ピペラミドおよびマラバリコン類の殺線虫作用に於ける構造活性相関

Structure-Activity Relationship in Nematocidal Activity of Piperamides and Malabaricones

Research Project Number:06672096

Principal Investigator

  • FY1994~FY1995

    • 木内 文之
    • KIUCHI, Fumiyuki
    • Researcher Number:60161402
    • 金沢大学・自然科学研究科・助手


Co-Investigators

    • 近藤 力王至
    • KONDO, Kaoru
    • Researcher Number:00079724
    • 金沢大学・医学部・助教授
    • 津田 喜典
    • TSUDA, Yoshisuke
    • Researcher Number:40077508
    • 金沢大学・薬学部・教授

Basic Information of this Research Project(Latest Year)

  • Project Year

    FY1994~FY1995

  • Research Field

    化学系薬学

  • Screening Classification

  • Research Category

    一般研究(C)

  • Research Institution

    金沢大学

  • Budget Amount

    • Total:¥600000
    • FY1995:¥600000 (Direct:¥600000)

Abstract(Latest Report)

ピペラミド類{Ar (CH_2)_nCO-X : Ar=芳香環,X=アミン}については,芳香環部(Ar)としてphenyl,p-methoxyphenyl,m,p-dimethoxyphenyl,3,4methylenedioxyphenyl,p-hydroxyphenyl,m,p-dihydroxyphenylのいずれか,またアミン部(X)としては,pyrrolidine (C),またはN-methylpiperazine (M)を持ち,メチレン鎖の長さ(n)が6から14の同族体を合計76種合成し,各々の殺線虫活性を測定した.その結果,殺線虫活性は側鎖の長さとアミン部の種類にって大きく異なり,水酸基を持たない化合物では,log Pで代表される化合物の疎水性と親水性のバランスが一定の範囲内で最大活性を示すことがわかった.これに対し,フェノール性水酸基を持つ化合物は,前記化合物群よりlog Pが小さいところで最大活性を示しており,単なるアミド化合物とは異なる作用機序あるいは作用部位を持っていることが推察された.

一方マラバリコン類{Ar (CH_2)_nCOAr^1}については,種々の天然型マラバリコン(Ar^1=o,o^1-dihydroxyphenyl)およびAr=phenylのものについてAr^1をphenyl,o-,m-hydroxy-phenyl,o,m-dihydroxyphenyl,o,p-dihydroxyphenyl,o,m-dimethoxyphenyl,o,p-dimethoxyphenylに変えたものを合成し,その活性を調べた.その結果,Ar^1のo,o^1-位またはp-位に水酸基を持つものが強い活性を示し,中でもAr^1p-hydroxyphenylのものが,犬蛔虫に対する最小致死濃度(MLC)が8μMと,天然から得られているマラバリコンC(MLC=5μM)やマラバリコンA(MLC=8μM)に匹敵する殺線虫活性を示した.

Seventy six piperamides and their analogs with twenty malabaricones and their analogs were synthesized and their nematocidal activity against second-stage larvae of dog roundworm, Toxocara canis, were examined. Among the piperamide analogs, the activity was largely dependent on the length of the alkyl chain and the nature of the amine moiety. The alkyl chain length which showed the strongest activity in a series of homologues were m=9 for the pyrrolidine amides and m=11 for the N-methylpiperazine amides. Calculated log P values of the activity of these compounds.

Among the naturally occurring malabaricones which have two oxygen functions at both o-and o'-positions of the acetophenone moiety, malabaricone A showed the strongest activity. Among the synthetic malabaricone analogs without any substituent on the aryl moiety, at least one free hydroxy group was essential for the activity. A hydroxy group at the ortho position or at the benzylic position (introduced by reduction of the ketone or conjugation with the hydroxy group on the benzene ring) of the acetophenone moiety seemed to be important for the activity.

URI of this page

http://kaken.nii.ac.jp/d/p/06672096.en.html