| Size | Price | Stock | Qty |
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| 5mg |
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Penicillic acid is a novel and potent polyketide mycotoxin with antibiotic and carcinogenic activity was isolated from various Aspergillus and Penicillium species. In vitro tests on rat alveolar macrophages (AM) reveal cytotoxicity. Penicillic acid prevents caspase-8 from processing itself, thereby inhibiting the apoptosis brought on by Fas ligands.
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
In vivo and in vitro studies have shown significant uptake of (14)C-penicillic acid by erythrocytes, with radioactivity in membrane components increasing significantly over time (1–4 hours). However, most hematologic activity occurs intracellularly. The concentration of 14C radioactivity in liver components accounts for 1.5% of that in RNA-DNA and protein components. The levels of 14C activity associated with these components increase over time (24 hours). Studies of 14C-labeled penicillic acid metabolism in rats have shown that a large amount of radioactive material is excreted in urine (82% of the administered dose after 7 days). Bile metabolites account for 10% of the administered dose 2 hours after administration. Metabolism/Metabolites Penicillic acid is a known metabolite associated with the blue cheese-producing strain Penicillium rochfeedilum. Of the penicillic acid metabolites detected in male mice, 10% were glucuronide conjugates. All metabolites in urine, plasma, and bile are more polar than the parent compound. The major metabolites are conjugates or derivatives of glutathione or cysteine. In the subcellular fractions of mouse liver homogenate, penicillic acid undergoes both enzymatic and non-enzymatic reactions with glutathione; both reactions are equally important. Metabolism of various subcellular fractions of the liver: In the absence of glutathione, this fraction undergoes virtually no enzymatic reaction; however, metabolic activity is enhanced in the presence of glutathione. In the presence of glutathione, 75% of added penicillic acid is bioconverted within 30 minutes into a more polar metabolite that cannot be extracted with organic solvents. Penicillic acid is rapidly absorbed and extensively metabolized in the liver. Its detoxification is achieved through interaction with glutathione S-transferase, and the metabolites are primarily excreted in the urine. (A3011, A3013) |
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| Toxicity/Toxicokinetics |
Toxicity Summary
Penicillic acid has been shown to inhibit alcohol dehydrogenases and lactate dehydrogenases by forming covalent adducts with cysteine or lysine residues at the enzyme's active site. Penicillic acid can also directly bind to the cysteine residue at the active site of the caspase-8 large subunit, thereby inhibiting FasL-induced apoptosis by targeting caspase-8 self-processing. Penicillic acid is also mutagenic, causing DNA single-strand breaks, chromosomal aberrations, and DNA synthesis inhibition. Mycotoxins typically enter the liver and kidneys via human organic anion transporters (hOATs) and human organic cation transporters (hOCTs). They can also inhibit the uptake of anions and cations by these transporters, thereby interfering with the secretion of endogenous metabolites, drugs, and exogenous substances (including themselves). This leads to an increased accumulation of toxic compounds within cells, resulting in nephrotoxicity and hepatotoxicity. (A2957, A3007, A3008, A3010, A3012, A3014) Toxicity Data LD50: 600 mg/kg (oral, mouse) (A3013) LD50: 250 mg/kg (intravenous, mouse) (A3013) LD50: 90 mg/kg (intraperitoneal, mouse) (A3013) Interactions Penicillic acid and ochratoxin A are synergistic toxic fungal metabolites. In vitro, penicillic acid reduces the conversion of parent ochratoxin A to the non-toxic metabolite α-ochratoxin. In vivo, repeated oral administration of penicillic acid inhibits pancreatic carboxypeptidase A activity in mice and chickens. The toxic interaction pattern of the two mycotoxins may be due to impaired ochratoxin A detoxification caused by penicillic acid depletion of carboxypeptidase A activity. Pretreatment with pentobarbital and 3-methylcholanthrene increased acute cytotoxicity of penicillic acid in mice, while SKF-525A reduced its toxicity. Administration of cysteine 5 minutes before, rather than 20 minutes after, penicillic acid administration protected mice from toxicity, while pretreatment with diethyl maleate increased penicillic acid toxicity in mice. |
| References | |
| Additional Infomation |
3-Methoxy-5-methyl-4-oxo-2,5-hexadienoic acid has been reported and data are available. Penicillic acid is a mycotoxin produced by various Aspergillus and Penicillium fungi. It has antibacterial activity, but also exhibits cytotoxicity, hepatotoxicity, and carcinogenicity. Penicillic acid poses a threat to human health because it is present in contaminated crops (e.g., corn). (A2957, A3013) Penicillic acid is a mycotoxin with antibacterial and carcinogenic activities produced by various Penicillium and Aspergillus strains. It is found in tobacco, sausage, and corn. Mechanism of Action: Its carcinogenic activity is attributed to α,β-unsaturated bonds and an external conjugated double bond attached to the 4-position of the γ-lactone ring… The effects of penicillic acid on isolated frog hearts and Na⁺, K⁺, and Ca²⁺ ions have been studied. Studies have found that penicillic acid can inhibit these ions from entering myocardial tissue, leading to cardiac arrest. This blockage can be cleared by perfusion with Ringer's solution.
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| Molecular Formula |
C8H10O4
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|---|---|
| Molecular Weight |
170.16300
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| Exact Mass |
170.057
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| Elemental Analysis |
C, 56.47; H, 5.92; O, 37.61
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| CAS # |
90-65-3
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| Related CAS # |
90-65-3
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| PubChem CID |
5385314
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
285.7±35.0 °C at 760 mmHg
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| Melting Point |
83-87ºC
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| Flash Point |
113.5±19.4 °C
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| Vapour Pressure |
0.0±1.3 mmHg at 25°C
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| Index of Refraction |
1.482
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| LogP |
0.84
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
12
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| Complexity |
250
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C=C(C(C(C)=C)=O)OC)O
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| InChi Key |
VOUGEZYPVGAPBB-XQRVVYSFSA-N
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| InChi Code |
InChI=1S/C8H10O4/c1-5(2)8(11)6(12-3)4-7(9)10/h4H,1H2,2-3H3,(H,9,10)/b6-4-
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| Chemical Name |
(2Z)-3-methoxy-5-methyl-4-oxohexa-2,5-dienoic acid
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| Synonyms |
Penicillic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~100 mg/mL (~587.7 mM)
H2O: ~25 mg/mL (~146.9 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (14.69 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (14.69 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (14.69 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 5.8768 mL | 29.3841 mL | 58.7682 mL | |
| 5 mM | 1.1754 mL | 5.8768 mL | 11.7536 mL | |
| 10 mM | 0.5877 mL | 2.9384 mL | 5.8768 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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