Asperphenamate
(Synonyms: Anabellamide, Auranamide, NSC 306231) 目录号 : GC40769
A fungal secondary metabolite
Cas No.:63631-36-7
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
Asperphenamate is a fungal secondary metabolite originally isolated from A. flavipes. It inhibits proliferation of T47D and MDA-MB-231 breast and HL-60 leukemia cancer cell lines (IC50s = 92.3, 96.5, and 97.9 μM, respectively) and inhibits yeast α-glucosidase activity (IC50 = 8.3 μM).
| Cas No. | 63631-36-7 | SDF | |
| 别名 | Anabellamide, Auranamide, NSC 306231 | ||
| Canonical SMILES | O=C(N[C@@H](CC1=CC=CC=C1)COC([C@H](CC2=CC=CC=C2)NC(C3=CC=CC=C3)=O)=O)C4=CC=CC=C4 | ||
| 分子式 | C32H30N2O4 | 分子量 | 506.6 |
| 溶解度 | DMF: soluble,DMSO: soluble,Ethanol: soluble,Methanol: soluble | 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 | 1.9739 mL | 9.8697 mL | 19.7394 mL |
| 5 mM | 0.3948 mL | 1.9739 mL | 3.9479 mL |
| 10 mM | 0.1974 mL | 0.987 mL | 1.9739 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。
Asperphenamate biosynthesis reveals a novel two-module NRPS system to synthesize amino acid esters in fungi
Chem Sci 2018 Jan 24;9(9):2589-2594.PMID:29719714DOI:10.1039/c7sc02396k.
Amino acid esters are a group of structurally diverse natural products with distinct activities. Some are synthesized through an inter-molecular esterification step catalysed by nonribosomal peptide synthetase (NRPS). In bacteria, the formation of the intra-molecular ester bond is usually catalysed by a thioesterase domain of NRPS. However, the mechanism by which fungal NRPSs perform this process remains unclear. Herein, by targeted gene disruption in Penicillium brevicompactum and heterologous expression in Aspergillus nidulans, we show that two NRPSs, ApmA and ApmB, are sufficient for the synthesis of an amino acid ester, Asperphenamate. Using the heterologous expression system, we identified that ApmA, with a reductase domain, rarely generates dipeptidyl alcohol. In contrast, ApmB was determined to not only catalyse inter-molecular ester bond formation but also accept the linear dipeptidyl precursor into the NRPS chain. The mechanism described here provides an approach for the synthesis of new small molecules with NRPS as the catalyst. Our study reveals for the first time a two-module NRPS system for the formation of amino acid esters in nature.
Mass Spectrometry Guided Discovery and Design of Novel Asperphenamate Analogs From Penicillium astrolabium Reveals an Extraordinary NRPS Flexibility
Front Microbiol 2021 Jan 15;11:618730.PMID:33519780DOI:10.3389/fmicb.2020.618730.
Asperphenamate is a small peptide natural product that has gained much interest due to its antitumor activity. In the recent years numerous bioactive synthetic Asperphenamate analogs have been reported, whereas only a handful of natural analogs either of microbial or plant origin has been discovered. Herein we describe a UHPLC-HRMS/MS and amino acid supplement approach for discovery and design of novel Asperphenamate analogs. Chemical analysis of Penicillium astrolabium, a prolific producer of Asperphenamate, revealed three previously described and two novel Asperphenamate analogs produced in significant amounts, suggesting a potential for biosynthesis of further Asperphenamate analogs by varying the amino acid availability. Subsequent growth on proteogenic and non-proteogenic amino acid enriched media, revealed a series of novel Asperphenamate analogs, including single or double amino acid exchange, as well as benzoic acid exchange for nicotinic acid, with the latter observed from a natural source for the first time. In total, 22 new Asperphenamate analogs were characterized by HRMS/MS, with one additionally confirmed by isolation and NMR structure elucidation. This study indicates an extraordinary nonribosomal peptide synthetase (NRPS) flexibility based on substrate availability, and therefore the potential for manipulating and designing novel peptide natural products in filamentous fungi.
Rapid detection of Asperphenamate in a hay batch associated with constipation and deaths in dairy cattle. The application of DART-HRMS to veterinary forensic toxicology
Toxicon 2020 Nov;187:122-128.PMID:32891666DOI:10.1016/j.toxicon.2020.08.022.
Direct analysis in real time (DART) coupled to high-resolution mass spectrometry (HRMS) was applied for the first time to veterinary forensic toxicology to investigate the presence of toxic compounds in hay after an episode of acute intoxication in a dairy cattle farm. In addition to gross field necropsy and histological examination, microbial cultures, and heavy metals analysis, the molecular fingerprinting of the suspected hay batch was investigated by DART-HRMS. DART-HRMS revealed a distinct signal of m/z 507.2289 in the hay batch thought to be associated with the digestive complications. A search on chemical structure databases matched the ion with Asperphenamate, a toxin produced by Penicillium spp. and Aspergillus spp. Liquid Chromatography-HMRS analysis and electrospray-HRMS-MS/MS of the hay extracts further characterized the structure and confirmed the identification of the compound as Asperphenamate. Asperphenamate is fungal metabolite which can have cytotoxic and antitumor activity in humans, and it is classified as acute toxicant and harmful if swallowed.
Design, synthesis and biological evaluation of novel Asperphenamate derivatives
Eur J Med Chem 2016 Mar 3;110:76-86.PMID:26807546DOI:10.1016/j.ejmech.2016.01.020.
A series of novel Asperphenamate derivatives were designed and synthesized, including series I (the A-phenyl group replaced with various aromatic heterocycles) and series II (the acyl group substituted by sulfonyl group). All compounds have been screened for their antiproliferative activity in vitro against MCF-7, HeLa, and BEL-7402 cell lines by the standard MTT method. Structure-activity relationship studies displayed the heterocycle type played an important role in activity. Six-membered ring derivatives displayed more potency than five-membered ring and the sulfonyl group in A-ring region made an important contribution to activity. Among all derivatives, tosyl derivative 8c exhibited the greatest potency in three human cancer cell lines. Especially in MCF-7 cells, the cellular potency of 8c was approximately 3.0-fold more potent than that of cisplatin. Firstly, the mechanism of cell death induced by 8c in MCF-7 cells was investigated. The results showed that the cell death was induced by autophagy instead of apoptosis or cell cycle arrest. Further studies indicated that 8c might induce autophagic cell death in HeLa and BEL-7402 cell lines.
Synthesis and in vitro antitumor activity of Asperphenamate derivatives as autophagy inducer
Bioorg Med Chem Lett 2012 Mar 15;22(6):2216-20.PMID:22361137DOI:10.1016/j.bmcl.2012.01.101.
In an effort to improve the aqueous solubility and the antitumor activity of natural product Asperphenamate, we have designed and synthesized three series of Asperphenamate derivatives, including series I (simplifying molecular skeleton series), series II (introducing a hydroxyl group to A-phenyl ring series) and series III (disrupting molecular planarity series). All derivatives have displayed a significantly increased solubility compared with Asperphenamate. Their growth inhibitory activities in vitro were screened by the standard MTT method in MCF-7, HeLa, and BEL-7402 cell lines. With the exception of the derivatives in series I, most of derivatives in series II and series III showed growth inhibitory activity. Among all derivatives, IM23b in series III showed the greatest potency in human breast cancer MCF-7 cells. The cellular potency of IM23b was approximately 1.5-fold more potent than that of cisplatin. The mechanism of cell death induced by IM23b in human breast cancer MCF-7 cells was further investigated. We concluded that the cell death was induced by autophagy instead of apoptosis or cell cycle arrest.