Ajmalicine
(Synonyms: 萝巴新,Raubasine) 目录号 : GC35272
A terpenoid indole alkaloid
Cas No.:483-04-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Ajmalicine is an terpenoid indole alkaloid that has been found in R. serpentina.1,2 It is an α1-adrenergic receptor antagonist, reducing the phenylephrine-induced pressor response in pithed rats when administered at doses ranging from 1 to 4 mg/kg.3 It also binds to α2A-, α2B-, α2C-, and α2D-adrenergic receptors (Kis = 8.2, 14.5, 5, and 289 nM, respectively).4 Ajmalicine, in combination with almitrine, improves hemodynamic and metabolic parameters following transient cerebral ischemia in dogs.5
1.Sharma, V., Chaudhary, S., Srivastava, S., et al.Characterization of variation and quantitative trait loci related to terpenoid indole alkaloid yield in a recombinant inbred line mapping population of Catharanthus roseusJ. Genet.91(1)49-69(2012) 2.Srivastava, A., Tripathi, A.K., Pandey, R., et al.Quantitative determination of reserpine, ajmaline, and ajmalicine in Rauvolfia serpentina by reversed-phase high-performance liquid chromatographyJ. Chromatogr. Sci.44(9)557-560(2006) 3.Demichel, P., Gomond, P., and Roquebert, J.α-Adrenoceptor blocking properties of raubasine in pithed ratsBr. J. Pharmacol.77(3)449-454(1982) 4.Ruffolo, R.R., Jr., Bondinell, W., and Hieble, J.P.α- and β-adrenoceptors: From the gene to the clinic. 2. Structure-activity relationships and therapeutic applicationsJ. Med. Chem.38(19)3681-3716(1995) 5.Cahn, R., and Cahn, J.Curative effect of an almitrine-raubasine combination in the postischemic syndrome following transient cerebral ischemia in dogsPharmacology36(3)156-165(1988)
| Cas No. | 483-04-5 | SDF | |
| 别名 | 萝巴新,Raubasine | ||
| Canonical SMILES | O=C(C1=CO[C@@H](C)[C@](CN2CC3)([H])[C@]1([H])C[C@@]2([H])C4=C3C5=CC=CC=C5N4)OC | ||
| 分子式 | C21H24N2O3 | 分子量 | 352.43 |
| 溶解度 | DMSO : 5.56 mg/mL (15.78 mM; ultrasonic and warming and heat to 60°C) | 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 | 2.8374 mL | 14.1872 mL | 28.3744 mL |
| 5 mM | 0.5675 mL | 2.8374 mL | 5.6749 mL |
| 10 mM | 0.2837 mL | 1.4187 mL | 2.8374 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。
Ajmalicine and Reserpine: Indole Alkaloids as Multi-Target Directed Ligands Towards Factors Implicated in Alzheimer's Disease
Molecules 2020 Apr 1;25(7):1609.PMID:32244635DOI:10.3390/molecules25071609.
Alzheimer's disease (AD) is a multifactorial disorder characterized by exponential loss of memory and cognitive deficit involving several disease modifying targets (amyloid beta, beta-secretase, monoaminoxidase-B, and cholinesterase). The present study explores multi-target directed ligand approach using secondary metabolite reserpine (RES) and Ajmalicine (AJM) obtained from Rauwolfia serpentina roots. Novel LCMS and HPLC methods were developed for identification and quantification of reserpine and Ajmalicine. In vitro enzyme inhibition assays were performed to evaluate anti-cholinesterase, β-site amyloid cleaving enzyme (BACE-1) inhibition and monoamine oxidase-B (MAO-B) inhibition, further analyzed with in silico analysis. Anti-amyloidogenic potential was studied using anti-aggregation studies along with TEM and circular dichroism (CD) analysis. In vitro neuroprotective potential against Aβ toxicity and anti-oxidative stress was demonstrated using PC12 cell cultures. Reserpine is a more potent dual cholinesterase inhibitor than Ajmalicine (IC50 values of 1.7 μM (AChE) and 2.8 μM (BuChE)). The anti-aggregation activity of reserpine (68%) was more than Ajmalicine (56%). Both compounds demonstrated neuroprotective activity against Aβ42 (92%) and H2O2 (93%) induced toxicity in PC12 cells against controls. Phytocompounds also inhibited MAO-B and BACE-1 enzymes in concentration dependent manner. Molecular docking studies indicated the strong binding of compounds to the catalytic site of targets. This novel study demonstrated that reserpine and Ajmalicine as a multi-target directed ligand that have disease modifying potential for amelioration of AD.
Construction of Ajmalicine and sanguinarine de novo biosynthetic pathways using stable integration sites in yeast
Biotechnol Bioeng 2022 May;119(5):1314-1326.PMID:35060115DOI:10.1002/bit.28040.
