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@@@]ú±@‰~@i‘åŠw‰@¶D1j


@Ž¾•a‚Ì”­Ç‚â—\Œã‚ÉŠÖ‚µ‚Ä‚¢‚é—lX‚È—vˆö‚́Au“à•”ŠÂ‹«i¶—“IAˆâ“`“Ij—vˆöv‚Ɓui’¼Úl‘Ì‚ðŽhŒƒ‚µANP‚µ‚ ‚é‚¢‚͉e‹¿‚·‚éj—vˆöv‚ƁA‚»‚Ì“ñŽÒ‚ðŽæ‚èˆÍ‚ށuŠO•”ŠÂ‹«iŽ©‘RŠÂ‹«AŽÐ‰ïŠÂ‹«j—vˆöv“™‚ÉŠT•Ê‚³‚ê‚éB‚±‚ê‚ç‚Ì—vˆö‚ªAŠÖ˜A‚µ‚ĉe‹¿‚µ‚ ‚Á‚ÄŽ¾•a‚Ì”­Ç‚ÉŽŠ‚Á‚Ä‚¢‚éB

@‹ß”NAŽ¾•a‚Ì—\–h‘΍ô‚É‚¨‚¢‚āA]—ˆ‚̐¬l•a‚ð‘ΏۂƂµ‚½u“ñŽŸ—\–hv‚æ‚èi“W‚µ‚āAu¶ŠˆKŠµ•av‚̍l‚¦•ûAŒ’N“I‚Ȑ¶ŠˆKŠµ‚ðŠm—§‚·‚邱‚ƂŁAŽ¾•a‚Ì”­Ç‚»‚Ì‚à‚Ì‚ð—\–h‚·‚éuˆêŽŸ—\–hv‚̍l‚¦•û‚ªdŽ‹‚³‚ê‚Ä‚¢‚éB‚±‚ÌŠÏ“_‚É‚¨‚¢‚āA‰q¶Šw‚Ƃ́A—lX‚È”­ÇiŒ’N‚Ì‘jŠQj‚ÌŒ´ˆö‚𖾂炩‚É‚µ‚āA‚»‚ÌŒ´ˆö‚Ì”rœAŒ´ˆö‚©‚ç‚Ì–hŒä‚ð‚·‚é‚±‚ƂŁAŒ»Ý‚ÌŒ’N‚ðˆÛŽ‚µA‚³‚ç‚É‚Í‘i‚·‚邱‚Æ‚ð–ÚŽw‚µ‚½—\–hˆãŠw‚ð‰ðà‚·‚邱‚Æ‚É‚ ‚è‚Ü‚·B

Œ¤‹†ƒe[ƒ} F@Dihydropyrazine—ނ̉Ȋw

@ƒOƒ‹ƒRƒTƒ~ƒ“‚©‚ç‚̕ω»¶¬•¨‚Å‚ ‚éƒWƒqƒhƒƒsƒ‰ƒWƒ“iDHPj—Þ‚ªADNA½Ø’fì—piYamaguchi, T., et. al. : Dihydropyrazine Derivatives as a New Type of DNA Strand Breaking Agent, Biol. Pharm. Bull ., 19 , 1261-1265, 1996)‚ðŽ¦‚·Ž–‚𖾂炩‚É‚µ‚ĈȗˆA ‚»‚̐ؒfì—p‚Ì‹@\‚̉𖾂ð–ÚŽw‚µ‚Ä‚¢‚éB DHP—Þ‚ªA¶‘Ì“à‚É‚¨‚¢‚Ä‚Í AGE ( Advanced Glycation Endproducts ) ‚̈êŽí‚Æ‚µ‚āAƒOƒ‹ƒR[ƒX‚æ‚萶¬‚³‚êA¶‘Ì‚Ö‰½‚ç‚©‚̉e‹¿‚ð—^‚¦‚Ä‚¢‚é‚Ɛ„’肳‚ê‚éB“œ‚Ƃ̈ö‰ÊŠÖŒW‚©‚çAu“œ”A•a‚¨‚æ‚Ñ‚»‚̍‡•¹Ç‚Ì”­Ç‚ÌŒ´ˆö‚ÉŠÖ‚í‚éŠî‘bŒ¤‹†v‚Æ‚µ‚āAŒ¤‹†’†‚Å‚ ‚éB‚±‚ê‚܂łɁAin vitro‚É‚¨‚¯‚é DHP—ނ̉»Šw•Ï‰»‚𖾂炩‚É‚µ‚Ä‚«‚½B¡Œã‚́A‚»‚̉ž—p–ʂ̐¬‰Ê‚𓾂邱‚Æ‚ð–Ú“I‚Æ‚µ‚āAin vivo ‚É‚¨‚¯‚é DHP—Þ‚Ì‹““®‚𒲂א¶‘Ì‚Æ‚ÌŠÖ‚í‚è‚Ì–Ê‚Å‚Ì“WŠJ‚ð–ÚŽw‚µ‚Ä‚¢‚éB

