Asperphenamate
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| Category | Enzyme inhibitors |
| Catalog number | BBF-04493 |
| CAS | 63631-36-7 |
| Molecular Weight | 506.59 |
| Molecular Formula | C32H30N2O4 |
| Purity | ≥95% |
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Description
Asperphenamate is a fungal secondary metabolite isolated from Aspergillus flavipes. Asperphenamate has been found in a broad range of Pencillium and Aspergillus species and even in plants, as a product of endophytic fungi. Asperphenamate has weak antitumor activity. 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). Asperphenamate is also used to synthesize N-Benzoyl-O-(N'-(1-benzyloxycarbonyl-4-piperidiylcarbonyl)-D-phenylalanyl)-D-phenylalaninol (BBP), an asperphenamate derivative that inhibits human breast carcinoma MCF-7 cell growth.
Specification
| Synonyms | (S)-N-Benzoyl-L-phenylalanine 2-(Benzoylamino)-3-phenylpropyl Ester; N-Benzoyl-phenylalanine 2-benzoylamino-3-phenylpropyl Ester; N-Benzoyl-L-phenylalaninol N-benzoyl-L-phenylalaninate; Anabellamide; Asjanin; NSC 306231; Auranamide |
| Storage | Store at -20°C |
| IUPAC Name | [(2S)-2-benzamido-3-phenylpropyl] (2S)-2-benzamido-3-phenylpropanoate |
| Canonical SMILES | C1=CC=C(C=C1)CC(COC(=O)C(CC2=CC=CC=C2)NC(=O)C3=CC=CC=C3)NC(=O)C4=CC=CC=C4 |
| InChI | InChI=1S/C32H30N2O4/c35-30(26-17-9-3-10-18-26)33-28(21-24-13-5-1-6-14-24)23-38-32(37)29(22-25-15-7-2-8-16-25)34-31(36)27-19-11-4-12-20-27/h1-20,28-29H,21-23H2,(H,33,35)(H,34,36)/t28-,29-/m0/s1 |
| InChI Key | CVULDJMCSSACEO-VMPREFPWSA-N |
Properties
| Appearance | Solid Powder |
| Antibiotic Activity Spectrum | Neoplastics (Tumor); Yeast |
| Boiling Point | 774.3°C at 760 mmHg |
| Density | 1.198 g/cm3 |
| Solubility | Soluble in Ethanol, Methanol, DMSO |
Reference Reading
1. Discovery of novel cathepsin inhibitors with potent anti-metastatic effects in breast cancer cells
Yang Liu, Chunyang Zou, Jian Wang, Enlong Ma, Baichun Hu, Jun Liu, Wentao Ge, Wenhui He, Lei Yuan, Lei Sheng Bioorg Chem . 2018 Dec;81:672-680. doi: 10.1016/j.bioorg.2018.09.029.
It is still challenging to determine the potential targets of natural products, which is essential for further drug research and development. Due to its novel mechanism of action of inducing autophagy effects in breast cancer cells, asperphenamate has received our considerable attention. However, its unknown target inevitably impedes further study. In our previous work, the target enzyme of asperphenamate was predicted as cathepsin by the natural product consensus pharmacophore strategy. Then, asperphenamate and its three derivatives were chosen to study in detail by molecular docking calculations with AutoDock 4 suite. The docking results showed the three derivatives interacted more tightly with either cathepsin L or cathepsin S than with asperphenamate. The ortho-benzyloxyl phenylacetyl derivative 1 andp-toluenesulfonyl derivative 3 showed similar interactions with cathepsin L and adopted a better geometric shape within the binding pocket than did the N-CBZ-piperidyl analog 2. On the other hand, compound 2 formed more hydrogen bonds than 1 and 3 to make it tightly bind within cathepsin S. The cathepsin inhibitory activity assay verified the molecular simulation results. Compound 2 was remarkably less active than 1 and 3 against cathepsin L. However, compound 2 showed the strongest potency against cathepsin S with IC50of 13.12 ± 0.29 μM. Considering that cathepsin S plays a vital role in the process of metastasis in breast cancer cells, the inhibitory effect of 2 on migration and invasion was further studied in human breast cancer MDA-MB-231 cells by wound healing and transwell chamber assays. The results illustrated that 2 exhibited an apparent inhibitory ability to the metastasis of MDA-MB-231 cells. Next, 2 will be chosen as a lead compound to develop novel double functional chemotherapeutic agents with both novel mechanisms of action against apoptosis-resistant cancer cells, such as inducing autophagy and inhibiting cancer metastasis.
2. Asperphenamate biosynthesis reveals a novel two-module NRPS system to synthesize amino acid esters in fungi
Aili Fan, Peng Zhang, Wen-Bing Yin, Zhiqiang An, Long Wang, Wei Li, Zhiguo Liu Chem Sci . 2018 Jan 24;9(9):2589-2594. doi: 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 inPenicillium brevicompactumand heterologous expression inAspergillus 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.
3. JNK-dependent Atg4 upregulation mediates asperphenamate derivative BBP-induced autophagy in MCF-7 cells
Enlong Ma, Xiaoshuo Mu, Caixia Miao, Yanchun Li, Jianchun Li, Wei Xiao, Tiemin Sun, Qiyu Luo, Lei Yuan Toxicol Appl Pharmacol . 2012 Aug 15;263(1):21-31. doi: 10.1016/j.taap.2012.05.018.
N-Benzoyl-O-(N'-(1-benzyloxycarbonyl-4-piperidiylcarbonyl)-D-phenylalanyl)-D-phenylalaninol (BBP), a novel synthesized asperphenamate derivative with the increased solubility, showed growth inhibitory effect on human breast carcinoma MCF-7 cells in a time- and concentration-dependent manner. The growth inhibitory effect of BBP was associated with induction of autophagy, which was demonstrated by the development of acidic vesicular organelles, cleavage of LC3 and upregulation of Atg4 in BBP-treated MCF-7 cells. Since the application of Atg4 siRNA totally blocked the cleavage of LC3, we demonstrated a central role of Atg4 in BBP-induced autophagy. The further studies showed that BBP increased the levels of reactive oxygen species (ROS), and pretreatment with NAC effectively blocked the accumulation of ROS, autophagy and growth inhibition triggered by BBP. Moreover, BBP induced the activation of JNK, and JNK inhibitor SP600125 reversed autophagy, the increase of Atg4 levels, conversion of LC3 and growth inhibition induced by BBP. Knockdown of JNK by siRNA efficiently inhibited ROS production and autophagy, but antioxidant NAC failed to block JNK activation induced by BBP, indicating that JNK activation may be a upstream signaling of ROS and should be a core component in BBP-induced autophagic signaling pathway. These results suggest that BBP produces its growth inhibitory effect through induction of the autophagic cell death in MCF-7 cells, which is modulated by a JNK-dependent Atg4 upregulation involving ROS production.
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Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
