德国春黄菊油 | 520-36-5

• 物质功能分类: 生物化工 - 天然产物
• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 中文名称: 德国春黄菊油
• 中文别名: 芹菜素；母菊油；芹黄素；芹菜素(5,7,4'-三羟基黄酮)；洋甘菊油；4',5,7-三羟基黄酮；芹黄素,4',5,7-三羟基黄酮,5,7,4'-三羟基黄酮；5,7,4'-三羟基黄酮；5,7-二羟基-2-(4-羟基苯基)-4H-苯并吡喃-4-酮
• 英文名称: 5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one
• 英文别名: apigenin；4',5,7-trihydroxyflavone；4′,5,7-trihydroxyflavone；5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one；5,7,4'-trihydroxyflavone；5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one；5,7,4’-trihydroxy flavone；5,7,4′-trihydroxyflavone
• CAS: 520-36-5；8002-66-2
• 化学式: C₁₅H₁₀O₅
• mdl: MFCD00006831
• 分子量: 270.241
• InChiKey: KZNIFHPLKGYRTM-UHFFFAOYSA-N

物化性质

• 熔点：
  >300 °C (lit.)
• 沸点：
  333.35°C (rough estimate)
• 密度：
  1.2319 (rough estimate)
• 溶解度：
  二甲基亚砜：27 毫克/毫升
• LogP：
  3.020
• 物理描述：
  Solid
• 颜色/状态：
  Yellow needles from aqueous pyridine
• 蒸汽压力：
  1.01X10-10 mm Hg at 25 °C (est)
• 分解：
  When heated to decomposition it emits acrid smoke and irritating fumes.
• 解离常数：
  pKa1 = 7.12 (phenol); pKa2 = 8.10 (phenol) (est)
• 碰撞截面：
  156 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  87
• 氢给体数：
  3
• 氢受体数：
  5

ADMET

代谢

对雄性Wistar大鼠口服给药芹菜素（200毫克）后，其尿液中提取的醚含有酚酸代谢物对羟基苯丙酸、对羟基肉桂酸和对羟基苯甲酸。未反应的芹菜素、部分鉴定的芹菜素葡萄糖苷酸和醚硫酸盐也被识别出来。除了对羟基苯甲酸和芹菜素结合物外，口服给药后在尿液中检测到的所有代谢物在体外也被大鼠肠道微生物在厌氧条件下形成……与此相反，在使用芹菜素局部治疗的SENCAR小鼠中未检测到这些代谢物。此外，从芹菜素处理的小鼠表皮提取物的高效液相色谱（HPLC）图谱中也没有观察到代谢物的证据……

Ether extracts of the urine of male Wistar rats administered apigenin (200 mg) orally contained the phenolic acid metabolites phydroxyphenylpropionic acid, p-hydroxycinnamic acid, and p-hydroxybenzoic acid. Unreacted apigenin, partially characterized apigenin glucuronides, and ethereal sulfates were also identified. With the exception of p-hydroxybenzoic acid and the apigenin conjugates, all of the metabolites detected in the urine after oral administration were also formed in vitro by rat intestinal microorganisms under anaerobic conditions ... In contrast, these metabolites were not detected in SENCAR mice treated topically with apigenin. Furthermore, no evidence of metabolites were observed from the HPLC profiles of epidermal extracts from apigenin-treated mice ...

来源:Hazardous Substances Data Bank (HSDB)

代谢

在大鼠肝脏Aroclor 1254诱导的微粒体中，芹菜素的主要体外代谢物被暂时鉴定为相应的3'-羟基化化合物，即木犀草素。芹菜素本身是白杨素（chrysin）的3'-羟基化代谢物...

The main in vitro metabolite of apigenin in rat liver Aroclor 1254-induced microsomes has been identified tentatively as the corresponding 3'-hydroxylated compound, luteolin. Apigenin itself is the 3'-hydroxylated metabolite of chrysin ...

