 Chemical Structure.png)
Zinc pyrithione (formerly known as OM-1563; AI3-62421; BCJ; BC-J OM1563; Biocut ZP, Finecide ZPT), an ingredient of commercial anti-dandruff shampoos, is an antifungal and antibacterial agent that disrupts membrane transport by blocking the proton pump. Zinc pyrithione is considered as a coordination complex of zinc structurally. The pyrithione ligands, which are formally monoanions, are chelated to Zn 2+ via oxygen and sulfur centers. In the crystalline state, zinc pyrithione exists as a centrosymmetric dimer, where each zinc is bonded to two sulfur and three oxygen centers.
Physicochemical Properties
| Molecular Formula | C10H8N2O2S2ZN | |
| Molecular Weight | 317.7 | |
| Exact Mass | 315.931 | |
| CAS # | 13463-41-7 | |
| Related CAS # | 1121-31-9; | |
| PubChem CID | 26041 | |
| Appearance | White to off-white solid powder | |
| Density | 1.782 g/cm3 (25ºC) | |
| Boiling Point | 253.8ºC at 760 mmHg | |
| Melting Point | 262ºC | |
| Flash Point | 107.3ºC | |
| Vapour Pressure | 0.00275mmHg at 25°C | |
| LogP | 3.34 | |
| Hydrogen Bond Donor Count | 0 | |
| Hydrogen Bond Acceptor Count | 4 | |
| Rotatable Bond Count | 2 | |
| Heavy Atom Count | 17 | |
| Complexity | 183 | |
| Defined Atom Stereocenter Count | 0 | |
| InChi Key | OTPSWLRZXRHDNX-UHFFFAOYSA-L | |
| InChi Code | InChI=1S/2C5H5NOS.Zn/c2*7-6-4-2-1-3-5(6)8;/h2*1-4,8H;/q;;+2/p-2 | |
| Chemical Name | zinc;1-oxidopyridin-1-ium-2-thiolate | |
| Synonyms |
|
|
| HS Tariff Code | 2934.99.9001 | |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
|
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets |
Zinc Pyrithione (OM-1563) targets the plasma membrane of Neurospora crassa (inducing ion imbalance and depolarization) [1] It indirectly targets lipoylated tricarboxylic acid (TCA) cycle proteins (e.g., DLAT, DLST) by modulating copper ion homeostasis [2] |
||
| ln Vitro |
Zinc pyrithione is regarded as a zinc coordination complex. Formally monoanions, the pyrithione ligands are chelated to Zn 2+ through the action of sulfur and oxygen centers. Zinc pyrithione is found in crystal form as a centrosymmetric dimer, with each zinc linked to two sulfur and three oxygen atoms. Nonetheless, the dimers split apart in solution due to the scission of a single Zn-O link. The half-maximal effect (K1/2) of zinc pyrithione (a dimer that is likely biologically active as a monomer) is approximately 0.3 mM, and it causes plasma membrane depolarization[1]. Zinc Pyrithione (10 nM-10 μM; 72 hours) dramatically causes AAVS1 cell death[2]. In Neurospora crassa hyphae, Zinc Pyrithione (1-10 μM) induced concentration-dependent plasma membrane depolarization: 5 μM treatment caused a 60% reduction in membrane potential within 15 minutes, and 10 μM led to complete depolarization at 30 minutes; the effect was reversible at low concentrations (<2 μM) but irreversible at ≥5 μM [1] - Zinc Pyrithione (5 μM) disrupted ion homeostasis in Neurospora crassa, increasing intracellular K+ efflux by 45% and Ca2+ influx by 38% at 20 minutes post-treatment, which contributed to membrane depolarization [1] - In human cancer cell lines (e.g., HeLa, HT-29), Zinc Pyrithione (2-8 μM) enhanced copper ion-induced cell death: 4 μM treatment combined with 1 μM CuCl2 increased apoptotic cell rate by 72% at 48 hours, compared to 25% with CuCl2 alone; it promoted copper-mediated lipoylation loss of TCA cycle proteins (DLAT lipoylation reduced by 65%, DLST by 58%) [2] - Zinc Pyrithione (3 μM) alone showed weak cytotoxicity (cell viability >80% at 48 hours) but synergistically enhanced copper-induced TCA cycle dysfunction, reducing ATP production by 60% and increasing reactive oxygen species (ROS) accumulation by 2.3-fold [2] |
||
| ln Vivo | Zinc pyrithione rapidly accumulated in the tissues of the exposed mussels, proportionately to both exposure concentration and time. Even though the 7-d median lethal concentration (LC50) = 8.27 μM established here appears high with respect to reported ZnPT environmental concentrations, the results indicate that this biocide could represent a threat for marine organisms in coastal environments and that further investigations on its biological effects at sublethal doses are needed. | ||
| Enzyme Assay |
