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石蒜碱 | 476-28-8

中文名称
石蒜碱
中文别名
石蒜碱盐酸盐
英文名称
lycorine
英文别名
lycorine hydrochloride;LYC;(1S,17S,18S,19S)-5,7-dioxa-12-azapentacyclo[10.6.1.02,10.04,8.015,19]nonadeca-2,4(8),9,15-tetraene-17,18-diol
石蒜碱化学式
CAS
476-28-8
化学式
C16H17NO4
mdl
——
分子量
287.315
InChiKey
XGVJWXAYKUHDOO-DANNLKNASA-N
BEILSTEIN
——
EINECS
——
  • 物化性质
  • 计算性质
  • ADMET
  • 安全信息
  • SDS
  • 制备方法与用途
  • 上下游信息
  • 反应信息
  • 文献信息
  • 表征谱图
  • 同类化合物
  • 相关功能分类
  • 相关结构分类

物化性质

  • 熔点:
    253-255℃ (dec.)
  • 比旋光度:
    D16 -129° (c = 0.16 in 98% alc)
  • 沸点:
    429.61°C (rough estimate)
  • 密度:
    1.53
  • 溶解度:
    溶于氯仿、二氯甲烷、乙酸乙酯、DMSO、丙酮等。

计算性质

  • 辛醇/水分配系数(LogP):
    0
  • 重原子数:
    21
  • 可旋转键数:
    0
  • 环数:
    5.0
  • sp3杂化的碳原子比例:
    0.5
  • 拓扑面积:
    62.2
  • 氢给体数:
    2
  • 氢受体数:
    5