来源:Hazardous Substances Data Bank (HSDB)

代谢

Apigenin 已知的人类代谢物包括 (2S,3S,4S,5R)-3,4,5-三羟基-6-[5-羟基-2-(4-羟基苯基)-4-氧代色酮-7-基]氧氧杂环己烷-2-羧酸。

Apigenin has known human metabolites that include (2S,3S,4S,5R)-3,4,5-Trihydroxy-6-[5-hydroxy-2-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxyoxane-2-carboxylic acid.

来源:NORMAN Suspect List Exchange

毒理性

• 致癌物分类

对人类不具有致癌性（未被国际癌症研究机构IARC列名）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 相互作用

这项研究调查了芹菜素对抗已知的遗传毒性物质，即苯并(a)芘（B(a)P）（口服125 mg/g）对瑞士白化小鼠的遗传毒性效应。B(a)P给药导致细胞色素P-450（CYP）、芳基烃羟化酶（AHH）和DNA链断裂（P < 0.001）的诱导，这些效应被芹菜素（口服2.5和5 mg/kg）以剂量依赖性方式抑制（P < 0.001）。B(a)P引起的还原型谷胱甘肽（GSH）、醌还原酶（QR）和谷胱甘肽-S-转移酶（GST）水平降低也被证明可以通过芹菜素预处理恢复（P < 0.001）。同时，DNA链断裂和体内DNA损伤显著且剂量依赖性地减少（P < 0.001），这为调节组中DNA完整性的恢复提供了一些见解。这些结果强烈支持芹菜素对B(a)P诱导毒性的保护作用。

... This study ... investigated the anti-genotoxic effects of apigenin against a known genotoxicant, benzo(a)pyrene (B(a)P) (125 mg/g orally) toxicity in Swiss albino mice. B(a)P administration led to induction of cytochrome P-450 (CYP), aryl hydrocarbon hydroxylase (AHH) and DNA strand breaks (P < 0.001), which was suppressed by apigenin (2.5 and 5 mg/kg orally) dose dependently (P < 0.001). B(a)P-induced depletion in the level of reduced glutathione (GSH), quinone reductase (QR) and glutathione-S-transferase (GST) was also shown to be restored by apigenin pre-treatment (P < 0.001). A simultaneous significant and dose-dependent reduction was noted in DNA strand breaks and in-vivo DNA damage (P < 0.001), which gives some insight into restoration of DNA integrity in modulator groups. These results strongly support the protective nature of apigenin against B(a)P-induced toxicity.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

Apigenin (0.01微摩尔)显著增加了MC3T3-E1细胞的生长，并导致细胞中碱性磷酸酶(ALP)活性和胶原含量的显著升高(P < 0.05)。当存在10^-6 M环己亚胺和10^-6 M他莫昔芬时，芹菜素增加ALP活性和胶原含量的作用被完全阻止，这表明芹菜素的作用源于新合成的蛋白质组分，可能与雌激素作用有关。

Apigenin (0.01 uM) significantly increased the growth of MC3T3-E1 cells and caused a significant elevation of alkaline phosphatase (ALP) activity and collagen content in the cells (P < 0.05). The effect of apigenin in increasing ALP activity and collagen content was completely prevented by the presence of 10-6 M cycloheximide and 10-6 M tamoxifen, suggesting that apigenin's effect results from a newly synthesized protein component and might be partly involved in estrogen action.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

