Manzamine A
(Synonyms: Keramamine A) 目录号 : GC44126
A β-carboline alkaloid
Cas No.:104196-68-1
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
Manzamine A is a β-carboline alkaloid with diverse activities that has been found in marine sponges, including X. ashmorica. It is an inhibitor of glycogen synthase kinase 3β (GSK3β) and cyclin-dependent kinase 5 (CDK5; IC50s = 10.2 and 1.5 μM, respectively). It inhibits the growth of L5178y mouse lymphoma cells with an ED50 value of 1.8 μg/mL. In an agar diffusion assay, manzamine A inhibits the growth of B. subtilis and S. aureus, but not E. coli bacteria. It reduces the reverse transcriptase (RT) activity in supernatant from HIV-1-infected peripheral blood mononuclear cells (PBMCs; EC50 = 4.2 μM). In vivo, manzamine A (100 μmol/kg, i.p.) has antimalarial activity and reduces the amount of P. berghei in infected mice by over 90% relative to the control. Manzamine A (132 ppm) inhibits the growth of S. littoralis larva by 80% when added to the larval diet.
| Cas No. | 104196-68-1 | SDF | |
| 别名 | Keramamine A | ||
| Canonical SMILES | [H][C@@]1(N2CCCC/C=C\1)C[C@@]3(C4)[C@]2([H])[C@]5(O)CC/C=C/CCCC[N@@]4CC[C@@]3([H])C(C6=C(NC7=C8C=CC=C7)C8=CC=N6)=C5 | ||
| 分子式 | C36H44N4O | 分子量 | 548.8 |
| 溶解度 | DMSO : 10 mg/mL (18.22 mM; Need ultrasonic) | 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 | 1.8222 mL | 9.1108 mL | 18.2216 mL |
| 5 mM | 0.3644 mL | 1.8222 mL | 3.6443 mL |
| 10 mM | 0.1822 mL | 0.9111 mL | 1.8222 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。
Manzamine-A Alters In Vitro Calvarial Osteoblast Function
Mar Drugs 2022 Oct 19;20(10):647.PMID:36286470DOI:10.3390/md20100647.
Manzamine-A is a marine-derived alkaloid which has anti-viral and anti-proliferative properties and is currently being investigated for its efficacy in the treatment of certain viruses (malaria, herpes, HIV-1) and cancers (breast, cervical, colorectal). Manzamine-A has been found to exert effects via modulation of SIX1 gene expression, a gene critical to craniofacial development via the WNT, NOTCH, and PI3K/AKT pathways. To date little work has focused on Manzamine-A and how its use may affect bone. We hypothesize that Manzamine-A, through SIX1, alters bone cell activity. Here, we assessed the effects of Manzamine-A on cells that are responsible for the generation of bone, pre-osteoblasts and osteoblasts. PCR, qrtPCR, MTS cell viability, Caspase 3/7, and functional assays were used to test the effects of Manzamine-A on these cells. Our data suggests Six1 is highly expressed in osteoblasts and their progenitors. Further, osteoblast progenitors and osteoblasts exhibit great sensitivity to Manzamine-A treatment exhibited by a significant decrease in cell viability, increase in cellular apoptosis, and decrease in alkaline phosphatase activity. In silico binding experiment showed that Manzamine A potential as an inhibitor of cell proliferation and survival proteins, i.e., Iκb, JAK2, AKT, PKC, FAK, and Bcl-2. Overall, our data suggests Manzamine-A may have great effects on bone health overall and may disrupt skeletal development, homeostasis, and repair.
Manzamine A Exerts Anticancer Activity against Human Colorectal Cancer Cells
Mar Drugs 2018 Jul 29;16(8):252.PMID:30060617DOI:10.3390/md16080252.
Marine sponges are known to produce numerous bioactive secondary metabolites as defense strategies to avoid predation. Manzamine A is a sponge-derived β-carboline-fused pentacyclic alkaloid with various bioactivities, including recently reported anticancer activity on pancreatic cancer. However, its cytotoxicity and mode of action against other tumors remain unclear. In this study, we exhibit that Manzamine A reduced cell proliferation in several colorectal cancer (CRC) cell lines. To further investigate the Manzamine A triggered molecular regulation, we analyzed the gene expression with microarray and revealed that pathways including cell cycle, DNA repair, mRNA metabolism, and apoptosis were dysregulated. We verified that Manzamine A induced cell cycle arrest at G₀/G₁ phase via inhibition of cyclin-dependent kinases by p53/p21/p27 and triggered a caspase-dependent apoptotic cell death through mitochondrial membrane potential depletion. Additionally, we performed bioinformatics analysis and demonstrated that Manzamine A abolished epithelial⁻mesenchymal transition process. Several mesenchymal transcriptional factors, such as Snail, Slug, and Twist were suppressed and epithelial marker E-cadherin was induced simultaneously in HCT116 cells by Manzamine A, leading to the epithelial-like phenotype and suppression of migration. These findings suggest that Manzamine A may serve as a starting point for the development of an anticancer drug for the treatment of metastatic CRC.