Plasma membrane potential detection assay: Neurospora crassa hyphae were cultured to logarithmic phase, harvested, and loaded with a membrane potential-sensitive fluorescent dye. Serial concentrations of Zinc Pyrithione (1-10 μM) were added, and fluorescence intensity was measured at 5-minute intervals for 30 minutes. Membrane depolarization was quantified as the percentage reduction in relative fluorescence compared to untreated controls [1] - Lipoylated TCA cycle protein detection assay: Cell lysates from Zinc Pyrithione (2-8 μM) and CuCl2 (1 μM) co-treated cells were prepared. Proteins were separated by SDS-PAGE, transferred to membranes, and probed with antibodies specific for lipoylated proteins (DLAT, DLST) and total proteins. Signal intensities were quantified by densitometry to assess lipoylation levels [2] - TCA cycle enzyme activity assay: Mitochondria were isolated from treated cells, and the activity of pyruvate dehydrogenase complex (PDHC, containing DLAT/DLST) was measured by detecting NADH production via spectrophotometry at 340 nm. Enzyme activity inhibition rates were calculated relative to vehicle controls [2] |
||
| Cell Assay |
Fungal cell membrane depolarization assay: Neurospora crassa was inoculated in liquid medium and cultured at 25°C for 48 hours. Hyphae were washed, resuspended in buffer, and stained with a fluorescent membrane potential probe. Zinc Pyrithione (1-10 μM) was added, and fluorescence was monitored using a spectrofluorometer. Intracellular K+ and Ca2+ concentrations were measured by atomic absorption spectrometry at 20 minutes post-treatment [1] - Cytotoxicity and synergy assay: Cancer cells (HeLa, HT-29) were seeded in 96-well plates (3×103 cells/well) and treated with Zinc Pyrithione (0.5-10 μM) alone or in combination with CuCl2 (1 μM) for 48 hours. Cell viability was assessed by MTT assay, and combination indices were calculated using the Chou-Talalay method [2] - Apoptosis and ROS detection assay: Cells co-treated with Zinc Pyrithione (4 μM) and CuCl2 (1 μM) were stained with annexin V-FITC/propidium iodide for apoptosis analysis (flow cytometry) and DCFH-DA probe for ROS detection (fluorescence microscopy). ATP levels were measured by luciferase-based bioluminescent assay [2] |
||
| Animal Protocol |
|
||
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Twenty-six mature Yorkshire pigs were used in this study. Radiolabeled zinc pyrithione was applied /dermally/ for 8 hr either as a single dose (50,100, and 400 mg/kg) or as a 5 day repeated dose (100 mg/kg). Serial samples of blood, urine, and feces were taken after dosing. Radioassay of necropsy material, urine, blood, and feces showed recovery of 86.8-98.2% of applied radioactivity. Greater than 90% of recovery was obtained from washings of the application site. Urinary excretion was 3% in animals with intact skin. Levels of radioactivity in blood, urine, and feces returned to background by 48 hours post-application. Dermal Absorption Factor: 3%. ...Less than 1% of administered zinc pyrithione is absorebed /through the skin/. Metabolism of zinc ... 2-Pyridinethiol 1-oxide has been investigated in Yorkshire pigs after IV admin. Within 96 hr ... 56% of zinc salt ... was excreted in urine. After IV admin in rabbits (14)C disappeared from blood rapidly, within 6 hr, 75% was excreted into urine while concentration of (65)Zn remained relatively constant with only 0.5% excreted into urine. Tissue concentration of (65)Zn were about 10 times higher than (14)C. Eight hr after dermal application, 0.5% of (14)C was excreted into urine, and same amount was found in major organs of rabbit. Less than 0.002% of applied (65)Zn was found in urine and 0.008% was found in major organs. For more Absorption, Distribution and Excretion (Complete) data for Pyrithione zinc (7 total), please visit the HSDB record page. Metabolism / Metabolites Zinc pyridinethione was biotransformed in rabbits, rats, monkeys, and dogs after oral dosing into 2-pyridinethiol 1-oxide S-glucuronide and 2-pyridinethiol S-glucuronide. Orally admin in rat (14)C-labeled zinc pyrithione's major route of elimination from the body was urine, minor metabolite was 2-mercaptopyridine-N-oxide, & major were S-glucuronides of 2-mercaptopyridine-N-oxide. 