Yeast cell factories have been increasingly employed for producing plant-derived natural products. Unfortunately, the stability of plant natural product biosynthetic pathway genes, particularly when driven by the same sets of promoters and terminators, remains one of the biggest concerns for synthetic biology. Here we profile genomic loci flanked by essential genes as stable integration sites in a genome-wide manner, for stable maintenance of multigene biosynthetic pathways in yeast. We demonstrate the application of our yeast integration platform in the construction of sanguinarine (24 expression cassettes) and Ajmalicine (29 expression cassettes) de novo biosynthetic pathways for the first time. Moreover, we establish stable yeast cell factories that can produce 119.2 mg L-1 heteroyohimbine alkaloids (containing 61.4 mg L-1 Ajmalicine) in shake flasks, representing the highest titer of monoterpene indole alkaloids (MIAs) ever reported and promising the complete biosynthesis of other high-value MIAs (such as vinblastine) for biotechnological applications.
Ajmalicine production in methyl jasmonate-induced Catharanthus roseus cell cultures depends on Ca2+ level
Plant Cell Rep 2005 Dec;24(11):677-82.PMID:16094527DOI:10.1007/s00299-005-0026-0.
Cytosolic Ca(2+) and jasmonate mediate signals that induce defense responses in plants. In this study, the interaction between Ca(2+) and methyl jasmonate (MJ) in modulating defense responses was investigated by monitoring Ajmalicine production in Catharanthus roseus suspension cultures. C. roseus suspensions were treated with nine combinations of CaCl(2) (3, 23, and 43 mM) and MJ (0, 10, and 100 microM) on day 6 of growth. Increased Ca(2+) influx through the addition of extracellular CaCl(2) suppressed Ajmalicine production in MJ-induced cultures. The highest Ajmalicine production (4.75 mg/l) was observed when cells were treated with a low level of calcium (3 mM) combined with a high level of MJ (100 microM). In the presence of 3 mM CaCl(2) in the medium, the addition of Ca(2+) chelator EGTA (1, 2.5, and 5 mM) or Ca(2+) channel blocker verapamil (1, 10, and 50 muM) to MJ-induced (100 microM) cultures on day 6 also inhibited Ajmalicine production at higher levels of the Ca(2+) inhibitors. Hence, Ajmalicine production in MJ-induced C. roseus cultures depended on the intracellular Ca(2+) concentration and a low extracellular Ca(2+) concentration (3 mM) enhanced MJ-induced Ajmalicine production.
Engineering the MEP pathway enhanced Ajmalicine biosynthesis
Biotechnol Appl Biochem 2014 May-Jun;61(3):249-55.PMID:24237015DOI:10.1002/bab.1176.
The 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway genes encoding DXR and MECS from Taxus species and STR from Catharanthus roseus were used to genetically modify the Ajmalicine biosynthetic pathway in hairy root cultures of C. roseus. As expected, the STR-overexpressed root cultures showed twofold higher accumulation of Ajmalicine than the control. It was important to discover that overexpression of the single DXR or MECS gene from the MEP pathway also remarkably enhanced Ajmalicine biosynthesis in transgenic hairy root cultures, and this suggested that engineering the MEP pathway by overexpression of DXR or MECS promoted the metabolic flux into Ajmalicine biosynthesis. The transgenic hairy root cultures with co-overexpression of DXR and STR or MECS and STR had higher levels of Ajmalicine than those with overexpression of a single gene alone such as DXR, MECS, and STR. It could be concluded that transgenic hairy root cultures harboring both DXR/MECS and STR possessed an increased flux in the terpenoid indole alkaloid biosynthetic pathway that enhanced Ajmalicine yield, which was more efficient than cultures harboring only one of the three genes.
Ajmalicine and its Analogues Against AChE and BuChE for the Management of Alzheimer's Disease: An In-silico Study
Curr Pharm Des 2020;26(37):4808-4814.PMID:32264807DOI:10.2174/1381612826666200407161842.
Background: Alzheimer's disease (AD) is the most well-known reason for disability in persons aged greater than 65 years worldwide. AD influences the part of the brain that controls cognitive and non-cognitive functions. Objective: The study focuses on the screening of natural compounds for the inhibition of AChE and BuChE using a computational methodology. Methods: We performed a docking-based virtual screening utilizing the 3D structure of AChE and BuChE to search for potential inhibitors for AD. In this work, a screened inhibitor Ajmalicine similarity search was carried out against a natural products database (Super Natural II). Lipinski rule of five was carried out and docking studies were performed between ligands and enzyme using 'Autodock4.2'. Results: Two phytochemical compounds SN00288228 and SN00226692 were predicted for the inhibition of AChE and BuChE, respectively. The docking results revealed Ajmalicine, a prominent natural alkaloid, showing promising inhibitory potential against AChE and BuChE with the binding energy of -9.02 and -8.89 kcal/mole, respectively. However, SN00288228- AChE, and SN00226692-BuChE were found to have binding energy -9.88 and -9.54 kcal/mole, respectively. These selected phytochemical compounds showed better interactions in comparison to Ajmalicine with the target molecule. Conclusion: The current study verifies that SN00288228 and SN00226692 are more capable inhibitors of human AChE and BuChE as compared to Ajmalicine with reference to ΔG values.