1-Hydroxypyridine-2-thione zinc salt

A sensitive ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method has been developed and validated for simultaneous quantification of zinc pyrithione (ZPT) and climbazole (CBZ) deposited onto human scalp from anti-dandruff (AD) shampoos. Scrubbing with a buffer solution was used as the sampling method for the extraction of ZPT and CBZ from scalp. Derivatization of ZPT was carried out prior to UHPLC-MS/MS analysis. The identification of ZPT and CBZ was performed by examining ratios of selected multiple reaction monitoring (MRM) transitions in combination with UHPLC retention times. The limit of detection for ZPT and CBZ was established to be 1 and 2ng/mL, respectively. This sensitivity enables the quantification of ZPT and CBZ at deposition levels in the low ng/cm(2) range. The method was successfully applied for the analysis of scalp buffer scrub samples from an in vivo study. The levels of ZPT and CBZ deposited on the scalp at different time points after application of the AD shampoo were measured.

Zinc pyrithione (ZPT) is an active material that has been used for over 50 years to effectively treat dandruff and seborrheic dermatitis (D/SD). It has become the most common material for that purpose, its use has expanded to include other skin benefits such as skin hygiene. However, there is much about ZPT that is unappreciated. It is a rationally developed molecule that was modeled after the naturally occurring antimicrobial aspergillic acid. The molecular basis for its antifungal activity has been elucidated. The efficacy of ZPT originates from two attributes. First, it has a very broad antimicrobial spectrum of activity, including fungi, gram-positive and -negative bacteria. Second, the material has very low solubility, resulting in formulation and delivery as a particulate material, which has distinct performance advantages. The particles are deposited and retained on the target skin surfaces even when delivered from rinse-off products.

Oral squamous cell carcinoma (OSCC) patients diagnosed in late stages have limited chemotherapeutic options, underscoring the great need for development of new anticancer agents for more effective disease management. We aimed to identify novel anticancer agents for OSCC using quantitative high throughput assays for screening six chemical libraries consisting of 5170 small molecule inhibitors. In depth characterization resulted in identification of pyrithione zinc (PYZ) as the most effective cytotoxic agent inhibiting cell proliferation and inducing apoptosis in OSCC cells in vitro. Further, treatment with PYZ reduced colony forming, migration and invasion potential of oral cancer cells in a dose-dependent manner. PYZ treatment also led to altered expression of several key components of the major signaling pathways including PI3K/AKT/mTOR and WNT/β-catenin in OSCC cells. In addition, treatment with PYZ also reduced expression of 14-3-3ζ, 14-3-3σ, cyclin D1, c-Myc and pyruvate kinase M2 (PKM2), proteins identified in our earlier studies to be involved in development and progression of OSCCs.