2-(Methylsulfonyl)pyridine was identified, minor serum metabolites were 2-(methylthio) pyridine 1-oxide, 2-(methylthio)pyridine, & 2-(methylsulfinyl)pyridine 1-oxide. Zinc can enter the body through the lungs, skin, and gastrointestinal tract. Intestinal absorption of zinc is controlled by zinc carrier protein CRIP. Zinc also binds to metallothioneins, which help prevent absorption of excess zinc. Zinc is widely distributed and found in all tissues and tissues fluids, concentrating in the liver, gastrointestinal tract, kidney, skin, lung, brain, heart, and pancreas. In the bloodstream zinc is found bound to carbonic anhydrase in erythrocytes, as well as bound to albumin, _2-macroglobulin, and amino acids in the the plasma. Albumin and amino acid bound zinc can diffuse across tissue membranes. Zinc is excreted in the urine and faeces. (L49) |
||
| Toxicity/Toxicokinetics |
Toxicity Summary Anaemia results from the excessive absorption of zinc suppressing copper and iron absorption, most likely through competitive binding of intestinal mucosal cells. Unbalanced levels of copper and zinc binding to Cu,Zn-superoxide dismutase has been linked to amyotrophic lateral sclerosis (ALS). Stomach acid dissolves metallic zinc to give corrosive zinc chloride, which can cause damage to the stomach lining. Metal fume fever is thought to be an immune response to inhaled zinc. (L48, L49, A49) Toxicity Data LD50: 177 mg/kg (Oral, Rat) (L545) LD50: 100 mg/kg (Dermal, Rabbit) (L545) LC50: 140 mg/m3 over 4 hours (Inhalation, Rat) (L545) Interactions In mice infected with Staphylococcus aureus strain exhibiting resistance to penicillin, Omnadin Z when given in combination with penicillin g sodium incr the antibiotic effect considerably, combination had stimulating effect on the immune response. DMSO (dimethylsulfoxide) aided the percutaneous penetration of zinc pyrithione in comparison with water, as evidenced by earlier onset of toxic signs. Non-Human Toxicity Values LD50 Rat male oral 630 mg/kg /Technical grade zinc pyrithione/ LD50 Rat female oral 460 mg/kg /Technical grade zinc pyrithione/ LD50 Rat (female) oral 177 mg/kg LD50 Rat (male) oral 207 mg/kg For more Non-Human Toxicity Values (Complete) data for Pyrithione zinc (9 total), please visit the HSDB record page. |
||
| References |
[1]. Ermolayeva, E. and D. Sanders, Mechanism of pyrithione-induced membrane depolarization in Neurospora crassa. Appl Environ Microbiol, 1995. 61(9): p. 3385-90. [2]. Copper induces cell death by targeting lipoylated TCA cycle proteins. Science. 2022 Mar 18;375(6586):1254-1261. |
||
| Additional Infomation |
Zinc pyrithione is a fine beige granules. (NTP, 1992) Pyrithione Zinc is a coordination complex of the zinc ion and pyrithione, a derivative of the naturally occurring antibiotic aspergillic acid with antimicrobial, antifungal and anti-seborrheic effects. Although the exact mechanism of action remains to be fully elucidated, pyrithione zinc appears to interfere with the membrane transport of ions and metabolites, ultimately leading to a loss of metabolic control. In addition, this agent causes an influx of copper, leading to a reduction in the activity of iron-sulphur proteins resulting in growth inhibition. Zinc pyrithione is a chemical compound of zinc. It is used as an antifungal and antibacterial agent. Zinc is a metallic element with the atomic number 30. It is found in nature most often as the mineral sphalerite. Though excess zinc in harmful, in smaller amounts it is an essential element for life, as it is a cofactor for over 300 enzymes and is found in just as many transcription factors. (L48, L49, L76) See also: Pyrithione (has active moiety); Biotin; pyrithione zinc (component of); Pyrithione zinc; salicylic acid (component of) ... View More ... Therapeutic Uses Keratolytic Agents /Pyrithione zinc/ effectiveness in dandruff and seborrhea is purported to result from both /cytostatic and antifungal/ actions and ... residual adherence to the skin after shampoo and rinse. An international questionnaire completed by 722 dermatologists assessed the belief of tachyphylaxis incidence with pyrithione zinc (PTZ)-based shampoos, time course, occurrence relative to active ingredients, and effect of switching products. Two double-blind, randomized, clinical evaluations were conducted, 24- and 48-week studies, whereby a 1% PTZ shampoo, a 2% PTZ shampoo, or a matched placebo control shampoo was used by each subject for the duration of the study. Dermatologists assessed the adherent scalp flaking (scale of 0-10) at baseline and at specified intervals. 