ADMET

代谢
对氧酶(PON1)是有机代谢的关键酶。PON1可以通过解使一些有机失活。PON1解几种有机磷杀虫剂以及神经毒剂(如梭曼、沙林和VX)的活性代谢物。PON1的多态性导致不同的酶平和这种酯酶的催化效率,这反过来表明不同个体可能更容易受到有机暴露的毒性影响。
Paraoxonase (PON1) is a key enzyme in the metabolism of organophosphates. PON1 can inactivate some organophosphates through hydrolysis. PON1 hydrolyzes the active metabolites in several organophosphates insecticides as well as, nerve agents such as soman, sarin, and VX. The presence of PON1 polymorphisms causes there to be different enzyme levels and catalytic efficiency of this esterase, which in turn suggests that different individuals may be more susceptible to the toxic effect of OP exposure.
来源:Toxin and Toxin Target Database (T3DB)
毒理性
  • 毒性总结
洋红素是一种胆碱酯酶乙酰胆碱酯酶(AChE)抑制剂胆碱酯酶抑制剂(或“抗胆碱酯酶”)抑制乙酰胆碱酯酶的作用。由于其基本功能,干扰乙酰胆碱酯酶作用的化学物质是强大的神经毒素,低剂量时会引起过度流涎和流泪,随后是肌肉痉挛,最终导致死亡。神经气体和许多用于杀虫剂的物质已被证明通过结合乙酰胆碱酯酶活性位点的丝氨酸,完全抑制该酶。乙酰胆碱酯酶分解神经递质乙酰胆碱,该递质在神经和肌肉接点处释放,以使肌肉或器官放松。乙酰胆碱酯酶抑制的结果是乙酰胆碱积聚并继续发挥作用,使得任何神经冲动不断传递,肌肉收缩不会停止。最常见的乙酰胆碱酯酶抑制剂之一是基于的化合物,它们被设计用来结合到酶的活性位点上。结构要求是一个带有两个亲脂性基团的原子,一个离去基团(如卤素或硫氰酸盐),以及一个末端的氧。
Lycorine is a cholinesterase or acetylcholinesterase (AChE) inhibitor. A cholinesterase inhibitor (or 'anticholinesterase') suppresses the action of acetylcholinesterase. Because of its essential function, chemicals that interfere with the action of acetylcholinesterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death. Nerve gases and many substances used in insecticides have been shown to act by binding a serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen.
来源:Toxin and Toxin Target Database (T3DB)
毒理性
  • 致癌物分类
对人类无致癌性(未列入国际癌症研究机构IARC清单)。
No indication of carcinogenicity to humans (not listed by IARC).
来源:Toxin and Toxin Target Database (T3DB)
毒理性
  • 健康影响
急性接触胆碱酯酶抑制剂可能会导致胆碱能危象,表现为严重的恶心/呕吐、流涎、出汗、心动过缓、低血压、晕厥和抽搐。肌肉无力可能性增加,如果呼吸肌受累,可能会导致死亡。在运动神经积累的乙酰胆碱会导致神经肌肉接头处烟碱受体的过度刺激。当这种情况发生时,可能会看到肌肉无力、疲劳、肌肉痉挛、肌束震颤和麻痹的症状。当自主神经节积累乙酰胆碱时,这会导致交感系统中烟碱受体的过度刺激。与此相关的症状是高血压和低血糖。由于乙酰胆碱积累而在中枢神经系统中过度刺激烟碱乙酰胆碱受体,会导致焦虑、头痛、抽搐、共济失调、呼吸和循环抑制、震颤、全身无力,甚至可能昏迷。当由于副交感乙酰胆碱受体上乙酰胆碱过多而导致毒蕈碱过度刺激时,可能会出现视力障碍、胸部紧绷、由于支气管收缩引起的喘息、支气管分泌物增加、唾液分泌增加、流泪、出汗、肠蠕动和排尿的症状。对于男性和女性的生育、生长和发育,已经特别将与有机农药暴露联系起来。关于生殖影响的大多数研究都是在农村地区使用杀虫剂杀虫剂的农民进行的。在女性中,月经周期紊乱、怀孕时间延长、自然流产、死产以及后代的一些发育效应与有机农药暴露有关。产前暴露与胎儿生长和发育受损有关。神经毒性效应也与人因接触有机农药而中毒引起的四种神经毒性效应有关:胆碱能综合症、中间综合症、有机诱导的迟发性多发性神经病(OPIDP)和慢性有机诱导的神经精神障碍(COPIND)。这些综合症在急性接触和慢性接触有机农药后出现。
Acute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Certain reproductive effects in fertility, growth, and development for males and females have been linked specifically to organophosphate pesticide exposure. Most of the research on reproductive effects has been conducted on farmers working with pesticides and insecticdes in rural areas. In females menstrual cycle disturbances, longer pregnancies, spontaneous abortions, stillbirths, and some developmental effects in offspring have been linked to organophosphate pesticide exposure. Prenatal exposure has been linked to impaired fetal growth and development. Neurotoxic effects have also been linked to poisoning with OP pesticides causing four neurotoxic effects in humans: cholinergic syndrome, intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP), and chronic organophosphate-induced neuropsychiatric disorder (COPIND). These syndromes result after acute and chronic exposure to OP pesticides.
来源:Toxin and Toxin Target Database (T3DB)
毒理性
  • 症状
低剂量暴露的症状包括过度流涎和眼泪。急性剂量症状包括严重恶心/呕吐、流涎、出汗、心动过缓、低血压、虚脱和抽搐。肌肉无力可能会逐渐加剧,如果呼吸肌肉受影响,可能会导致死亡。还可能出现高血压、低血糖、焦虑、头痛、震颤和共济失调。
Symptoms of low dose exposure include excessive salivation and eye-watering. Acute dose symptoms include severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Hypertension, hypoglycemia, anxiety, headache, tremor and ataxia may also result.
来源:Toxin and Toxin Target Database (T3DB)
毒理性
  • 暴露处理
如果已经摄入该化合物,应使用5%碳酸氢钠进行快速洗胃。对于皮肤接触,应用肥皂和清洗皮肤。如果化合物进入眼睛,应用大量等渗盐清洗。在严重情况下,应给予阿托品和/或普瑞洛辛。抗胆碱能药物作用是拮抗过量的乙酰胆碱并重新激活乙酰胆碱酯酶。阿托品可以与普瑞洛辛或其他吡啶盐(如三甲氧基盐或欧比多辛)联合使用作为解毒剂,尽管在至少两个荟萃分析中发现使用“-氧酸盐”没有益处,甚至可能有害。阿托品是一种毒蕈碱拮抗剂,因此可以阻断乙酰胆碱的外周作用。
If the compound has been ingested, rapid gastric lavage should be performed using 5% sodium bicarbonate. For skin contact, the skin should be washed with soap and water. If the compound has entered the eyes, they should be washed with large quantities of isotonic saline or water. In serious cases, atropine and/or pralidoxime should be administered. Anti-cholinergic drugs work to counteract the effects of excess acetylcholine and reactivate AChE. Atropine can be used as an antidote in conjunction with pralidoxime or other pyridinium oximes (such as trimedoxime or obidoxime), though the use of '-oximes' has been found to be of no benefit, or possibly harmful, in at least two meta-analyses. Atropine is a muscarinic antagonist, and thus blocks the action of acetylcholine peripherally.
来源:Toxin and Toxin Target Database (T3DB)

