Penicillic acid has antimicrobial and cytotoxic properties. It inhibits bacterial quorum sensing communication at 80 μM. It also exhibits mutagenic and carcinogenic potential. As a mycotoxin, it is a toxic secondary metabolite that can cause health problems in animals and humans upon exposure.

In vitro, Penicillic acid demonstrates antimicrobial and cytotoxic activities. It inhibits bacterial growth. It has been shown to inhibit bacterial quorum sensing communication. Its cytotoxic effects are likely due to its ability to inhibit DNA synthesis and cause DNA damage.

In vivo, Penicillic acid is a mycotoxin that can cause toxicity in animals. Long-term ingestion of feed containing penicillic acid can cause liver enlargement, liver cell degeneration, and inhibition of DNA synthesis in animal cells. In severe cases, it can cause DNA breakage. It is a hazard in the livestock industry.

The in vitro antimicrobial assay for Penicillic acid involves testing its activity against bacterial or fungal cultures. The compound is serially diluted in a liquid growth medium, and a standardized inoculum of the microorganism is added. After incubation, the minimum inhibitory concentration (MIC) is determined. Its ability to inhibit quorum sensing can be assessed using a reporter strain.

In vitro cell culture studies for Penicillic acid are performed in mammalian cell lines to assess its cytotoxicity. Cells are treated with varying concentrations of the compound, and cell viability is assessed using an MTT or SRB assay. Its ability to induce DNA damage can be assessed by the comet assay or by measuring the phosphorylation of H2AX.

In vivo animal experiments for Penicillic acid are often performed to study its toxic effects. Animals are administered the compound orally, and parameters such as liver function (ALT, AST), body weight, and histopathology of organs (especially the liver) are assessed. Its carcinogenic potential can be studied in long-term bioassays.

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)
Penicillic acid has a molecular formula of C8H10O4 and a molecular weight of 170.16 g/mol. It is a white to light beige crystalline powder. It is soluble in organic solvents. It is typically stored as a powder at -20°C for long-term stability. Its stability is maintained under recommended storage conditions.

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)

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Toxicity Data
LD50: 600 mg/kg (oral, mouse) (A3013)
LD50: 250 mg/kg (intravenous, mouse) (A3013)
LD50: 90 mg/kg (intraperitoneal, mouse) (A3013)

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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.
Toxicological data for Penicillic acid indicate that it is a mycotoxin with significant toxicity. It is mutagenic and carcinogenic. It can cause liver damage and inhibit DNA synthesis. It is a hazard in food and feed and is not intended for human consumption.

[1]. Toxicity of penicillic acid for rat alveolar macrophages in vitro. Environ Res. 1986 Dec;41(2):505-13.

[2]. The mycotoxin penicillic acid inhibits Fas ligand-induced apoptosis by blocking self-processing of caspase-8 in death-inducing signaling complex. J Biol Chem. 2003 Feb 21;278(8):5786-93.

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.
Penicillic acid is a research compound with no clinical approval. It is used as a mycotoxin standard in analytical chemistry and food safety testing. It is also used to study the mechanisms of mycotoxin toxicity and to develop methods for detecting and mitigating mycotoxin contamination in food and feed.

C8H10O4

170.16300

170.057

C, 56.47; H, 5.92; O, 37.61

90-65-3

90-65-3

5385314

White to off-white solid powder

1.2±0.1 g/cm3

285.7±35.0 °C at 760 mmHg

83-87ºC

113.5±19.4 °C

0.0±1.3 mmHg at 25°C

1.482

0.84

1

4

4

12

250

0

O=C(C=C(C(C(C)=C)=O)OC)O

VOUGEZYPVGAPBB-XQRVVYSFSA-N

InChI=1S/C8H10O4/c1-5(2)8(11)6(12-3)4-7(9)10/h4H,1H2,2-3H3,(H,9,10)/b6-4-

(2Z)-3-methoxy-5-methyl-4-oxohexa-2,5-dienoic acid

Penicillic acid

2934.99.9001

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.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: ~100 mg/mL (~587.7 mM)
H2O: ~25 mg/mL (~146.9 mM)

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.

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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.

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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.
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 corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)