2-Pyridinethiol 1-oxide

Absorption

Following oral ingestion, only the pyrithione moiety is absorbed. Less than 1% of administered zinc pyrithione is absorbed from the skin . Radioabeled Zn pyrithione administered to rats, rabbits and monkeys, either orally or via intraperitoneal injection were absorbed into circulatin to extent of 80-90% .

Toxicity

Acute oral LD50 value is 177 mg/kg in rat and 160 mg/kg in mouse. Acute dermal LD50 was 100 mg/kg in rabbit .

Chemical properties

off-white powder

The Uses of 2-Pyridinethiol 1-oxide

2-Mercaptopyridine N-oxide is used in ratiometric fluorescence imaging of intracellular zinc ions in mammalian cultures. It is used in the radical coupling of benzoyl derivatives of 2-deoxy-D-ribose, with heterocyclic bases to give C-nucleosides. It acts as a ligand and form coordination complexes with palladium chloride. It is a precursor to O-acyl thiohydroxamates. Further, it serves as an antifungal agent. In addition to this, it is used in the preparation of 1-oxa-2-oxo-3-thia-indolizinium chloride by reaction with carbonyl dichloride.

The Uses of 2-Pyridinethiol 1-oxide

Precursor to O-acyl thiohydroxamates. Ligates to metals to form biologically active complexes.

Indications

Indicated for the treatment of dandruff and seborrheic dermatitis .

Background

Pyrithione zinc, or zinc pyrithione or zinc pyridinethione, is a coordination complex consisted of pyrithione ligands chelated to zinc (2+) ions via oxygen and sulfur centers. In the crystalline state, it exists as a centrosymmetric dimer. Due to its dynamic fungistatic and bacteriostatic properties, pyrithione zinc is used to treat dandruff and seborrheic dermatitis. Dandruff is a common scalp disease affecting >40% of the world's adult population, and may be caused by fungi such as Malassezia globosa and M. restricta .
Pyrithione zinc is commonly found as an active ingredient in OTC antidandruff topical treatments such as shampoos. It mediates its action by increasing the cellular levels of copper, and damaging iron-sulfur clusters of proteins essential for fungal metabolism and growth . Due to low solubility, pyrithione zinc released from the topical formulations is deposited and retained relatively well onto the target skin surfaces . Other uses of pyrithione zinc include additive in antifouling outdoor paints and algaecide. While its use has been approved in the early 1960's by the FDA , safety and effectiveness of pyrithione zinc has been reported for decades. It is not shown to have any significant estrogenic activity according to the in vivo and in vitro assays .

Definition

ChEBI: Pyrithione is a pyridinethione that is pyridine-2(1H)-thione in which the hydrogen attached to the nitrogen is replaced by a hydroxy group. It is a Zn(2+) ionophore; the zinc salt is used as an antifungal and antibacterial agent. It has a role as an ionophore. It is a pyridinethione and a monohydroxypyridine. It is a tautomer of a pyridine-2-thiol N-oxide.

General Description

2-Mercaptopyridine N-oxide forms complexes on reaction with palladium chloride. It inhibits NADH-fumarate reductase purified from Trypanosoma cruzi. It is precursor to O-acyl thiohydroxamates. It ligates to metals to form biologically active complexes.

Pharmacokinetics

Pyrithione zinc has a broad antimicrobial spectrum of activity, including fungi, gram-positive and gram-negative bacteria . Pyrithione zinc is effective against Malassezia and all other fungi, especially the Malassezia species found on scalp . In patients with dandruff, treatment with pyrithione zinc reduced the amount of fungus on the scalp, which reduces the amount of free fatty acids, thereby reducing scalp flaking and itch .

Metabolism

After oral administration in rabbits, rats, monkeys, and dogs, pyrithione zinc is biotransformed into 2-pyridinethiol 1-oxide S-glucuronide and 2-pyridinethiol S-glucuronide .