| Project/Area Number |
62570458
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Dermatology
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| Research Institution | Nagoya City University |
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Principal Investigator |
MIZUNO Nobuyuki Professor, Nagoya City University Medical School, 医学部, 教授 (10079973)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAI Shinichi Assistant,, 薬学部, 助手 (40080212)
SAKAKIBARA Jinsaku Professor, Faculty of Pharmaceutical Sciences, 薬学部, 教授 (70080182)
ESAKI Kenji Assistant, Nagoya City University Medical School, 医学部, 助手 (90137109)
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| Project Period (FY) |
1987 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1988: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1987: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Chemical structure of oxidized 8-methoxypsoralen / Inhibition of anaphylatoxin C5a activity / Chemotactic activity of neutrophiles / 免疫複合体病の治療 / 8ーメトキシソラレン酸化物の化学構造 / 8ーメトキシソラレン / アナフィラトキシンC5a / 好中球遊走能抑制 / ソラレン酸化物 / アテフィラトキシン / 白血球遊走能制御 |
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| Research Abstract |
Treatment of anaphylatoxin C5a with 8-methoxypsoralen (8MOP) plus UVA inhibits the chemotaxis of polymorphonuclear neutrophiles (PMN) towards C5a. The mechanism of this reaction is considered as follows: 8MOP ^18MOP ^38MOP (1) ^38MOP+^3O_2 8MOP+^1O_2 oxidized product of 8MOP(8MOP-O_2) (2) 8MOP-O_2+C5a C5a 8MOP-O_2 conjugation ? (3) inactivation of C5a
Biological activity of 8MOP-O_2 persists for 2 weeks at room temperature. We determined the chemical structure of this bioactive 8MOP-O_2. It could be applied for the treatment of immune complex diseases as well as neutrophile-amplified dermatoses.
Several fractions of 8MOP-O_2 made with H_2O_2-NaOCl were separated by TLC and HPLC. Number of PMN migrated towards the mixture of C5a des Arg and each fraction was measured with blind well chamber. Bioactive fraction was obtained as a single compound. Its mass spectrum showed 264 (C_<13>H_<12>O_6, M^+). The structural elucidation was determined by infrared spectrum, ^1H NMR and ^<13>C NMR to be 2, 3-dihydro-2, 9, -dimethoxy-3-hydroxy-7-oxo-7H-furo [3, 2-g][1]benzopyran.
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