Cyclopiazonic acid
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| Category | Mycotoxins |
| Catalog number | BBF-01748 |
| CAS | 18172-33-3 |
| Molecular Weight | 336.39 |
| Molecular Formula | C20H20N2O3 |
| Purity | 98% (HPLC) |
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Description
It is produced by the strain of Various penicillium. It's a mycotoxin and it's neurotoxic. Its toxicity is linked to its ability to specifically and reversibly inhibit sarco-endoplasmic reticulum Ca2+-ATPases.
Specification
| Synonyms | (6aR,11aS,11bR)-10-Acetyl-11-hydroxy-7,7-dimethyl-2,6,6a,7,11a,11b-hexahydro-9H-pyrrolo[1',2':2,3]isoindolo[4,5,6-cd]indol-9-one |
| Storage | -20 °C |
| IUPAC Name | (2R,3S,9R)-5-acetyl-6-hydroxy-8,8-dimethyl-7,16-diazapentacyclo[9.6.1.02,9.03,7.015,18]octadeca-1(17),5,11(18),12,14-pentaen-4-one |
| Canonical SMILES | CC(=O)C1=C(N2C(C1=O)C3C(C2(C)C)CC4=C5C3=CNC5=CC=C4)O |
| InChI | InChI=1S/C20H20N2O3/c1-9(23)14-18(24)17-16-11-8-21-13-6-4-5-10(15(11)13)7-12(16)20(2,3)22(17)19(14)25/h4-6,8,12,16-17,21,25H,7H2,1-3H3/t12-,16+,17+/m1/s1 |
| InChI Key | RLOAZVAJNNPPDI-DQYPLSBCSA-N |
| Source | Cyclopiazonic acid (CPA) is a myxotoxin originally isolated from Penicillium cyclopium and subsequently from Penicillium griseofulvum, Penicillium camembertii, Aspergillus flavus and Aspergillus versicolor. It is often found co-occurring with aflatoxins. |
Properties
| Appearance | White Solid |
| Boiling Point | 598.6 °C at 760 mmHg |
| Melting Point | 245-246 °C |
| Density | 1.42 g/cm3 |
| Solubility | Soluble in chloroform, DMSO |
Toxicity
| Carcinogenicity | No indication of carcinogenicity to humans (not listed by IARC). |
| Lethal Dose | LD50: 13 mg/kg (Intraperitoneal, Mouse); LD50: 2.3 mg/kg (Intraperitoneal, Rat). |
| Mechanism Of Toxicity | Cyclopiazonic acid is potent and specific inhibitor of the endoplasmic and sarcoplasmic reticulum Ca+-dependent ATPases, which are essential for calcium reuptake in the muscle contraction-relaxation cycle. CPA blocks the calcium access channel and rigidifies a subset of transmembrane helices in a nonnative configuration that is incompatible with calcium binding. Inhibition of Ca2+-ATPases results in cell death through the activation of stress-response and apoptotic pathways within the endoplasmic reticulum and mitochondria. CPA can also induce both secretion and mRNA levels of proinflammatory cytokines, likely leading to macrophage activation and immunotoxic effects. In addition, it has been shown to be mutagenic and genotoxic. Mycotoxins are often able to enter the liver and kidney by human organic anion transporters (hOATs) and human organic cation transporters (hOCTs). They can also inhibit uptake of anions and cations by these transporters, interefering with the secretion of endogenous metabolites, drugs, and xenobiotics including themselves. This results in increased cellular accumulation of toxic compounds causing nephro- and hepatotoxicity. |
Reference Reading
1. Inhibitory Effects of Cyclopiazonic Acid on the Pacemaker Current in Sinoatrial Nodal Cells
Hong-Lin Wu, Ying Dong, Qian Chen, Xiao-Ting Xie, Guo-Jian Xiang, Mei-Yan Chen, Yang Li, Jian-Cheng Zhang, Jian-Quan Chen, Peng-Li Zhu Neuroscience . 2020 May 1;433:230-240. doi: 10.1016/j.neuroscience.2020.01.018.
