1999 Fiscal Year Final Research Report Summary
Molecular Design of Hypervalent Iodine and Development of Drugs
| Project/Area Number |
09557181
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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 | 展開研究 |
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| Research Field |
Chemical pharmacy
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| Research Institution | Tokushima University |
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Principal Investigator |
OCHIAI Masahito Tokushima University, Pharmaceutical Sciences, Professor, 薬学部, 教授 (50127065)
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| Co-Investigator(Kenkyū-buntansha) |
OONO Sachio Maruko Pharmaceutical Co Ltd, Research Center, Director, 創薬研究所, 所長
SHIBUYA Masayuki Tokushima University, Pharmaceutical Sciences, Professor, 薬学部, 教授 (40027066)
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| Project Period (FY) |
1997 – 1999
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| Keywords | hypervalent compound / organoiodine / antifungal activity / alkynyliodane / alkenyliodane / DNA-cleaving activity / enediyne / radical |
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| Research Abstract |
A variety of alkenyl- and alkynyl(phenyl)iodanes were prepared from organosilanes via silicon-iodane exchange reations. The in vitro and in vivo antifungal activity of these organoidanes were studied and compared with that of amphotericin B and ketoconazole. (E)-1-Decenyliodane showed the weak in vitro antifungal activity. N-Octynyliodane showed a broad in vitro antifungal activity at low drug concentrations, inhibiting growth of Candida albicans. These alkenyl- and alkynyliodanes showed no in vivo antifungal activity.
DNA-cleaving activity of alkynyl(phenyl)iodanes was investigated by monitoring the conversion of closed circular (form I) to open circular (form II) and linear (form III) DNA. Ethynyl(phenyl)iodane and propynyl(phenyl)iodane showed moderate cleavage efficiency.
As a chemical model for a class of potent antitumor antibiotics, neocarzinostatin, the Myers-Saito type cyclizations of enediyne derivatives via γ- oxo ketene acetal intermediates generated by the neighboring group participation of naphtoate ester groups in acidic media were developed. Decarboxylative cycloaromatization of enediyne model compounds was also investigated.
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