組織内寄生虫症に有効な天然薬物のin vivoスクリーニング

金沢大学薬学部研究課題/領域番号:01771910, 研究期間(年度):1989出典：研究課題「組織内寄生虫症に有効な天然薬物のin vivoスクリーニング」課題番号01771910（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-01771910/）を加工して作

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

金沢大学自然科学研究科ピペラミド類{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\u27-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.研究課題/領域番号:06672096, 研究期間(年度):1994 – 1995出典：研究課題「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」課題番号06672096（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-06672096/066720961995kenkyu_seika_hokoku_gaiyo/）を加工して作

殺線虫活性を有する長鎖アミド類の研究

金沢大学薬学部研究課題/領域番号:63771885, 研究期間(年度):1988出典：研究課題「殺線虫活性を有する長鎖アミド類の研究」課題番号63771885（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-63771885/）を加工して作

幼線虫移行症に有効な天然薬物の検索

金沢大学薬学部研究課題/領域番号60771851, 研究期間(年度):1985出典：研究課題「幼線虫移行症に有効な天然薬物の検索」課題番号60771851（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-60771851/）を加工して作

幼線虫移行症に有効な天然薬物の検索

金沢大学薬学部研究課題/領域番号:61771807, 研究期間(年度):1986出典：研究課題「幼線虫移行症に有効な天然薬物の検索」課題番号61771807（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-61771807/）を加工して作

Genetic and Phenotypic Analyses of a Papaver somniferum T-DNA Insertional Mutant with Altered Alkaloid Composition

The in vitro shoot culture of a T-DNA insertional mutant of Papaver somniferum L. established by the infection of Agrobacterium rhizogenes MAFF03-01724 accumulated thebaine instead of morphine as a major opium alkaloid. To develop a non-narcotic opium poppy and to gain insight into its genetic background, we have transplanted this mutant to soil, and analyzed its alkaloid content along with the manner of inheritance of T-DNA insertion loci among its selfed progenies. In the transplanted T0 primary mutant, the opium (latex) was found to be rich in thebaine (16.3% of dried opium) by HPLC analysis. The analyses on T-DNA insertion loci by inverse PCR, adaptor-ligation PCR, and quantitative real-time PCR revealed that as many as 18 copies of T-DNAs were integrated into a poppy genome in a highly complicated manner. The number of copies of T-DNAs was decreased to seven in the selected T3 progenies, in which the average thebaine content was 2.4-fold that of the wild type plant. This may indicate that the high thebaine phenotype was increasingly stabilized as the number of T-DNA copies was decreased. In addition, by reverse transcription PCR analysis on selected morphine biosynthetic genes, the expression of codeine 6-O-demethylase was clearly shown to be diminished in the T0 in vitro shoot culture, which can be considered as one of the key factors of altered alkaloid composition

Synthesis, Antigenicity Against Human Sera and Structure-Activity Relationships of Carbohydrate Moieties from <em>Toxocara</em> larvae and Their Analogues

Stereocontrolled syntheses of biotin-labeled oligosaccharide portions containing the Galβ1-3GalNAc core of the TES-glycoprotein antigen obtained from larvae of the parasite <em>Toxocara</em> and their analogues have been accomplished. Trisaccharides Fuc2Meα1-2Gal4Meβ1-3GalNAcα1-OR (<strong>A</strong>), Fucα1-2Gal4Meβ1-3GalNAcα1-OR (<strong>B</strong>), Fuc2Meα1-2Galβ1-3GalNAcα1-OR (<strong>C</strong>), Fucα1-2Galβ1-3GalNAcα1-OR (<strong>D</strong>) and a disaccharide Fuc2Meα1-2Gal4Meβ1-OR (<strong>E</strong>) (R = biotinylated probe) were synthesized by block synthesis using 5-(methoxycarbonyl)pentyl-2,3,4,6-tetra-<em>O</em>-acetyl-β-D-galactopyranosyl-(1®3)-2-azide-4-<em>O</em>-benzyl-2-deoxy-α-D-galactopyranoside as a common glycosyl acceptor. We examined the antigenicity of these five oligosaccharides by enzyme linked immunosorbent assay (ELISA). Our results demonstrate that the <em>O</em>-methyl groups in these oligosaccharides are important for their antigenicity and the biotinylated oligosaccharides <strong>A</strong>, <strong>B</strong>, <strong>C</strong> and <strong>E</strong> have high serodiagnostic potential to detect infections caused by <em>Toxocara</em> larvae

Synthesis, Inhibitory Effects on Nitric Oxide and Structure-Activity Relationships of a Glycosphingolipid from the Marine Sponge Aplysinella rhax and Its Analogues

The novel glycosphingolipid, b-D-GalNAcp(1®4)[a-D-Fucp(1®3)]-b-D-GlcNAcp(1®)Cer (A), isolated from the marine sponge Aplysinella rhax has a unique structure, with D-fucose and N-acetyl-D-galactosamine moieties attached to a reducing-end N-acetyl-D-glucosamine through an a1®3 and b1®4 linkage, respectively. We synthesized glycolipid 1 and some non-natural di- and trisaccharide analogues 2-6 containing a D-fucose residue. Among these compounds, the natural type showed the most potent nitric oxide (NO) production inhibitory activity against LPS-induced J774.1 cells. Our results indicate that both the presence of a D-Fuca1-3GlcNAc-linkage and the ceramide aglycon portion are crucial for optimal NO inhibition