Objective:The spontaneous action potential of isolated sinoatrial node (SAN) cells is regulated by a coupled-clock system of two clocks: the calcium clock and membrane clock. However, it remains unclear whether calcium clock inhibitors have a direct effect on the membrane clock. The purpose of this study was to investigate the direct effect of cyclopiazonic acid (CPA), a selective calcium clock inhibitor, on the function of the membrane clock of SAN cells.Methods:at SAN cells were isolated by trypsinization and identified based on morphology and electrophysiology. Ifand HCN currents were recorded via patch clamp technique. The expression of the HCN channel protein was determined by Western blotting analysis.Results:The diastolic depolarization rate of spontaneous action potentials and the current densities of Ifwere reduced by exposure to 10 μM CPA. The inhibitory effect of CPA was concentration-dependent with an IC50value of 16.3 μM and a Hill coefficient of 0.98. The effect of CPA on Ifcurrent was also time-dependent, and the Ifcurrent amplitude was partially restored after washout. Furthermore, the steady-state activation curve of the Ifcurrent was shifted to a negative potential, indicating that channel activation slowed down. Finally, the protein expression of HCN4 in HEK293 cells was markedly downregulated by CPA.Conclusions:These results indicate that the direct inhibition effect of CPA on the Ifcurrent in SAN cells is both concentration- and time-dependent. The underlying mechanisms may involve slowing down steady-state activation and the downregulation of pacemaker channel protein expression.
2. Detection of cyclopiazonic acid (CPA) in maize by immunoassay
C M Maragos, J Bobell, K K Sieve Mycotoxin Res . 2017 May;33(2):157-165. doi: 10.1007/s12550-017-0275-0.
Cyclopiazonic acid (α-CPA) is a tremorgenic mycotoxin that is commonly produced by certain species of the aspergilli, in particular Aspergillus flavus, which is more widely known for production of the aflatoxins. Despite the fact that α-CPA may co-occur with aflatoxins, immunoassay-based methods for monitoring for CPA have not been widely developed. We report the development and evaluation of several monoclonal antibodies (mAbs) for α-CPA. Two mAbs in particular were very sensitive, with IC50s of 1.1 and 1 ng/mL (clones 1418 and 1231, respectively). Tolerances to aqueous methanol or acetonitrile were good, which permitted the development of an antigen-immobilized competitive enzyme-linked immunosorbent assay (CI-ELISA) for detection of CPA in maize. Spiked or naturally contaminated maize, extracted with aqueous methanol, was diluted with buffer for analysis. The working range for the assay (IC20to IC80) was from 5 to 28 μg/kg. Recoveries from maize spiked over the range from 2 to 50 μg/kg averaged 88.6 ± 12.6%. Twenty-eight samples of maize were tested by both the CI-ELISA and a liquid chromatography-fluorescence (LC-FLD) method. For the five samples above the limits of quantitation of both methods, CI-ELISA tended to overestimate CPA content, a difference that we speculate may be due to related metabolites or perhaps "masked" derivatives of CPA. The antibodies developed and the resulting CI-ELISA will be useful tools for further evaluation of the prevalence of this mycotoxin in maize.
3. Cyclopiazonic Acid and Okaramine Analogues, Including Chlorinated Compounds, from Chrysosporium undulatum YT-1
Lingyan Liu, Zhangyi Qin, Tao Yang, Xueqing Qian, Bo Ren, Guoyou Li, Dongmei Fang J Nat Prod . 2022 Nov 25;85(11):2547-2556. doi: 10.1021/acs.jnatprod.2c00445.
Eight new cyclopiazonic acid (1-8) and five new okaramine (9-13) alkaloids together with 13 known compounds were isolated from the fungusChrysosporium undulatumYT-1. Compounds2,4,5,7,10,11, and13were chlorinated indole alkaloids. The structures of compounds1-13were elucidated by HRESIMS and NMR spectroscopic data. Their relative and absolute configurations were established byJ-based configuration analysis, NOESY, NOEDIFF experiments, ECD spectroscopic data, and biogenetic considerations. Compound4inhibited the growth ofBacillus subtiliswith an MIC value of 6.3 μg/mL. Compounds9-11exhibited strong insecticidal capacity against the third instar larvae of silkworm and cotton bollworm (LD50: ≤7.56 μg/g). At 40 μM, compound1showed obvious neuroprotection to the PC12 cells with 6-OHDA treatment.
Spectrum
Predicted LC-MS/MS Spectrum - 10V, Positive
Experimental Conditions
Ionization Mode: Positive
Collision Energy: 10 eV
Instrument Type: QTOF (generic), spectrum predicted by CFM-ID
Mass Resolution: 0.0001 Da
Molecular Formula: C20H20N2O3
Molecular Weight (Monoisotopic Mass): 336.1474 Da
Molecular Weight (Avergae Mass): 336.3844 Da
Collision Energy: 10 eV
Instrument Type: QTOF (generic), spectrum predicted by CFM-ID
Mass Resolution: 0.0001 Da
Molecular Formula: C20H20N2O3
Molecular Weight (Monoisotopic Mass): 336.1474 Da
Molecular Weight (Avergae Mass): 336.3844 Da
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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 ╳