安全信息

  • 危险品标志:
    T
  • 安全说明:
    S45
  • 危险类别码:
    R25
  • WGK Germany:
    3
  • 危险品运输编号:
    UN 2811 6.1/PG 3
  • 储存条件:
    库房应保持通风、低温和干燥。

SDS

SDS:1c423e12100cbf9346ad7a72144ad1c6
查看

制备方法与用途

生物活性

Lycorine 是从眼科植物中提取的天然生物碱,是一种强效且具有口服活性的SCAP(SREBF chaperone)抑制剂,其Kd值为15.24 nM。它通过下调SCAP蛋白平而不改变其转录来发挥作用,同时也是黑色素瘤血管生成的有效抑制剂,并有潜力用于前列腺癌和代谢疾病的治疗研究。

靶点
  • Kd: 15.24 nM (SCAP)
体外研究

Lycorine 在多种前列腺癌(PCa)细胞系中以剂量依赖性方式抑制细胞增殖,IC50范围为5 μM至10 μM。它对PNT1A细胞的增殖几乎没有影响。

  • SCAP (SREBF chaperone)
    • SCAP 是一种ER到高尔基体运输蛋白,在形成与INSIG1(诱导基因1)复合物时会发生构象变化,从而调节SREBFs的功能。

Lycorine 还在多个方面抑制了SREBFs及其下游靶标VE-cadherin和Semaphorin 4D的表达。

体内研究

口服给予小鼠Lycorine(15 mg/kg或30 mg/kg,每日一次)可减轻脂肪积累和代谢综合征,增加脂肪酸的脂解和β氧化,并提高成熟SREBFs平,从而改善高脂饮食诱导的高血脂、肝脂肪变性和胰岛素抵抗。

化学性质

Lycorine 是一种棱形大结晶体,熔点为275-280℃(分解)。它溶于稀酸,微溶于醇和氯仿或石油醚,几乎可溶于和碱类,并对石蕊呈碱性反应。其盐酸盐为长针状晶体,熔点为217℃(分解),而带一分子结晶的Lycorine 盐酸盐熔点为206℃。

用途
  • 口服或皮下注射Lycorine 具有流涎、抑制心脏功能和增加气管分泌的作用,曾被用作祛痰剂。
  • Lycorine 还具有较强的催吐作用,效力比吐根碱强但不及阿相吗啡
  • 经氢化后生成的二氢石蒜碱对阿米巴痢疾有较强抑制效果且毒性较小,并已临床应用。
  • 内胺盐形式的Lycorine 在动物实验中表现出抗肿瘤活性。
生产方法

从石蒜(Lycoris radiata)等石蒜科植物鳞茎中提取Lycorine 。

类别

有毒物品

毒性分级

中毒

急性毒性
  • 口服:小鼠 LD50: 10700 毫克/公斤
  • 皮下注射:小鼠 LD50: 145 毫克/公斤
燃烧危险特性

可燃;燃烧时产生有毒氮氧化物烟雾

储运特性

库房通风,低温干燥保存

灭火剂

干粉、泡沫、砂土、二氧化碳、雾状

上下游信息

  • 上游原料
    中文名称 英文名称 CAS号 化学式 分子量
  • 下游产品
    中文名称 英文名称 CAS号 化学式 分子量
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反应信息

