exhibiting a "split Soret band" was prepared with Fe (III) protoporphyrin dimethyl ester, glutathione dimethyl ester and tetrabutylammonium hydroxide in acetone solvent. This structure of the complex was characterized by comparing their electronic absorption and electron spin resonance spectra with those of thiolate adducts of cyctochrome P-450 and their chemical model complexes. Less
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