研究了芹菜素对阿佐塞米（azoxymethane）诱导的肠腺癌在雄性Wistar大鼠中通过bombesin增强的腹膜转移发展的影响。从实验开始，大鼠每周接受阿佐塞米（7.4 mg/kg体重）的皮下注射，持续10周，每隔一天皮下注射bombesin（40 ug/kg体重），从第16周开始，每隔一天皮下注射芹菜素（0.75或1.5 mg/kg体重），直到实验结束的第45周。Bombesin显著增加了在第45周肠肿瘤的发生率和癌细胞向腹膜的转移。它还显著增加了肠道癌症的标记指数。尽管与bombesin联合使用时，无论是高剂量还是低剂量的芹菜素对bombesin增强的肠癌发生几乎没有影响，包括位置、组织学类型、浸润深度、浸润性生长模式和标记指数，但发现它显著减少了癌症转移的发生率。芹菜素显著减少了由bombesin增强的腺癌对淋巴管的侵犯。体外实验表明，芹菜素抑制了bombesin增强的丝裂原活化蛋白激酶（MAPK）的磷酸化，但对基质金属蛋白酶（MMP）-9的表达没有影响。

The effect of ... apigenin on the development of bombesin-enhanced peritoneal metastasis from intestinal adenocarcinomas induced by azoxymethane was investigated in male Wistar rats. From the start of the experiment, rats were given weekly sc injections of azoxymethane (7.4 mg/kg body weight) for 10 weeks and sc injection of bombesin (40 ug/kg body weight) every other day, and from week 16, sc injections of apigenin (0.75 or 1.5 mg/kg body weight) every other day until the end of the experiment in week 45. Bombesin significantly increased the incidence of intestinal tumors and cancer metastasis to the peritoneum in week 45. It also significantly increased the labeling index of intestinal cancers. Although administration of apigenin at either dose with bombesin had little or no effect on the enhancement of intestinal carcinogenesis by bombesin, the location, histologic type, depth of involvement, infiltrating growth patterns and labeling index, it was found to decrease significantly the incidence of cancer metastasis. Apigenin significantly decreased the incidence of lymphatic vessel invasion of adenocarcinomas, which was enhanced by bombesin. In vitro experiments revealed that apigenin inhibited bombesin-enhanced phosphorylation of mitogen-activated protein kinase (MAPK), but not matrix metalloprotease (MMP)-9 expression.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 立即急救：确保已经进行了充分的中和。如果患者停止呼吸，请开始人工呼吸，最好使用需求阀复苏器、球囊阀面罩设备或口袋面罩，按训练操作。如有必要，执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果患者呕吐，让患者向前倾或将其置于左侧（如果可能的话，头部向下），以保持呼吸道畅通，防止吸入。保持患者安静，维持正常体温。寻求医疗帮助。 /毒物A和B/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

四小时后，给予黄酮苷提取物（相当于0.942毫克苷元）灌胃后，在大鼠的胃腔和胃壁、小肠腔以及盲肠腔和壁中观察到了芹菜素的苷元。胃壁中存在苷的证据表明，黄酮类的吸收并不需要其苷元的参与。在研究条件下，未检测到芹菜素的肾排泄...

Four hours after administration of a flavonoid glycoside extract (corresponding to 0.942 mg aglycones) by gavage, the aglycone of apigenin was observed in the lumen and the wall of the stomach, in the lumen of the small intestine and in the lumen and wall of the cecum in Wistar rats. The evidence of glycosides in the stomach wall suggested that the absorption of flavonoids did not require the presence of their aglycones. Under the study conditions, no renal excretion of apigenin was detected ...

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

芹菜素（Apigenin）在人类摄入欧芹（Petroselinum crispum）后似乎可以被吸收。在一项随机交叉研究中，连续两周的干预期间，十四名志愿者摄入了含有20克欧芹的饮食。在摄入欧芹期间（20.7至5727.3克/24小时），尿液中芹菜素的排泄量显著高于基础饮食期间（0至1571.7克/24小时）（P < 0.05）。芹菜素的半衰期计算为大约12小时。观察到芹菜素的生物利用度和排泄存在显著个体差异...

