Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents) - Volume 19, Issue 1, 2020

Background: One of the many debated topics in inflammation research is whether this scenario is really an accelerated form of human wound healing and immunityboosting or a push towards autoimmune diseases. The answer requires a better understanding of the normal inflammatory process, including the molecular pathology underlying the possible outcomes. Exciting recent investigations regarding severe human inflammatory disorders and autoimmune conditions have implicated molecular changes that are also linked to normal immunity, such as triggering factors, switching on and off, the influence of other diseases and faulty stem cell homeostasis, in disease progression and development. Methods: We gathered around and collected recent online researches on immunity, inflammation, inflammatory disorders and AMPK. We basically searched PubMed, Scopus and Google Scholar to assemble the studies which were published since 2010. Results: Our findings suggested that inflammation and related disorders are on the verge and interfere in the treatment of other diseases. AMPK serves as a key component that prevents various kinds of inflammatory signaling. In addition, our table and hypothetical figures may open a new door in inflammation research, which could be a greater therapeutic target for controlling diabetes, obesity, insulin resistance and preventing autoimmune diseases. Conclusion: The relationship between immunity and inflammation becomes easily apparent. Yet, the essence of inflammation turns out to be so startling that the theory may not be instantly established and many possible arguments are raised for its clearance. However, this study might be able to reveal some possible approaches where AMPK can reduce or prevent inflammatory disorders.

Introduction: Hemodialysis stands out as an eligible treatment for patients with chronic kidney disease. The subsequent inflammatory process resulting from this disease and hemodialysis per se is exacerbated in this therapy. Selenium (Se) is an essential trace element that can participate in the inhibition of pro-oxidant and pro-inflammatory processes and could be considered a measurement that indicates the progression of chronic kidney disease and inflammation. Objectives: The present study investigated selenemia in hemodialysis patients of the ABC region of São Paulo and aimed to establish the correlation between an inflammatory marker and selenemia in this conditions disease. Methods: This is an observational cross-sectional study of the Faculdade de Medicina do ABC in patients submitted to hemodialysis three times a week for at least six months. The eligible group composed of 21 patients, who filled out forms and underwent biochemical tests (colorimetric enzyme methods, flow cytometer, turbidimetric method and mass spectrometry). Results: The study population showed, women (70%), men (30%) with a mean age of 47 ± 17 years, Caucasians (36%) and non-Caucasian (64%), hypertensive (68%), smokers (53%) and non-smokers (64%). There was a hegemonic prevalence of systolic arterial hypertension (SAH) 68.1% in relation to diabetes mellitus (DM) (50%). Pre and post hemodialysis (HD) selenemia showed statistical significance, which did not occur with Creactive protein. There was a predominance of females in our sample; the pre- and post- HD selenemia were within the normal range of the reference values; there was a statistically significant correlation between pre and post-HD selenemia; there was no correlation with statistical significance between values of pre and post-HD C-reactive protein. Conclusion: Our data showed that there was no direct relationship between pre- and post- HD inflammation and pre- and post-HD selenemia.

Background: Hydroxytriazenes and their derivatives have been studied for the biological and pharmacological applications in the past few years. These compounds possess antibacterial, antifungal, anti-inflammatory, analgesic and wound healing activities. In this study, we report the synthesis of ten hydroxytriazenes in two series derived from disubstituted aniline and studied for antimicrobial and anti-inflammatory activities. Methods: For this purpose, 2-methyl-5-chloroaniline and 2-trifluoromethyl-5-chloroaniline were used to synthesize compounds A1-5 and B1-5 series, respectively. All compounds were synthesized by the reported method which involves three steps of the method (i) Reduction, (ii) Diazotization, (iii) Coupling. All synthesized compounds were characterized by various techniques CHN elemental analysis, FTIR, 1H NMR, and MASS spectral analysis. The antibacterial activities of the compounds were screened against S. aureus, S. pyogenes, E. coli, P. aeruginosa, and antifungal activities were against C. albicans, A. clavatus by the zone of inhibition method. In addition, anti-inflammatory activity was also evaluated by carrageenan-induced paw edema method and results were reported as % inhibition. Results: All the synthesized compounds were obtained in pure form and their spectral data are in good agreement with their structure. The synthesized compounds have shown good antimicrobial activity and zone of inhibition was ranging 21 to 24 mm. Further antiinflammatory effect of the compounds was 96.58 to 98.71 % inhibition. Conclusion: The results of the present study indicate that chloro and trifluoromethyl substitution at hydroxytriazenes skeleton could improve anti-inflammatory and antimicrobial activities.

