Scoulerine
(Synonyms: 金黄紫堇碱,(-)-Scoulerine; Discretamine) 目录号 : GC39798
A benzylisoquinoline alkaloid with diverse biological activities
Cas No.:6451-73-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Scoulerine is a benzylisoquinoline alkaloid that has been found in C. cava and has diverse biological activities.1,2,3 It selectively binds to the dopamine D1 and D2 receptors (Kis = 22 and 214 nM, respectively) over the serotonin (5-HT) receptor subtypes 5-HT1A and 5-HT2A in HEK293 cells when used at a concentration of 10 ?M.1 Scoulerine inhibits proliferation in a panel of leukemia cell lines (IC50s = 2.7-6.5 ?M).2 It inhibits methamphetamine-induced conditioned place preference in mice when administered at a dose of 5 mg/kg.3
1.Sun, H., Zhu, L., Yang, H., et al.Asymmetric total synthesis and identification of tetrahydroprotoberberine derivatives as new antipsychotic agents possessing a dopamine D1, D2 and serotonin 5-HT1A multi-action profileBioorg. Med. Chem.21(4)856-868(2013) 2.Habartova, K., Havelek, R., Seifrtova, M., et al.Scoulerine affects microtubule structure, inhibits proliferation, arrests cell cycle and thus culminates in the apoptotic death of cancer cellsSci. Rep.8(1)4829(2018) 3.Mi, G., Gao, Y., Yan, H., et al.l-Scoulerine attenuates behavioural changes induced by methamphetamine in zebrafish and miceBehav. Brain Res.298(Pt A)97-104(2016)
| Cas No. | 6451-73-6 | SDF | |
| 别名 | 金黄紫堇碱,(-)-Scoulerine; Discretamine | ||
| Canonical SMILES | OC1=C(OC)C=C(CCN2CC3=C(O)C(OC)=CC=C3C[C@]24[H])C4=C1 | ||
| 分子式 | C19H21NO4 | 分子量 | 327.37 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.0546 mL | 15.2732 mL | 30.5465 mL |
| 5 mM | 0.6109 mL | 3.0546 mL | 6.1093 mL |
| 10 mM | 0.3055 mL | 1.5273 mL | 3.0546 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
The Phytochemical Scoulerine Inhibits Aurora Kinase Activity to Induce Mitotic and Cytokinetic Defects
J Nat Prod 2021 Aug 27;84(8):2312-2320.PMID:34406008DOI:10.1021/acs.jnatprod.1c00429.
To identify novel bioactive compounds, an image-based, cell culture screening of natural product extracts was conducted. Specifically, our screen was designed to identify phytochemicals that might phenocopy inhibition of the chromosomal passenger protein complex in eliciting mitotic and cytokinetic defects. A known alkaloid, Scoulerine, was identified from the rhizomes of the plant Corydalis decumbens as being able to elicit a transient mitotic arrest followed by either apoptosis induction or polyploidy. In examining the mitotic abnormality further, we observed that Scoulerine could elicit supernumerary centrosomes during mitosis, but not earlier in the cell cycle. The localization of NUMA1 at spindle poles was also inhibited, suggesting diminished potential for microtubule recruitment and spindle-pole focusing. Polyploid cells emerged subsequent to cytokinetic failure. The concentration required for Scoulerine to elicit all its cell division phenotypes was similar, and an examination of related compounds highlighted the requirement for proper positioning of a hydroxyl and a methoxy group about an aromatic ring for activity. Mechanistically, Scoulerine inhibited AURKB activity at concentrations that elicited supernumerary centrosomes and polyploidy. AURKA was only inhibited at higher concentrations, so AURKB inhibition is the likely mechanism by which Scoulerine elicited division defects. AURKB inhibition was never complete, so Scoulerine may be a suboptimal AURK inhibitor or work upstream of the chromosomal passenger protein complex to reduce AURKB activity. Scoulerine inhibited the viability of a variety of human cancer cell lines. Collectively, these findings uncover a previously unknown activity of Scoulerine that could facilitate targeting human cancers. Scoulerine, or a next-generation analogue, may be useful as a nontoxic component of combination therapies where inhibiting the chromosomal passenger protein complex is desired.
Scoulerine promotes cell viability reduction and apoptosis by activating ROS-dependent endoplasmic reticulum stress in colorectal cancer cells
Chem Biol Interact 2020 Aug 25;327:109184.PMID:32590070DOI:10.1016/j.cbi.2020.109184.