Apigenin appears to be absorbable by humans after intake of parsley (Petroselinum crispum). In a randomized crossover study with two one-week intervention periods in succession, fourteen volunteers consumed a diet that included 20 g parsley. The urinary excretion of apigenin was significantly higher (P < 0.05) during the intervention with parsley (20.7 to 5727.3 g/24 hr) than during the basic diet (0 to 1571.7 g/24 hr). The half-life for apigenin was calculated to be on the order of 12 hr. Significant individual variation in the bioavailability and excretion of apigenin was observed ...

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

11名健康受试者（5名女性，6名男性）年龄在23至41岁之间，平均体重指数为23.9 ± 4.1 kg/m²参加了这项研究。在接受了不含芹菜素和木犀草素的饮食后，每公斤体重服用了一剂2克漂白芹叶（相当于65.8 ± 15.5微摩尔芹菜素）。在服用芹叶后0、4、6、7、8、9、10、11和28小时采集血液样本，并收集24小时的尿液样本...平均而言，7.2 ± 1.3小时后达到最高芹菜素血浆浓度127 ± 81纳米摩尔/升，受试者之间的变异范围较大。所有参与者在服用大剂量后，血浆芹菜素浓度上升，并在28小时内降至检测限以下（2.3纳米摩尔/升）。24小时尿液中芹菜素的平均含量为144 ± 110纳米摩尔/24小时，相当于摄入剂量的0.22 ± 0.16%。这种黄烷酮可以在红细胞中检测到，但没有显示出剂量反应特性。

... Eleven healthy subjects (5 women, 6 men) in the age range of 23 to 41 years and with an average body mass index of 23.9 + or - 4.1 kg/sq m took part in this study. After an apigenin- and luteolin-free diet, a single oral bolus of 2 g blanched parsley (corresponding to 65.8 + or - 15.5 umol apigenin) per kilogram body weight was consumed. Blood samples were taken at 0, 4, 6, 7, 8, 9, 10, 11 and 28 hr after parsley consumption and 24-hour urine samples were collected ... On average, a maximum apigenin plasma concentration of 127 + or - 81 nmol/L was reached after 7.2 + or - 1.3 hr with a high range of variation between subjects. For all participants, plasma apigenin concentration rose after bolus ingestion and fell within 28 hr under the detection limit (2.3 nmol/L). The average apigenin content in 24-hour urine was 144 + or - 110 nmol/24 hr corresponding to 0.22 + or - 0.16% of the ingested dose. The flavone could be detected in red blood cells without showing dose-response characteristics.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

本文展示了在大鼠单次口服菊花提取物（CME）(200 mg/kg)后，对木犀草素和芹菜素吸收和排泄的研究。通过用盐酸或β-葡萄糖醛酸酶/硫酸酯酶去结合后，用高效液相色谱法测量血浆、尿液、粪便和胆汁中的木犀草素和芹菜素水平。结果显示，木犀草素和芹菜素在给药后1.1小时和3.9小时分别达到血浆浓度最高峰值。木犀草素和芹菜素的血药浓度-时间曲线下面积（AUC）分别为23.03和237.6微克·小时/毫升。木犀草素和芹菜素的总回收剂量分别为37.9%(尿液6.6%; 粪便31.3%)和45.2%(尿液16.6%; 粪便28.6%)。胆汁中累积排出的木犀草素和芹菜素分别占剂量的2.05%和6.34%。所有结果表明，在大鼠中，芹菜素可能比木犀草素更有效地被吸收，并且这两种黄酮类化合物都具有缓慢的消除相和快速的吸收，因此可以假设这两种化合物在体内可能会积累。

