Rapid determination of uracil in biological fluids at mercury thin film electrode for early detection of potential 5-fluorouracil toxicity due to dihydropyrimidine dehydrogenase deficiency.

Determination of plasma uracil was reported as a method for evaluation of Dihydropyrimidine dehydrogenase (DPD) activity that is highly demanded to ensure the safe administration of 5-fluorouracil (5-FU)-based therapies to cancer patients. This work reports the development of a simple electroanalytical method based on adsorptive stripping square wave voltammetry (AdSWV) at mercury film-coated glassy carbon electrode (MF/GCE) for the highly sensitive determination of uracil in biological fluids that can be used for diagnosis of decreased DPD activity. Due to the formation of the HgII-Uracil complex at the electrode surface, the accuracy of the measurement was not affected by the complicated matrices in biological fluids including human serum, plasma, and urine. The high sensitivity of the developed method results in a low limit of detection (≈1.3 nM) in human plasma samples, falling below the practical cut-off level of 15 ng mL-1 (≈0.14 µM). This threshold concentration is crucial for predicting 5-FU toxicity, as reported in buffer, and ≤1.15% in biological samples), and accuracy (recovery percentage close to 100%).

Synthesis, anti-inflammatory activity, inverse molecular docking, and acid dissociation constants of new naphthoquinone-thiazole hybrids.

Chronic Inflammation is associated with various types of diseases that involves pro-inflammatory cytokines like IL-6 and TNF-α. High costs and serious side effects of available anti-inflammatory/immunomodulatory drugs led us to design new compounds with promising anti-inflammatory activities. Many drugs and biologically important compounds involve naphthoquinone and thiazole moieties in their core structures. Thereby, here we report the synthesis, characterization and anti-inflammatory activities of new naphthoquinone thiazole hybrids by reaction of naphthoquinone acyl thioureas with various α-bromoketone derivatives. The position of NO2 group in one of the phenyl rings of naphthoquinone thiazole hybrids was changed while different substituents were introduced at the para position of the second phenyl ring. All compounds were tested for potential immunomodulatory effect. No inflammatory cytokines were observed in the absence of LPS stimulant. On the other hand, they had promising anti-inflammatory immunomodulatory activities by being able to decrease the production of the pro-inflammatory cytokines (TNF-α and IL-6) in the LPS-stimulated cells. In an effort to find the possible mechanism of action, several enzymes involved in signalling pathways that play critical roles in inflammatory responses were screened in silico. Subsequent to inverse molecular docking approach, PI3K was predicted be the potential target. The docked complexes of the most potent compounds 5g and 5i were subjected to molecular dynamics simulation to assess the binding stability of the igands with the putative target. Acid dissociation constants (pKa) of the products were also determined potentiometrically.

Analytical Methods for Determination of Antiviral Drugs in Different Matrices: Recent Advances and Trends.

Viruses are the main pathogenic substances that cause severe diseases in humans and other living things. They are among the most common microorganisms, and consequently, antiviral drugs have emerged to prevent and treat viral infections. Antiviral drugs are an essential drug group considering their prescription and consumption rates for different diseases and indications. Therefore, it is crucial to develop accurate and precise analytical methods to detect antiviral drugs in various matrices. Chromatographic techniques are used frequently for the quantification purpose since they allow simultaneous determination of antivirals. Electrochemical methods have also gained importance since the analysis can be performed quickly without the need for pretreatment. Spectrophotometric and spectrofluorimetric methods are used because they are simple, inexpensive, and less time-consuming methods. The purpose of this review is to present an overview of the analysis of currently used antiviral drugs from 2010 to 2021. Since studies on antiviral drugs are numerous, selected publications were reviewed in this article. The analysis of antiviral drugs was divided into three main groups: chromatographic, spectrometric, and electrochemical methods which were applied to different matrices, including pharmaceutical, biological, and environmental samples.