  • 作为反应物:
    描述:
    石蒜碱吡啶盐酸草酰氯二甲基亚砜 作用下, 以 甲醇二氯甲烷 为溶剂, 反应 19.5h, 生成 1-acetyl-2-oxolycorine
    参考文献:
    名称:
    从天然产物石蒜碱制备结构多样的化合物
    摘要:
    据报道,从天然产物石蒜碱中合成了 52 种化合物,突出显示了不同的交叉偶联和取代策略以及与芳基中间体反应引起的不寻常的环重排。
    DOI:
    10.1021/acs.orglett.8b02562
  • 作为产物:
    描述:
    1α-hydroxy-9,10-methanediyldioxy-galanth-2-en-7-one 在 lithium aluminium tetrahydride 、 间氯过氧苯甲酸 作用下, 以 四氢呋喃吡啶氯仿 为溶剂, 生成 石蒜碱
    参考文献:
    名称:
    Tsuda,Y. et al., Journal of the Chemical Society. Perkin transactions I, 1979, p. 1358 - 1363
    摘要:
    DOI:
点击查看最新优质反应信息

文献信息

  • 一种石蒜碱β-芳基丙烯酸酯衍生物及其制备方法和用途
    申请人:山东达因海洋生物制药股份有限公司
    公开号:CN113416199B
    公开(公告)日:2022-03-01
    本申请提供一种石蒜碱β‑芳基丙烯酸酯衍生物及其制备方法和应用。所述石蒜碱β‑芳基丙烯酸酯衍生物具有式I所示结构:其中,Ar为C6‑12芳烃或C3‑10芳杂环,所述的芳杂环中的杂原子选自N、O、S;R为Ar上的取代基,为单取代或多取代,R独立地选自氢、卤素、卤代C1‑6烷基、卤代C1‑6烷氧基、硝基、羟基、C1‑6烷基、C1‑6烷氧基、C2‑6链烯基氧基、C2‑6烯基、C3‑6环烷基、苯基。所述石蒜碱β‑芳基丙烯酸酯衍生物具有良好的抗肿瘤活性,具有较好的药用前景。
  • [EN] COMPOUNDS THAT INDUCE FERROPTIC CELL DEATH<br/>[FR] COMPOSÉS INDUISANT LA MORT CELLULAIRE FERROPTOTIQUE
    申请人:UNIV ILLINOIS
    公开号:WO2020210158A1
    公开(公告)日:2020-10-15
    The diterpene natural product pleuromutilin was subjected to reaction sequences focused on creating ring system diversity in few synthetic steps. This effort resulted in a collection of compounds with previously unreported ring systems, providing a novel set of structurally diverse and highly complex compounds suitable for screening in a variety of different settings. Biological evaluation identified the novel compound ferroptocide, a small molecule that rapidly and robustly induces ferroptotic death of cancer cells. Target identification efforts and CRISPR knockout studies reveal that ferroptocide is an inhibitor of thioredoxin, a key component of the antioxidant system in the cell. Ferroptocide positively modulates the immune system in a murine model of breast cancer and will be a useful tool to study the utility of pro-ferroptotic agents for treatment of cancer.
    萜类天然产物截短侧耳素经过一系列旨在通过少数合成步骤创造环系多样性的反应序列处理。这一努力产生了一批具有先前未报道环系的化合物,提供了一套结构多样且高度复杂的新化合物,适合在各种不同环境中进行筛选。生物学评估发现了一种新型化合物死亡素,这是一种小分子,能迅速且强有力地诱导癌细胞发生死亡。目标识别努力和CRISPR敲除研究表明,死亡素是一种氧还蛋白抑制剂,这是细胞抗氧化系统的一个关键组成部分。死亡素在乳腺癌的小鼠模型中正向调节免疫系统,并将成为研究促进死亡剂治疗癌症效用的有用工具。
  • TIOPRONIN PRODRUGS, PHARMACEUTICAL COMPOSITIONS THEREOF, AND METHODS OF USE
    申请人:Nguyen Mark Quang
    公开号:US20170129867A1
    公开(公告)日:2017-05-11