... The present paper shows the study of the absorption and excretion of luteolin and apigenin in rats after a single oral dose of Chrysanthemum morifolium extract (CME) (200 mg/kg). The levels of luteolin and apigenin in plasma, urine, feces, and bile were measured by HPLC after deconjugation with hydrochloric acid or beta-glucuronidase/sulfatase. The results showed that the plasma concentrations of luteolin and apigenin reached the highest peak level at 1.1 and 3.9 hr after dosing, respectively. The area under the concentration-time curves (AUC) for luteolin and apigenin were 23.03 and 237.6 ug h/mL, respectively. The total recovery of the dose was 37.9% (6.6% in urine; 31.3% in feces) for luteolin and 45.2% (16.6% in urine; 28.6% in feces) for apigenin. The cumulative luteolin and apigenin excreted in the bile was 2.05% and 6.34% of the dose, respectively. All of the results suggest apigenin may be absorbed more efficiently than luteolin in CME in rats, and both luteolin and apigenin have a slow elimination phase, with a quick absorption, so a possible accumulation of the two flavonoids in the body can be hypothesized.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在给大鼠单次口服放射性标记芹菜素后，10天内尿液中回收了51.0%的放射性，粪便中12.0%，血液中1.2%，肾脏中0.4%，肠道中9.4%，肝脏中1.2%，其余部分中24.8%。在通过尿液排出途径消除的化合物性质方面存在性别差异：未成熟雄性和雌性大鼠以及成熟雌性大鼠排出的芹菜素单葡萄糖苷酸结合物的百分比高于芹菜素单硫酸盐结合物（分别为10.0至31.6%对2.0至3.6%）。成熟雄性大鼠以相反的比例排出相同的化合物（分别为4.9%和13.9%）。口服给药后仅24小时血液中就出现了放射性。血液动力学显示消除半衰期长（91.8小时），分布体积为259 mL，血浆清除率为1.95 mL/小时。从这些实验中计算出的所有参数都表明芹菜素的代谢缓慢，吸收和消除阶段都较慢。因此，可以假设这种黄酮类化合物在体内可能积累。

After a single oral administration of radiolabeled apigenin /to rats/, 51.0% of radioactivity was recovered in urine, 12.0% in feces, 1.2% in the blood, 0.4% in the kidneys, 9.4% in the intestine, 1.2% in the liver, and 24.8% in the rest of the body within 10 days. Sex differences appear with regard to the nature of compounds eliminated via the urinary route: immature male and female rats, like mature female rats, excreted a higher percentage of the mono-glucuronoconjugate of apigenin than the mono-sulfoconjugate of apigenin (10.0 to 31.6% versus 2.0 to 3.6%, respectively). Mature male rats excreted the same compounds in an inverse ratio (4.9% and 13.9%, respectively). Radioactivity appeared in the blood only 24 hr after oral administration. Blood kinetics showed a high elimination half-time (91.8 hr), a distribution volume of 259 mL, and a plasmatic clearance of 1.95 mL/hr. All of the parameters calculated from these experiments suggested a slow metabolism of apigenin, with a slow absorption and a slow elimination phase. Thus, a possible accumulation of this flavonoid in the body can be hypothesized.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26,S36
• 危险类别码：
  R36/37/38
• WGK Germany：
  3
• 海关编码：
  2942000000
• 危险品运输编号：
  OTH
• RTECS号：
  LK9276000
• 危险标志：
  GHS07
• 危险性描述：
  H315,H319,H335
• 危险性防范说明：
  P261,P305 + P351 + P338

制备方法与用途

芹菜素简介

芹菜素是一种生物类黄酮化合物，可以在多种植物和草药中找到。在甘菊茶中含量特别丰富，并且在高剂量服用时能够起到减轻焦虑的作用。在更高剂量下，它还具有镇静效果。

理化性质

芹菜素为黄色针状结晶（吡啶水溶液），熔点约为345℃～350℃。几乎不溶于水，易溶于热乙醇，并可溶解于稀氢氧化钾(KOH)溶液中。它具有利尿、调节血压、抗菌和消炎等作用。

