Chemical analysis for small amounts of horseradish peroxidase using “porphyrinogen” as a chromogenic reagent

The properties of porphyrinogen as a new chromogenic reagent were examined. 5,10,15,20-Tetrahydro-tetraphenylporphyrinogen (TPPN) is changed to 5,10,15,20-tetraphenylporphine (TPP) by the oxidative reaction involving six electrons, and its formation of the porphine ring significantly increased the absorbance in the Soret band.The horseradish peroxidase (HRP) accelerated the oxidative reaction as a catalyst and the increment of absorbance depended upon the increase in the concentration of HRP. The reaction proceeded in the presence of dissolved oxygen and in the neighborhood of pH 7. Based on these findings, a chemical analysis by catalytic action using HRP was developed.In the procedure for this determination, the difference in absorbance at 419 nm (ΔA₄₁₉=A_s−A_b, where A_s and A_b are the absorbances of the sample solution containing HRP and the blank solution without HRP after 30 min, respectively), was measured. The determination range of HRP, which was obtained from the ΔA₄₁₉—HRP concentration curve, was 0.05-1.0 mg/l. The relative standard deviation in the median of the calibration curve was 3.19% (seven determinations), and the detection limit (S/N=3) was 29 ng/l. Furthermore, when the proposed method was applied to the enzyme immunoassay, bisphenol A (BPA) was selectively and sensitivity determined.     

Topological aspect of Chern--Simons p-branes

By generalizing the topological current of Abelian Chern--Simons (CS) vortices, we present a topological tensor current of CS p-branes based on the \phi -mapping topological current theory. It is revealed that CS p-branes are located at the isolated zeros of the vector field \phi(x), and the topological structure of CS p-branes is characterized by the winding number of the \phi-mappings. Furthermore, the Nambu--Goto action and the equation of motion for multi CS p-branes are obtained.     

Synthesis and Neurotropic Activity of New Heterocyclic Systems: Pyridofuro[3,2-d]pyrrolo[1,2-a]pyrimidines,Pyridofuro[3,2-d]pyrido[1,2-a]pyrimidines and Pyridofuro[3′,2′:4,5]pyrimido[1,2-a]azepines

Background: Neurotic disturbances, anxiety, neurosis-like disorders, and stress situations are widespread. Benzodiazepine tranquillizers have been found to be among the most effective antianxiety drugs. The pharmacological action of benzodiazepines is due to their interaction with the supra-molecular membrane GABA-a-benzodiazepine receptor complex, linked to the Cl-ionophore. Benzodiazepines enhance GABA-ergic transmission and this has led to a study of the role of GABA in anxiety. The search for anxiolytics and anticonvulsive agents has involved glutamate-ergic, 5HT-ergic substances and neuropeptides. However, each of these well-known anxiolytics, anticonvulsants and cognition enhancers (nootropics) has repeatedly been reported to have many adverse side effects, therefore there is an urgent need to search for new drugs able to restore damaged cognitive functions without causing significant adverse reactions. Objective: Considering the relevance of epilepsy diffusion in the world, we have addressed our attention to the discovery of new drugs in this field Thus our aim is the synthesis and study of new compounds with antiepileptic (anticonvulsant) and not only, activity. Methods: For the synthesis of compounds classical organic methods were used and developed. For the evaluation of biological activity some anticonvulsant and psychotropic methods were used. Results: As a result of multistep reactions 26 new, five-membered heterocyclic systems were obtained. PASS prediction of anticonvulsant activity was performed for the whole set of the designed molecules and probability to be active Pa values were ranging from 0.275 to 0.43. The studied compounds exhibit protection against pentylenetetrazole (PTZ) seizures, anti-thiosemicarbazides effect as well as some psychotropic effect. The biological assays evidenced that some of the studied compounds showed a high anticonvulsant activity by antagonism with pentylenetetrazole. The toxicity of compounds is low and they do not induce muscle relaxation in the studied doses. According to the study of psychotropic activity it was found that the selected compounds have an activating behavior and anxiolytic effects on the models of “open field” and “elevated plus maze” (EPM). The data obtained indicate the anxiolytic (anti-anxiety) activity of the derivatives of pyrimidines, especially pronounced in compounds 6n, 6b, and 7c. The studied compounds increase the latent time of first immobilization on the model of “forced swimming” (FST) and exhibit some antidepressant effect similarly to diazepam. Docking studies revealed that compound 6k bound tightly in the active site of GABA_A receptor with a value of the scoring function that estimates free energy of binding (ΔG) at −7.95 kcal/mol, while compound 6n showed the best docking score and seems to be dual inhibitor of SERT transporter as well as 5-HT_1A receptor. Conclusions: Тhe selected compounds have an anticonvulsant, activating behavior and anxiolytic effects, at the same time exhibit some antidepressant effect.     