Manzamine A, a marine-derived alkaloid, inhibits accumulation of cholesterol ester in macrophages and suppresses hyperlipidemia and atherosclerosis in vivo
Bioorg Med Chem 2013 Jul 1;21(13):3831-8.PMID:23665143DOI:10.1016/j.bmc.2013.04.025.
The formation of foam cells in macrophages plays an essential role in the progression of early atherosclerotic lesions and therefore its prevention is considered to be a promising target for the treatment of atherosclerosis. We found that an extract of the marine sponge Acanthostrongylophora ingens inhibited the foam cell formation induced by acetylated low-density lipoprotein (AcLDL) in human monocyte-derived macrophages, as measured based on the accumulation of cholesterol ester (CE). Bioassay-guided purification of inhibitors from the extract afforded manzamines. Manzamine A was the most potent inhibitor of foam cell formation, and also suppressed CE formation in Chinese hamster ovary cells overexpressing acyl-CoA:cholesterol acyl-transferase (ACAT)-1 or ACAT-2. In addition, Manzamine A inhibited ACAT activity. Next, we orally administered Manzamine A to apolipoprotein E (apoE)-deficient mice for 80 days, and found that total cholesterol, free cholesterol, LDL-cholesterol, and triglyceride levels in serum were significantly reduced and the area of atherosclerotic lesions in the aortic sinus was also substantially diminished. These findings clearly suggest that Manzamine A suppresses hyperlipidemia and atherosclerosis in apoE-deficient mice by inhibiting ACAT and is therefore a promising lead compound in the prevention or treatment of atherosclerosis. Although Manzamine A has been reported to show several biological activities, this is the first report of a suppressive effect of Manzamine A on atherosclerosis in vivo.
RIP1 Mediates Manzamine-A-Induced Secretory Autophagy in Breast Cancer
Mar Drugs 2023 Feb 25;21(3):151.PMID:36976201DOI:10.3390/md21030151.
Cancer-derived small extracellular vesicles (sEVs) serve as critical mediators of cell-to-cell communication. Manzamine A (MA), a unique marine-derived alkaloid with various bioactivities, exerts anticancer effects against several kinds of tumors, but it remains unclear whether it has the same activity against breast cancer. Here, we proved that MA inhibits MDA-MB-231 and MCF-7 cell proliferation, migration, and invasion in a time- and dose-dependent manner. In addition, MA promotes autophagosome formation but suppresses autophagosome degradation in breast cancer cells. Importantly, we also found that MA stimulates sEVs secretion and increases autophagy-related protein accumulation in secreted sEVs, further potentiated by autophagy inhibitor chloroquine (CQ). Mechanistically, MA decreases the expression level of RIP1, the key upstream regulator of the autophagic pathway, and reduces the acidity of lysosome. Overexpression of RIP1 activated AKT/mTOR signaling, thus attenuating MA-induced autophagy and the corresponding secretion of autophagy-associated sEVs. Collectively, these data suggested that MA is a potential inhibitor of autophagy by preventing autophagosome turnover, and RIP1 mediates MA-induced secretory autophagy, which may be efficacious for breast cancer treatment.
Manzamine A as a novel inhibitor of herpes simplex virus type-1 replication in cultured corneal cells
Planta Med 2011 Jan;77(1):46-51.PMID:20645244DOI:10.1055/s-0030-1250093.
This study investigated the putative inhibitory effect of Manzamine A on HSV-1 infection. Our results indicated that Manzamine A effectively inhibited viral replication and infection in the cell line SIRC, a corneal cell line, at 1 µM. The existing anti-HSV-1 drug acyclovir was analyzed and showed a comparable activity at 50 µM. Plaque assays demonstrated that Manzamine A reduced the release of infectious virus by 10 (11)-fold. RTPCR assays indicated that HSV-1 virion host shutoff (vhs) activity and ICP0 transcription were decreased by Manzamine A treatment. These results bode well for the development of manzamines as potential leads to reduce viral infection in corneal cells and to prevent HSV-1-induced eye infections such as keratitis.