植物来源

芹菜素是一种天然存在的黄酮类化合物，主要存在于多种植物中，尤其是伞形科植物旱芹。其他如洋甘菊、蜜蜂花、紫苏、马鞭草及西洋蓍草也含有该成分。洋甘菊原产于英国，在德国、法国和摩洛哥等地也有种植。罗马洋甘菊与德国洋甘菊具有相似特征：约30公分高，中心黄色，花瓣白色，叶片略带毛绒感。洋甘菊有助于改善睡眠质量，缓解炎症及疼痛症状，并能减轻神经性皮肤瘙痒引起的失眠。中国也广泛栽培用于药用和制茶，日常凉茶的成分中常含有芹菜素，主要来自母菊洋甘菊干花。

信息由Chemicalbook的晓楠编辑整理。

生物活性与药理作用

芹菜素独特的分子结构赋予了其多种生理效应及生物学特性。它是天然抗氧化剂，具有降血压、舒张血管、预防动脉粥样硬化和抑制肿瘤等作用。与其他黄酮类物质相比（如槲皮素和山奈黄酮），芹菜素具有低毒性和无诱变性等特点，在医药和食品行业中都有一定应用。

然而，由于其水溶性较差且肠道吸收率较低，导致口服生物利用度和体内活性都相对有限，限制了其在某些方面的广泛应用。

化学性质

芹菜素几乎不溶于水，但能部分溶解于热乙醇，并可溶于稀氢氧化钾(KOH)溶液。它源自伞形科植物旱芹（Apium graveolens L. var. dulce DC）。

用途

作为一种黄酮类化合物，芹菜素能够捕获细胞周期的G2/M期并抑制细胞扩增。通过阻断细胞周期和诱导凋亡来抑制生长似乎与p53基因的表达有关。此外，它还能抑制蛋白激酶C，并通过这一途径抑制由PMA介导的肿瘤促进作用。研究表明芹菜素还能够抑制拓扑异构酶Ⅰ催化的脱氧核糖核酸再连接并增强间隙连接细胞间的通讯。

分类

有毒物质

刺激数据

轻微过敏性

可燃性危险特性

热分解，产生辛辣刺激烟雾

储运特性

库房需低温通风干燥保存

灭火剂

水、二氧化碳、泡沫、干粉

反应信息

• 作为反应物：
  描述：

  德国春黄菊油 在 Agrocybe aegerita peroxygenase 、 双氧水 、 维生素 C 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 以42%的产率得到野黄芩素
  参考文献：
  名称：

  芳香族过氧化酶对不同类黄酮的区域选择性羟化作用

  摘要：

  芳香过氧化物酶是选择性氧化多种有机化合物的细胞外真菌生物催化剂。我们发现，真菌的过氧柱状田头菇（AAE APO）催化ħ 2 ö 2依赖性多样黄酮的羟基化。反应进行迅速并区域选择性地产生优选的单羟基化产物，例如从黄烷酮，芹菜素，木犀草素，黄酮以及黄豆苷元，槲皮素，山奈酚和染料木黄酮。除了羟化，Ø充分甲氧基蜜橘素-demethylation被催化AAEAPO。该酶仅对槲皮素糖苷芦丁缺乏活性，这可能是由于庞大的糖取代基的空间位阻所致。机理研究表明，在羟基化过程中存在环氧化物中间体，并将H 2 O 2衍生的氧掺入反应产物中。我们的结果提出了真菌过氧合酶可能用于多功能，成本有效且可扩展的类黄酮代谢物合成的可能性。

  DOI：

  10.1016/j.tet.2011.05.008
• 作为产物：
  描述：

  黄酮 在 吡啶盐酸盐 作用下， 生成 德国春黄菊油
  参考文献：
  名称：

  Flavonoid glycosides of Artemisia monosperma and A. herba-alba

  摘要：

  DOI：

  10.1016/s0031-9422(00)80845-6
• 作为试剂：
  描述：

  谷胱甘肽 在 horseradish peroxidase type VI 德国春黄菊油 、 双氧水 、 三羟甲基氨基甲烷盐酸盐 作用下， 生成 L-谷胱甘肽 (氧化型)
  参考文献：
  名称：