‚±‚ê‚܂łɁAˆÈ‰º‚ɏq‚ׂé‚悤‚ȁADHP—ނ̏”«Ž¿‚ª–¾‚ç‚©‚É‚È‚Á‚Ä‚«‚½B

@@@@@1. High chemical reactivity ( in vitro )
@@@@@2. DNA strand-breaking activity ( in vitro )
@@@@@3. Generation of hydroxyl and carbon-centered radicals( in vitro )
@@@@@4. Distribution into the brain and spinal cord in mouse ( in vivo )
@@@@@5. Induction of apoptosis in cultured cell ( in vitro )
@@@@@6. Activation of MAP kinase in cultured cell ( in vitro )
@@@@@7. Growth inhibition effect in E.coli and Lactobacillus casei ( in vivo )
@@@@@8. Induction of mutagenesis in E.coli ( in vivo )
@@@@@9. Lethal effect in E.coli and Lactobacillus casei ( in vivo )
@@@@ 10. Anti-virus effect( in vivo )
@@@@ 11. Inhibition of cardiac function in rat( in vivo )
@@@@ 12. Inhibition of GAPDH on glycolytic cycle( in vitro )
@@@@ 13. Inhibition of beating in ventricular clusters( in vitro )

@in vitro ‚Ì”½‰ž‚ŁAƒOƒ‹ƒR[ƒX‚ªƒAƒ~ƒmŠî‚ðŽæ‚荞‚݁AƒAƒ~ƒm“œ‚É‚È‚èA‚±‚ꂪ2•ªŽqŠÔ’E…k‡‚·‚邱‚ƂŁADHP—U“±‘̂𐶐¬‚·‚邱‚Æ‚Í–¾‚ç‚©‚Å‚ ‚éBŒÌ‚ɁAin vivo ‚É‚¨‚¢‚Ä‚àA”ñy‘f“I‚É“¯—l‚È”½‰ž‚ªis‚µ‚Ä‚¢‚邱‚Æ‚ª—\‘ª‚³‚ê‚éB‚µ‚½‚ª‚Á‚āA‚»‚Ì DHP—ނ̐¶‘̂ւ̉e‹¿‚𖾂炩‚É‚·‚邱‚ƂŁA DHP—Þ‚ÆŽ¾•a‚Ƃ̈ö‰ÊŠÖŒW‚ª–¾‚ç‚©‚ɂȂ邱‚Æ‚ªŠú‘Ò‚³‚ê‚éB DHP—Þ‚ª“œ—R—ˆ‚̕ω»¶¬•¨‚Å‚ ‚邱‚Æ‚©‚çA‚Ü‚¸‚Í“œ”A•a‚¨‚æ‚Ñ‚»‚̍‡•¹Ç‚Æ‚ÌŠÖ˜A‚ð—\‘ª‚µ‚āAŒ¤‹†‚ði‚ß‚Ä‚¢‚邪A’†•_Œo×–E‚ւ̏WÏiT. Yamaguchi et al., Biol.Pharm.Bull ., 26 ,1523-1527, 2003)FThe Behavior of Dihydropyrazine with DNA Strand-Breakage Activity in vivo jA‚»‚̏ê‚ł̃Aƒ|ƒg[ƒVƒX—U“±‚ª„’肳‚ê‚éB‚µ‚½‚ª‚Á‚āA_Œo×–E‚ÌŽ€‚É‹Nˆö‚·‚é“ï•a‚ÆDHP—Þ‚ÌŠÖ‚í‚è‚à—\‘ª‚³‚ê‚éó‹µ‚Å‚ ‚éB‚Ü‚½Amutagenesis ‚Ì—U“±iS.Takechi, et.al.,: Growth inhibition and mutagenesis induced in Escherichia coli by dihydropyrazines with DNA strand-cleaving activity: Mutat. Res., 560, 49-55, 2004) ‚à–¾‚ç‚©‚É‚È‚Á‚½B‚±‚ÌŽ–‚́A“œ”A•a‚ÆŠà‚Æ‚ÌŠÖ˜A‚ª•ñi Diabetes Frontier ,13 (5), 2002 : “ÁWF“œ”A•a‚ƈ««Žîá‡)‚³‚ê‚Ä‚¢‚邱‚Æ‚©‚ç‚àADHP—ނƐ¶‘Ì‚Æ‚Ì•‰‚ÌŠÖ‚í‚èiŽ¾•a‚Ƃ̈ö‰ÊŠÖŒWj‚ªA‚æ‚è‹­‚­—\‘ª‚³‚ê‚éB