    Tiopronin prodrugs, pharmaceutical compositions comprising the tiopronin prodrugs, and methods of using tiopronin prodrugs and pharmaceutical compositions thereof for treating liver, kidney, lung, neurological, inflammatory, and autoimmune disorders including non-alcoholic steatohepatitis, Wilson's disease, cystinuria, irritable bowel disorder, ulcerative colitis, rheumatoid arthritis, chronic obstructive pulmonary disease, interstitial lung disease, asthma, cystic fibrosis, Parkinson's disease, and Huntington's disease.
    Tiopronin前药、包含Tiopronin前药的药物组合物,以及使用Tiopronin前药和药物组合物治疗肝脏、肾脏、肺部、神经学、炎症和自身免疫障碍的方法,包括非酒精性脂肪肝炎、威尔逊病、胱酸尿症、肠易激综合症、溃疡性结肠炎、类风湿性关节炎、慢性阻塞性肺病、间质性肺病、哮喘、囊性纤维化、帕森病和亨廷顿病。
  • [EN] CYSTEINE, N-ACETYLCYSTEINE AND PENICILLAMINE PRODRUGS, PHARMACEUTICAL COMPOSITIONS THEREOF, AND METHODS OF USE<br/>[FR] PROMÉDICAMENTS CYSTÉINE, N-ACÉTYLCYSTÉINE ET PÉNICILLAMINE, LEURS COMPOSITIONS PHARMACEUTIQUES, ET LEURS PROCÉDÉS D'UTILISATION
    申请人:NGUYEN MARK QUANG
    公开号:WO2018174839A1
    公开(公告)日:2018-09-27
    Cysteine, N-acetylcysteine, and penicillamine prodrugs, pharmaceutical compositions comprising the cysteine, N-acetylcysteine, and penicillamine prodrugs, and methods of using cysteine, N-acetylcysteine, and penicillamine prodrugs and pharmaceutical compositions thereof for treating liver, kidney, lung, neurological, inflammatory, and autoimmune disorders including paracetamol overdose, non-alcoholic steatohepatitis, Wilson's disease, cystinuria, irritable bowel disorder, ulcerative colitis, rheumatoid arthritis, chronic obstructive pulmonary disease, interstitial lung disease, asthma, cystic fibrosis, Parkinson's disease, and Huntington's disease.
    半胱酸、N-乙酰半胱酸和青霉胺前药,包括半胱酸、N-乙酰半胱酸和青霉胺前药的药物组合物,以及使用半胱酸、N-乙酰半胱酸和青霉胺前药及其药物组合物治疗肝脏、肾脏、肺部、神经系统、炎症性和自身免疫性疾病,包括对乙酚过量、非酒精性脂肪肝炎、威尔逊氏病、半胱酸尿症、肠易激综合征、溃疡性结肠炎、类风湿关节炎、慢性阻塞性肺病、间质性肺病、哮喘、囊性纤维化、帕森病和亨廷顿病的方法。
  • [EN] OXOBENZINDOLIZINOQUINOLINES AND USES THEREOF<br/>[FR] OXOBENZINDOLIZINOQUINOLÉINES ET LEURS UTILISATIONS
    申请人:PURDUE RESEARCH FOUNDATION
    公开号:WO2009140467A1
    公开(公告)日:2009-11-19
    The synthesis of aromathecins, substituted 12H-5,l la-diazadibenzo[b,h]fluoren- 11 -ones is described. Use of these cytotoxic compounds and pharmaceutical compositions containing them for the treatment of cancer is described. Two novel processes for the synthesis of this system and a series of 14-substituted aromathecins as novel cytotoxic, topoisomerase I poisons are described.
    描述了芳香烯合成,取代的12H-5,11a-二氮杂二苯并[b,h]-11-酮。描述了利用这些细胞毒性化合物和含有它们的药物组合物治疗癌症的方法。描述了合成这种体系的两种新方法和一系列14-取代芳香烯作为新型细胞毒性、拓扑异构酶I毒素。
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