  Glutathione-Dependent Generation of Reactive Oxygen Species by the Peroxidase-Catalyzed Redox Cycling of Flavonoids

  摘要：

  Catalytic concentrations of apigenin (a flavone containing a phenol B ring) and naringin or naringenin (flavanones containing a phenol B ring) caused extensive GSH oxidation at a physiological pH in the presence of peroxidase. Only catalytic H2O2 concentrations were required, indicating a redox cycling mechanism that generated H2O2 was involved. Extensive oxygen uptake ensued, the extent of which was proportional to the extent of GSH oxidation to GSSG and was markedly increased by superoxide dismutase. These results suggest that prooxidant phenoxyl radicals formed by these flavonoids co-oxidized GSH to form thiyl radicals which activated oxygen. GSH also prevented the peroxidase-catalyzed oxidative destruction of these flavonoids which suggests that phenoxyl radicals initiated the oxidative destruction. This is the first time that a group of flavonoids have been identified as prooxidants independent of autoxidation reactions catalyzed by the transition metal ions Fe3+, Fe2+, Mn2+, and CU2+.

  DOI：

  10.1021/tx980271b

文献信息

• [EN] ALANINE-BASED MODULATORS OF PROTEOLYSIS AND ASSOCIATED METHODS OF USE<br/>[FR] MODULATEURS DE PROTÉOLYSE À BASE D'ALANINE ET PROCÉDÉS D'UTILISATION ASSOCIÉS
  申请人：ARVINAS INC

  公开号：WO2017011590A1

  公开（公告）日：2017-01-19

  The description relates to inhibitors of Apoptosis Proteins (TAPs) binding compounds, including Afunctional compounds comprising the same, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the description provides compounds, which contain on one end a ligand which binds to the IAP E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type.

  描述涉及抑制凋亡蛋白（TAPs）结合化合物，包括包含相同的A功能化合物，这些化合物作为靶向泛素化的调节剂发挥作用，特别是根据本发明的双功能化合物抑制各种多肽和其他蛋白质的化合物。具体而言，描述提供了一端含有结合到IAP E3泛素连接酶的配体，另一端含有结合到靶蛋白的基团的化合物，使得靶蛋白靠近泛素连接酶以促使该蛋白的降解（和抑制）。可以合成化合物，表现出与几乎任何类型的靶向多肽的降解/抑制一致的广泛药理活性。
• [EN] AMINE-LINKED C3-GLUTARIMIDE DEGRONIMERS FOR TARGET PROTEIN DEGRADATION<br/>[FR] DÉGRONIMÈRES DE C3-GLUTARIMIDE LIÉS À UNE AMINE POUR LA DÉGRADATION DE PROTÉINES CIBLES
  申请人：C4 THERAPEUTICS INC

  公开号：WO2017197051A1

  公开（公告）日：2017-11-16

  This invention provides amine-linked C3-glutarimide Degronimers and Degrons for therapeutic applications as described further herein, and methods of use and compositions thereof as well as methods for their preparation.

  这项发明提供了胺连接的C3-戊二酰亚胺Degronimers和Degrons，用于治疗应用，如本文进一步描述的，以及它们的使用方法、组合物以及它们的制备方法。
• Curcumin analogs with anti-tumor and anti-angiogenic properties
  申请人：——

  公开号：US20020019382A1

  公开（公告）日：2002-02-14

  The present invention is directed to curcumin analogs exhibiting anti-tumor and anti-angiogenic properties, pharmaceutical formulations including such compounds and methods of using such compounds.