Flavone-Rich Fractions and Extracts from Oroxylum indicum and Their Antibacterial Activities against Clinically Isolated Zoonotic Bacteria and Free Radical Scavenging Effects

Oroxylum indicum extracts from the seeds collected from Lampang and Pattani provinces in Thailand, and young fruits and flowers exhibited in vitro display antioxidant and antibacterial activities against clinically isolated zoonotic bacteria including Staphylococcus intermedius, Streptococcus suis, Pseudomonas aeruginosa, β-hemolytic Escherichia coli and Staphylococcus aureus. The orange crystals and yellow precipitates were obtained from the preparation processes of the seed extracts. The orange-red crystals from the seeds collected from Lampang province exhibited strong in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging effects (EC₅₀ value = 25.99 ± 3.30 μg/mL) and antibacterial effects on S. intermedius and β-hemolytic E. coli while the yellow precipitate from the same source exhibited only antioxidant activity. Quantitative analysis of phytochemicals in O. indicum samples by spectrophotometric and HPLC techniques showed that they contained different amounts of total phenolic, total flavonoid and three major flavones; baicalin, baicalein and chrysin contents. Young fruit extract, which contained low amounts of flavone contents, still promoted antibacterial effects against the tested bacteria with IC₅₀ values lower than 1 mg/mL and MIC values between 4 to 10 mg/mL in S. intermedius, S. aureus and S suis while higher IC₅₀ and MIC values against P. aeruginosa and β-hemolytic E. coli were found. From scanning electron microscopy, the extract of the young fruit of O. indicum promoted morphological changes in the bacterial cells by disrupting the bacterial cell walls, inducing leakage of the cellular content, and generating the abnormal accumulation of cells. The mechanism of action of the extract for this antibacterial effect may be the disruption of the cell membrane and abnormal cell aggregations. Regression analysis of the results suggests the correlation between total phenolic and total flavonoid contents and antioxidant and antibacterial effects. Baicalin was found to have a high correlation with an inhibitory effect against β-hemolytic E. coli while three unidentified peaks, which could be flavones, showed high correlations with an inhibitory effect against S. intermedius, S. suis, P. aeruginosa and S. aureus.     

Charge‐Tagged DNA Radicals in the Gas Phase Characterized by UV/Vis Photodissociation Action Spectroscopy

Adenosine radicals tagged with a fixed‐charge group were generated in the gas phase and structurally characterized by tandem mass spectrometry, deuterium labeling, and UV/Vis action spectroscopy. Experimental results in combination with Born–Oppenheimer molecular dynamics, ab initio, and excited‐state calculations led to unambiguous assignment of adenosine radicals as N‐7 hydrogen atom adducts. The charge‐tagged radicals were found to be electronically equivalent to natural DNA nucleoside radicals.     

Recent Clinical and Preclinical Studies of Hydroxychloroquine on RNA Viruses and Chronic Diseases: A Systematic Review

The rapid spread of the new Coronavirus Disease 2019 (COVID-19) has actually become the newest challenge for the healthcare system since, to date, there is not an effective treatment. Among all drugs tested, Hydroxychloroquine (HCQ) has attracted significant attention. This systematic review aims to analyze preclinical and clinical studies on HCQ potential use in viral infection and chronic diseases. A systematic search of Scopus and PubMed databases was performed to identify clinical and preclinical studies on this argument; 2463 papers were identified and 133 studies were included. Regarding HCQ activity against COVID-19, it was noticed that despite the first data were promising, the latest outcomes highlighted the ineffectiveness of HCQ in the treatment of viral infection. Several trials have seen that HCQ administration did not improve severe illness and did not prevent the infection outbreak after virus exposure. By contrast, HCQ arises as a first-line treatment in managing autoimmune diseases such as rheumatoid arthritis, lupus erythematosus, and Sjögren syndrome. It also improves glucose and lipid homeostasis and reveals significant antibacterial activity.