@DHP—Þ‚ÌDNA½Ø’fì—p‚ðA‰‚ß‚Ä–¾‚ç‚©‚É‚µ‚½‚͉̂äX‚Å‚ ‚éB‚µ‚©‚àA‚±‚ÌDHP—Þ‚Í•sˆÀ’è‚ňµ‚¢“ï‚¢‰»‡•¨‚Å‚ ‚邪AŒ¾‚¢Š·‚¦‚ê‚΁A‰»Šw“I‚É”½‰ž«‚ª‚‚¢‰»‡•¨‚Å‚ ‚éB‚µ‚½‚ª‚Á‚āA¶‘Ì“à‚Å‚ÌDHP—Þ‚Ì‘¶Ý‚𒼐ړI‚É’²‚ׂé‚͍̂¢“ï‚Å‚ ‚èA‚Ü‚½A‚»‚Ì‘¼‚̏”«Ž¿‚ɂ‚¢‚Ä‚à‚Ù‚Æ‚ñ‚Ç’m‚ç‚ê‚Ä‚¢‚È‚¢B‚Æ‚±‚낪ADHP—Þ‚ÌŽ_‰»i’E…‘f”½‰žj‚É‚æ‚é•Ï‰»¶¬‘Ì‚Å‚ ‚éƒsƒ‰ƒWƒ“—ނ́AH•i‚̐¶ŽYA‰ÁHA’²—‚̉ߒö‚Ő¶¬‚³‚êAH•i’†‚Ì‘¶Ý‚͍–¡¬•ª‚Æ‚µ‚ÄŽü’m‚ÌŽ–ŽÀ( J.Agr.Food Chem ., 21 ,22-30,1973)‚Å‚ ‚éB‘¼•ûA¶‘Ì“à‚̃sƒ‰ƒWƒ“—Þ‚Ì‘¶Ý‚́A“œ”A•aŠ³ŽÒ‚ÌŒŒ’†A”A’†‚Ì‘‰Á‚ª‚·‚Å‚É•ñi Analytical Chemistry ,45 ,763-767,1973j‚³‚ê‚Ä‚¢‚éB‚±‚̃sƒ‰ƒWƒ“—Þ‚Ì‘O‹ì‘Ì‚Å‚ ‚éDHP—ނ̐¶‘Ì“à‚ł̐¶¬A‚»‚µ‚Ä‚»‚Ì‘¶Ý‚Æ•ª•z‚ªA¶‘Ì‚Ö‚¢‚©‚È‚é‰e‹¿‚ð‹y‚Ú‚·‚©‚𖾂炩‚É‚·‚邱‚Ƃ́Al‚ÌŒ’NˆÛŽ‚ÆŽ¾•a‚©‚ç‚Ì–hŒä‚ÉŽ‘‚·‚é‚à‚̂ƍl‚¦‚Ä‚¢‚éB

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