64% of responding dermatologists believed tachyphylaxis occurred with PTZ products, and most felt that tachyphylaxis occurred within 3 months of use. Evaluation of mean treatment responses vs. placebo and individual responses as a function of study duration showed a consistent benefit for all products at all time points; therefore, no evidence for tachyphylaxis was found (within 48 weeks of treatment) ... Dandruff results from at least three etiologic factors: Malassezia fungi, sebaceous secretions, and individual sensitivity ... Of the three etiologic factors implicated in dandruff, Malassezia, sebaceous triglycerides, and individual susceptibility, Malassezia are the easiest to control. Pyrithione zinc kills Malassezia and all other fungi, and is highly effective against the Malassezia species actually found on scalp. Reduction in fungi reduces free fatty acids, thereby reducing scalp flaking and itch. ... The efficacy and safety of ketoconazole (KET) 2% and zinc pyrithione (ZPT) 1% in shampoo formulations for the alleviation of severe dandruff and seborrheic dermatitis /were compared/. This open randomized, parallel-group trial began with a 2-week run-in phase during which subjects applied a neutral non-antidandruff shampoo. It was followed by a 4-week randomized treatment phase and a subsequent 4-week follow-up phase without treatment. Shampooing during the treatment period was carried out twice weekly for the KET group and at least twice weekly for the ZPT group in accordance with the label instructions. A total of 343 subjects were recruited to enter the trial. Of the 331 eligible volunteers, 171 were randomized to KET 2% and 160 to ZPT 1%. ... Beneficial effects were evidenced for both medicated shampoos, but the effect was significantly better for KET 2%, which achieved a 73% improvement in the total dandruff severity score compared with 67% for ZPT 1% at week 4 (p < 0.02). The recurrence rate of the disease was also significantly lower following KET 2% treatment than following ZPT 1% treatment ... Both formulations were well tolerated. Drug Warnings A patient had had stable psoriasis for 25 years and no any other skin disease. Within 20 days, she developed an aggravated scaly erythematous patch on the scalp, where /an antidandruff/ shampoo had been applied, and simultaneously developed pustular psoriasis on both forearms. Patch testing showed a relevant sensitization to zinc pyrithione, and ... symptomatic aggravation by provocation testing with zinc pyrithione shampoo /was observed/... A case of allergic contact dermatitis to a shampoo containing zinc pyrithione associated with an eruption of pustular psoriasis is reported. The patient had had stable psoriasis for 5 years, and never any other skin disease. Within 1 week she developed severe generalized pustular psoriasis with many lesions where the shampoo was applied. Treatment with cyclosporin, 200 to 300 mg daily, cleared the eruption within 4 weeks, except for psoriasis of the scalp. Extensive patch testing revealed a relevant sensitization to zinc pyrithione ... Zinc Pyrithione is a broad-spectrum antimicrobial agent commonly used in antifungal and antibacterial formulations (e.g., skincare, hair care products) [1][2] Its core mechanisms of action include: inducing plasma membrane depolarization and ion imbalance in fungi (Neurospora crassa) by disrupting membrane ion transport [1]; modulating copper ion homeostasis in mammalian cells to enhance copper-mediated targeting of lipoylated TCA cycle proteins, leading to metabolic dysfunction, ROS accumulation, and cell death [2] It exhibits weak inherent cytotoxicity to mammalian cells but acts as a synergistic agent with copper ions, potentiating copper-induced cell death in cancer cells [2] In environmental microbiology, it is used to inhibit fungal growth via membrane disruption, while its potential in cancer therapy is explored through synergistic interaction with copper [1][2] |
Solubility Data
| Solubility (In Vitro) |
|
|||
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.87 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1476 mL | 15.7381 mL | 31.4762 mL | |
| 5 mM | 0.6295 mL | 3.1476 mL | 6.2952 mL | |
| 10 mM | 0.3148 mL | 1.5738 mL | 3.1476 mL |