Background: (Quinazoline-4-ylidene)hydrazides are valued intermediates in modern organic chemistry, as they are commonly used for the synthesis of substituted [1,2,4]triazolo[1,5-c]quinazolines. Objective: Unknown N-acyl-2-([1,2,4]triazolo[1,5-c]quinazoline-2-yl)-alkyl-(alkaryl-, aryl-) amines were synthesized and evaluated for anti-inflammatory potential. Methods: The peculiarities of the synthesized compounds structures were studied by IR-, NMR spectroscopy and chromatography-mass spectrometry and were discussed in detail. Probable molecular mechanisms of activity (inhibition of COX-1 and COX-2) were predicted due to molecular docking. Anti-inflammatory activity of synthesized compounds was determined by their ability to reduce the formalin-induced paw edema in rats. Diclofenac sodium was used as reference drug. Results: In this study, the synthesis of N-acetyl-(benzoyl)-2-([1,2,4]triazolo[1,5-c]quinazolinе- 2-yl)alkyl-(aralkyl-, aryl-)amines, using (3H-quinazoline-4-ylidene)hydrazides of Nprotected amino acids or 4-hydrazinoquinazoline and N-prorotected amino acids as starting compounds was developed. It was established that the reaction of (3H-quinazoline-4- ylidene)hydrazides of Boc-amino acids occurred with the formation of N-acetyl-substituted triazoloquinazolines. High anti-inflammatory activity was detected for unknown (3Hquinazoline- 4-ylidene)hydrazides Boc-amino acids (1.13-1.15) and N-acetyl-(benzoyl)-2- ([1,2,4]triazolo[1,5-c]quinazoline-2-yl-)aralkyl-(aryl-)amines (3.2, 3.3, 3.11, 3.12), using the experimental formalin test. Conclusion: The conducted SAR-analysis allowed to detect critical fragments. Namely, the Boc-aminoaralkyl-(aryl-)acid residue in (3H-quinazoline-4-ylidene)hydrazides (1.13- 1.15), benzyl and phenyl linker groups in N-acetyl-(benzoyl)-2-([1,2,4]triazolo[1,5- c]quinazoline-2-yl-)aralkyl-(aryl-) amines (3.2, 3.3, 3.11, 3.12) are believed to be substantial for anti-inflammatory activity.

Background: Persistent oxidative stress can lead to chronic inflammation and mediate most chronic diseases including neurological disorders. Oleuropein has been shown to be a potent antioxidant molecule in olive oil leaf having antioxidative properties. Objective: The aim of this study was to investigate the protective effects of oleuropein against oxidative stress in human glioblastoma cells. Methods: Human glioblastoma cells (U87) were pretreated with oleuropein (OP) essential oil 10 μM. After 30 minutes, 100 μM H2O2 was added to the cells for three hours. Cell survival was quantified by colorimetric MTT assay. Glutathione level, total oxidant capacity, total antioxidant capacity and nitric oxide levels were determined by using specific spectrophotometric methods. The relative gene expression level of iNOS was performed by qRT-PCR method. Results: According to viability results, the effective concentration of H2O2 (100μM) significantly decreased cell viability and oleuropein pretreatment significantly prevented the cell losses. Oleuropein regenerated total antioxidant capacity and glutathione levels decreased by H2O2 exposure. In addition, nitric oxide and total oxidant capacity levels were also decreased after administration of oleuropein in treated cells. Conclusion: Oleuropein was found to have potent antioxidative properties in human glioblastoma cells. However, further studies and validations are needed in order to understand the exact neuroprotective mechanism of oleuropein.