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研究生:林君郁
研究生(外文):Lin, Chun-Yu
論文名稱:第一部份:黑星櫻成份之研究第二部份:黑星櫻成份,苯駢塞井酮類及類似物對黃嘌呤氧化脢之抑制作用
論文名稱(外文):Part I:Studies on the Constituents of Prunus phaeosticta (HANCE) MAXIM. Part II:Inhibition of Xanthine Oxidase by the Constituents of Prunus phaeosticta (HANCE) MAXIM. and Benthiazinone Analogues.
指導教授:許秀蘊許秀蘊引用關係
指導教授(外文):Sheu Shiow-Yunn
學位類別:碩士
校院名稱:台北醫學院
系所名稱:藥學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:1997
畢業學年度:85
語文別:中文
論文頁數:106
中文關鍵詞:蒲公英賽醇黃嘌呤氧化脢抑制劑塞侳類苯駢塞井酮類
外文關鍵詞:beta-香樹脂醇beta-穀甾醇-3-O-beta-D-葡萄糖甘beta-amyrintaraxerolbeta-sitosterol-3-O-beta-D-glucosidexanthine oxidase inhibitorthiazolesbenzothiazinones
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第一部份:黑星櫻成份之研究 臺灣所產之黑星櫻為較稀有之梅屬薔薇
科植物.據文獻記載,梅屬植物有潤肺化痰,潤燥,利水,固精,收歛及治療良
性前列腺增殖等效用.故本實驗分離純化黑星櫻之成份,與同屬已知成份做
一對照比較,以期能發現新的有效成份.經由各種管柱層析,由黑星櫻氯仿
層分離出七個化合物.利用光譜測定及化學方法分析,目前鑑定出三個化合
物為beta-香樹脂醇(1),蒲公英賽醇(2),beta-穀茲醇-3-O-beta-D-葡萄糖
甘(3). 第二部份:黑星櫻成份,本駢塞井酮類及類似物對黃嘌呤氧化脢之
抑制作用 根據文獻,黃嘌呤氧化脢與痛風,缺血後組織再灌流傷害,腦瘤,
急性胰臟炎及肝炎等疾病有關.故本實驗探討黑星櫻成份,塞侳類與本駢塞
井酮類化合物對黃嘌呤氧化氧化脢之抑制作用.如測試抑制百分比,抑制百
分之五十濃度(IC50),抑制型態及抑制常數(Ki),以其對治療或預防黃嘌呤
氧化脢相關疾病有所幫助.次黃嘌呤受黃嘌呤氧化脢的催化作用轉變成黃
嘌呤,然後此脢在催化黃嘌呤變尿酸,而尿酸在紫外線波長295nm處有最大
吸收.故利用紫外線光譜測定尿酸的吸光值變化速率,做為黃嘌呤氧化脢之
活性指標.抑制型態及抑制常數依據Line-weaver-Burk plot公式求得.結
果顯示,黑星櫻成份對黃嘌呤氧化脢抑制作用非常微弱.苯駢塞井酮類化合
物中,則以2-amino-4H-1,3-benzothiazin-4-one(IC50=5.54uM,Ki=5.12
uM)及2-guanidino-4H-1,3-benzothiazin-4-one(IC50=5.60uM,Ki=19.47
uM)較具活性,抑制型態分別屬於不競爭型與混合型(不競爭型-非競爭型)
抑制劑.而塞侳類化合物中只有rhodan-ine(IC50=121.40uM,Ki=206.23uM)
具微弱的抑制效果,抑制型態屬混合型(不競爭-非競爭型)抑制劑.
Part I. The Constituents of Prunus phaeosticta (HANCE) MAXIM.
Prunus phaeosticta (HANCE) MAXIM. is a novel Prunus plant of
Rosaceae in Taiwan. Prunus plants have been used as nourish the
lung, resalve sputum, for treatment of dryness-syndrome, also as
diuretic, tonic, astringent and for treatment of benign prostate
hyperplasia. In this study, the constituents of the plant were
isolated, and compared with the constituents of other Prunus
spp. By variaus column chromatography, seven compounds were
isolated from the chloroform soluble fraction. Three compounds,
beta-amyrin(1), taraxerol(2) and beta-sitosterol-3-O-beta-D-
glucoside(3) were characterized by spectroscopic data and
chemicalmethods, and four constituents remain to be analyzed.
Part II. Inhibition of Xanthine Oxidase by the Constituents of
Prunus phaeosticta (HANCE) MAXIM. and Benzothiazinone Analogues.
According to the literature, xanthine oxidaseis related to
several diseases such as gout, tissue reperusion iniuries, brain
tumors, acute pancreatitis and hepatitis. In this study, the
constituents of Prunus phaeosticta (HANCE) MAXIM., thiazoles and
benzothiazinones have been tested for their inhibitory, effects
on xanthine oxidase:determination of percent inhibition, IC50,
mode of inhibition and the apparent inhibition constant (Ki). It
is expected that xanthine oxidase inhibitors are useful for the
treatment or prevention of these diseases mentioned as above.
The enzyme, xanthine oxidase catalyses the oxidation of
hypoxanthine to xanthine and of xanthine to uric acid which has
wavelength of 295 nm. Uric acid was thus forming basis for a
spectrophotometric assay of the activity of xanthineoxidase.
According to the Lineweaver-Burk plot equation, mode of
inhibition andthe apparent inhibition constants (Ki) were
estimated. The results showed that the constituents of Prunus
phaeosticta (HANCE) MAXIM. showed very weak inhibitory effect on
xanthine oxidase. On the other hand, benzothiazinone analogues,
2-amino-4H-1,3-benzothiazin-4-one (IC50-5.54uM, Ki=5.12uM) and
2-guanidino-4H-1,3-benzothiazin-4-one (IC50=5.60uM, Ki=19.47uM)
displayed potent activities on xanthine oxidase inhibition. They
induced noncompetitive and mixed (non-competi tive-uncompective)
type inhibitions respectively, with respect to the substrate
xanthine. Rhodanine (IC50=121.40uM, Ki=206.23uM) also showed
moderate effects on xanthine oxidase inhibition, and induced
mixed (non-compective-uncompetitive) type inhibition of the
enzyme with respect to the substrate xanthine.
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