Oxiconazole Nitrate

The cGAS-STING pathway is a critical component of the innate immune response to cytosolic DNA, driving the production of type I interferons (IFNs) and pro-inflammatory cytokines. However, excessive activation of this pathway is associated with various autoimmune and inflammatory diseases. In this study, we evaluated the regulation of FDA-approved azole antifungal drugs on the cGAS-STING pathway. Among these drugs, oxiconazole, miconazole, and itraconazole demonstrate significant inhibitory effects, with oxiconazole showing the strongest activity. Our data demonstrates that oxiconazole significantly suppressed type I IFN production and downstream inflammatory responses in macrophages and fibroblasts stimulated with synthetic DNA or infected with HSV-1. Mechanistically, oxiconazole hindered STING trafficking via oxysterol-binding protein OSBP. Using the Listeria monocytogenes infection model and the Trex1^-/- mouse disease model, both representing in vivo models of inflammation driven by excessive cGAS-STING activation, we demonstrate that oxiconazole enhanced bacterial clearance and reduced tissue damage in the Listeria monocytogenes infection model. Moreover, oxiconazole treatment significantly alleviated multi-organ inflammation and normalized aberrant IFN responses in the Trex1^-/- autoimmune disease mouse model. These findings highlight the potential of oxiconazole as a promising therapeutic agent for STING-driven autoimmune and inflammatory diseases.

In this study, a simple, precise, accurate, and sensitive reversed-phase liquid-chromatog. method (RPLC) for the antimycotic drugs climbazole, oxiconazole, and sertaconazole was developed and validated, the compounds were quantified in com. preparations and their degradation profiles were determined by forced degradationAll chromatog. separations were performed on a Pinnacle DB Cyano (5 μm, 250 x 4.6 mm) column.Acetonitrile-water binary mixture (45:55, volume/volume) and pH 7.0 was used as mobile phase.System suitability tests were conducted to determine the suitability of the developed method conditions to the reference values and the results were found to be satisfactory.The validation of the developed RPLC method was performed using linearity, selectivity, accuracy, precision, and recovery parameters.Linear concentration ranges were determined for each compound and the correlation coefficients were found to be greater than 0.998.Limit-of-detection and limit-of-quantitation values were calculated for the studied drugs and the sensitivity and selectivity of the method were found to be sufficient.Quantification of the compounds was carried out in the topical creams and com. shampoos at the determined separation condition.Stress tests (also known as forced degradation) are performed by exposing compounds to extreme conditions in order to determine their degradation profile over a short period of time.Degradation studies under stress conditions play an important role in different processes of development and production of drugs and pharmaceutical products.The results of these studies are used to assess the degradation behaviors of drugs and to validate chromatog. anal. methods.Compounds were subjected to the International Conference of Harmonization- prescribed acidic, alk., oxidative, photolytic and thermal stress conditions, and their degradation behaviors were determined successfully.After all stress tests, the highest degradation for all compounds was observed in the oxidative condition.The developed RPLC method was successfully validated and it can be used in the routine anal. of the quantification and degradation of imidazole compounds and their com. products.