  本发明涉及表现出抗肿瘤和抗血管生成特性的姜黄素类似物，包括这些化合物的药物配方以及使用这些化合物的方法。
• Accurate Prediction of Glucuronidation of Structurally Diverse Phenolics by Human UGT1A9 Using Combined Experimental and In Silico Approaches
  作者：Baojian Wu、Xiaoqiang Wang、Shuxing Zhang、Ming Hu

  DOI：10.1007/s11095-012-0666-z

  日期：2012.6

  Catalytic selectivity of human UGT1A9, an important membrane-bound enzyme catalyzing glucuronidation of xenobiotics, was determined experimentally using 145 phenolics and analyzed by 3D-QSAR methods. Catalytic efficiency of UGT1A9 was determined by kinetic profiling. Quantitative structure activity relationships were analyzed using CoMFA and CoMSIA techniques. Molecular alignment of substrate structures was made by superimposing the glucuronidation site and its adjacent aromatic ring to achieve maximal steric overlap. For a substrate with multiple active glucuronidation sites, each site was considered a separate substrate. 3D-QSAR analyses produced statistically reliable models with good predictive power (CoMFA: q2 = 0.548, r2 = 0.949, r pred 2  = 0.775; CoMSIA: q2 = 0.579, r2 = 0.876, r pred 2  = 0.700). Contour coefficient maps were applied to elucidate structural features among substrates that are responsible for selectivity differences. Contour coefficient maps were overlaid in the catalytic pocket of a homology model of UGT1A9, enabling identification of the UGT1A9 catalytic pocket with a high degree of confidence. CoMFA/CoMSIA models can predict substrate selectivity and in vitro clearance of UGT1A9. Our findings also provide a possible molecular basis for understanding UGT1A9 functions and substrate selectivity.

  通过实验使用145种酚类化合物，并通过3D-QSAR方法分析，确定了人UGT1A9的催化选择性。UGT1A9是一种重要的膜结合酶，催化外源性物质的葡糖醛酸化反应。通过动力学分析确定了UGT1A9的催化效率。使用CoMFA和CoMSIA技术分析了定量结构活性关系。通过将葡糖醛酸化位点及其相邻的芳香环重叠，实现了底物结构的最大立体重叠。对于具有多个活性葡糖醛酸化位点的底物，每个位点被视为单独的底物。3D-QSAR分析产生了统计上可靠的模型，具有良好的预测能力（CoMFA：q2=0.548，r2=0.949，r pred 2=0.775；CoMSIA：q2=0.579，r2=0.876，r pred 2=0.700）。通过轮廓系数图阐明了底物中负责选择性差异的结构特征。将轮廓系数图叠加在UGT1A9的同源模型的催化口袋中，能够高度自信地识别UGT1A9的催化口袋。CoMFA/CoMSIA模型可以预测底物的选择性和UGT1A9的体外清除率。我们的发现还提供了理解UGT1A9功能和底物选择性的可能分子基础。
• [EN] MACROMOLECULAR PRODRUG-BASED THERMOSENSITIVE INJECTABLE GEL AS A NOVEL DRUG DELIVERY PLATFORM<br/>[FR] GEL INJECTABLE THERMOSENSIBLE À BASE DE PRO-MÉDICAMENT MACROMOLÉCULAIRE EN TANT QUE NOUVELLE PLATEFORME D'ADMINISTRATION DE MÉDICAMENT
  申请人：UNIV NEBRASKA

  公开号：WO2020087057A1

  公开（公告）日：2020-04-30

  This application discloses prodrug-based thermosensitive gel ("ProGel") comprised of conjugates of dmg molecules with water-soluble polymeric carriers, which are capable of controlled release of the dmg molecules into the tissue of a subject. Use of the ProGel-Drug conjugates for treatment of various diseases or disorders and methods of preparing them are also disclosed.

  这种应用披露了基于前药的热敏凝胶（“ProGel”），由dmg分子与水溶性聚合物载体的共轭物组成，能够将dmg分子控制释放到受试者的组织中。还披露了将ProGel-药物共轭物用于治疗各种疾病或紊乱的方法以及制备它们的方法。

表征谱图