Scoulerine, an isoquinoline alkaloid isolated from Corydalis plants, has been reported to possess potent anti-proliferative and pro-apoptotic function in cancer cells. However, the effects and underlying mechanisms of Scoulerine on colorectal cancer (CRC) progression remain elusive. CCK-8 and LDH assays were used to evaluate cell viability. Apoptosis was assessed by flow cytometry analysis, caspase-3/7 activity assay, and Western blot analysis of Bax, Bcl-2 and cytochrome c (Cyt C) expression. Oxidative stress level was examined by measuring reactive oxygen species (ROS) and glutathione (GSH) contents and superoxide dismutase (SOD) activity. Endoplasmic reticulum (ER) stress activation was detected by Western blot analysis of glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) expression. Results showed that Scoulerine dose-dependently suppressed CRC cell viability. Scoulerine induced apoptosis and increased caspase-3/7 activity in CRC cells. Bax and cytosolic Cyt C expression was enhanced while Bcl-2 and mitochondrial Cyt C expression was reduced in scoulerine-treated CRC cells. Additionally, Scoulerine induced oxidative damage in CRC cells by increasing ROS generation and reducing GSH content and SOD activity. Scoulerine activated ER stress, as evidenced by the increased GRP78 and CHOP expression in CRC cells. Interestingly, blocking ROS production by ROS scavenger N-acetyl-cysteine (NAC) attenuated scoulerine-induced ER stress. Inhibition of ER stress by 4-phenyl butyric acid (4-PBA) abolished scoulerine-induced ROS generation in CRC cells. Blockage of ROS and ER stress attenuated scoulerine-induced cell viability reduction and apoptosis in CRC cells. In conclusion, Scoulerine promoted cell viability reduction and apoptosis by activating ROS-dependent ER stress in CRC cells.
Scoulerine affects microtubule structure, inhibits proliferation, arrests cell cycle and thus culminates in the apoptotic death of cancer cells
Sci Rep 2018 Mar 19;8(1):4829.PMID:29555944DOI:10.1038/s41598-018-22862-0.
Scoulerine is an isoquinoline alkaloid, which indicated promising suppression of cancer cells growth. However, the mode of action (MOA) remained unclear. Cytotoxic and antiproliferative properties were determined in this study. Scoulerine reduces the mitochondrial dehydrogenases activity of the evaluated leukemic cells with IC50 values ranging from 2.7 to 6.5 µM. The xCELLigence system revealed that Scoulerine exerted potent antiproliferative activity in lung, ovarian and breast carcinoma cell lines. Jurkat and MOLT-4 leukemic cells treated with Scoulerine were decreased in proliferation and viability. Scoulerine acted to inhibit proliferation through inducing G2 or M-phase cell cycle arrest, which correlates well with the observed breakdown of the microtubule network, increased Chk1 Ser345, Chk2 Thr68 and mitotic H3 Ser10 phosphorylation. Scoulerine was able to activate apoptosis, as determined by p53 upregulation, increase caspase activity, Annexin V and TUNEL labeling. Results highlight the potent antiproliferative and proapoptotic function of Scoulerine in cancer cells caused by its ability to interfere with the microtubule elements of the cytoskeleton, checkpoint kinase signaling and p53 proteins. This is the first study of the mechanism of Scoulerine at cellular and molecular level. Scoulerine is a potent antimitotic compound and that it merits further investigation as an anticancer drug.
Computational Prediction and Experimental Validation of the Unique Molecular Mode of Action of Scoulerine
Molecules 2022 Jun 21;27(13):3991.PMID:35807231DOI:10.3390/molecules27133991.
Scoulerine is a natural compound that is known to bind to tubulin and has anti-mitotic properties demonstrated in various cancer cells. Its molecular mode of action has not been precisely known. In this work, we perform computational prediction and experimental validation of the mode of action of Scoulerine. Based on the existing data in the Protein Data Bank (PDB) and using homology modeling, we create human tubulin structures corresponding to both free tubulin dimers and tubulin in a microtubule. We then perform docking of the optimized structure of Scoulerine and find the highest affinity binding sites located in both the free tubulin and in a microtubule. We conclude that binding in the vicinity of the colchicine binding site and near the laulimalide binding site are the most likely locations for Scoulerine interacting with tubulin. Thermophoresis assays using Scoulerine and tubulin in both free and polymerized form confirm these computational predictions. We conclude that Scoulerine exhibits a unique property of a dual mode of action with both microtubule stabilization and tubulin polymerization inhibition, both of which have similar affinity values.
Anti-inflammatory, Anti-bacterial and Anti-acetylcholinesterase Activities of two Isoquinoline Alkaloids-Scoulerine and Cheilanthifoline
Nat Prod Commun 2016 Dec;11(12):1801-1804.PMID:30508337doi
Corydalis plants containing isoquinoline alkaloids are reported to possess promising phamacological properties for the treatment of important diseases including cancer, inflammation, Alzheimer's disease and microbial infections. As part of a wider program investigating Bhutanese medicinal plants,.we have previously identified eight isoquinoline alkaloids from C. dubia. Out of these, we report here on two of the major alkaloids, Scoulerine (1) and cheilanthifoline (2) and their inhibitory activities against acetylcholinesterase (anti-AChE),-tumor necrosis factor alpha (anti TNF-α) and a bacteial strain, Helicobacterpylori. Both alkaloids showed weak anti TNF-α and antibacterial activities. However, the anti-AChE activity of Scoulerine (1) was promising as it-significantly inhibited AChE with a minimum inhibitory requirement (MIR) value of 0.0015 nmol, which was two-fold better than the reference drug, galanthamine (MIR value of 0.003 nmol). As there are limited.anti-Alzheimer's chemotherapeutics, Scoulerine (1) is worthy of further exploration, including lead optimization, structure-activity-relationship studies, analog development,.pharmacodynanics and in vivo animal studies.