Synthesis, characterization, molecular docking studies of new alkyl derivatives of 5-(2-bromo-4-fluorophenyl)-4-ethyl-4H- -1,2,4-triazole-3-thiol.

The main goal of this article is to present the results of the synthesis of new alkyl derivatives of 5-(2-bromo4-fluorophenyl)-4-ethyl-4H-1,2,4-triazole-3-thiol and molecular docking studies against COX-1 and COX-2. Previous studies have established a wide range of biological activity of 1,2,4-triazole derivatives. Therefore, it was essential to determine how a new series of 1,2,4-triazole derivatives would provide potential anti-inflammatory activity. To reach the goal, raw alkyl derivatives of 5-(2-bromo-4-fluorophenyl)-4-ethyl-4H-1,2,4-triazole-3-thiols (2a-2i) from 5-(2-bromo-4-fluorophenyl)-4-ethyl-4H-1,2,4-triazole3-thiol (1e) were obtained. The structure of the synthesized compounds was confirmed by 1H-NMR elemental analyses. The individuality and purity of compounds were confirmed by the method of liquid chromatography-mass spectrometry. These compounds have a relatively simple synthesis scheme, which gives them an advantage in creating a potential drug, and the appearance of alkyl radicals in the molecule should positively affect pharmacokinetic indicators, stability, selectivity, and bioavailability. An in silico study was conducted for the synthesized compounds, namely molecular docking, in relation to the interaction with COX-1 and COX-2. Based on the selectivity indexes of binding modes observed for the selected compounds (2e, 2g) with active COX-1 centers, it was found that compounds can reliably exhibit their anti-inflammatory effect through the prostaglandin biosynthesis pathway, inhibiting COX-1 instead of COX-2. The effect of hydrophobic interactions of alkyl groups of 1,2,4-triazole derivatives on changes in affinity and selectivity to COX-1 or COX-2 has also been proven. Therefore, derivatives of 1,2,4 are promising candidates for improvement, further study, and future development of new, more powerful antiinflammatory drugs for therapeutic use.

The Physicochemical and Antibacterial Properties of Chitosan-Based Materials Modified with Phenolic Acids Irradiated by UVC Light.

This paper concerns the physicochemical properties of chitosan/phenolic acid thin films irradiated by ultraviolet radiation with wavelengths between 200 and 290 nm (UVC) light. We investigated the preparation and characterization of thin films based on chitosan (CTS) with tannic (TA), caffeic (CA) and ferulic acid (FA) addition as potential food-packaging materials. Such materials were then exposed to the UVC light (254 nm) for 1 and 2 h to perform the sterilization process. Different properties of thin films before and after irradiation were determined by various methods such as Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), atomic force microscopy (AFM), differential scanning calorimeter (DSC), mechanical properties and by the surface free energy determination. Moreover, the antimicrobial activity of the films and their potential to reduce the risk of contamination was assessed. The results showed that the phenolic acid improving properties of chitosan-based films, short UVC radiation may be used as sterilization method for those films, and also that the addition of ferulic acid obtains effective antimicrobial activity, which have great benefit for food packing applications.

The Preparation and Characterization of Chitosan-Based Hydrogels Cross-Linked by Glyoxal.

In this study, hydrogels based on chitosan cross-linked by glyoxal have been investigated for potential medical applications. Hydrogels were loaded with tannic acid at different concentrations. The thermal stability and the polyphenol-releasing rate were determined. For a preliminary assessment of the clinical usefulness of the hydrogels, they were examined for blood compatibility and in the culture of human dental pulp cells (hDPC). The results showed that after immersion in a polyphenol solution, chitosan/glyoxal hydrogels remain nonhemolytic for erythrocytes, and we also did not observe the cytotoxic effect of hydrogels immersed in tannic acid (TA) solutions with different concentration. Tannic acid was successfully released from hydrogels, and its addition improved material thermal stability. Thus, the current findings open the possibility to consider such hydrogels in clinics.

The role of microorganisms in biodegradation of chitosan/tannic acid materials.

High utilization of thermoplastic polymers with low degradation rates as packaging materials generates a large amount of waste. Therefore, it should be replaced by natural polymers that can be degraded by microorganisms. In this paper, chitosan (CTS)/tannic acid (TA) materials in the weight ratios of 80CTS/20TA and 50CTS/50TA were prepared as potential packaging materials. The results showed that these materials were similarly degraded in soil and compost. However, in comparison to 50CTS/50TA, 80CTS/20TA was slightly better degraded in soil. After 14 days of biodegradation, the chemical structure of materials was changed resulting from adhesion of the microorganisms. The smallest changes were observed on 80CTS/20TA film. Bacterial species were collected and identified from materials after the degradation process. Microorganisms with the highest hydrolytic activity were chosen for the degradation study. Biodegradation and hydrolytic activity were observed only in a few strains, which indicate difficulties in material degradation. Soil bacteria degraded the films better than bacteria isolated from the compost. This study showed also that consortia of bacteria added to soil and compost had a positive effect on the biodegradation of the tested materials and increased the biodegradation of these materials in the studied environments.

Development of tannic acid-enriched materials modified by poly(ethylene glycol) for potential applications as wound dressing.

The interests in the biomedical impact of tannic acid (TA) targeting production of various types of biomaterials, such as digital microfluids, chemical sensors, wound dressings, or bioimplants constantly increase. Despite the significant disadvantage of materials obtained from natural-based compounds and their low stability and fragility, therefore, there is an imperative need to improve materials properties by addition of stabilizing formulas. In this study, we performed assessments of thin films over TA proposed as a cross-linker to be used in combination with polymeric matrix based on chitosan (CTS), i.e. CTS/TA at 80:20 or CTS/TA at 50:50 and poly(ethylene glycol) (PEG) at the concentration of 10% or 20%. We evaluated their mechanical parameters as well as the cytotoxicity assay for human bone marrow mesenchymal stem cells, human melanotic melanoma (MNT-1), and human osteosarcoma (Saos-2). The results revealed significant differences in dose-dependent of PEG regarding the maximum tensile strength (σmax) or impact on the metabolic activity of tissue culture plastic. We observed that PEG improved mechanical parameters prominently, decreased the hemolysis rate, and did not affect cell viability negatively. Enclosed data, confirmed also by our previous reports, will undoubtedly pave the path for the future application of tannic acid-based biomaterials to treat wound healing.

Collagen-Based Materials Modified by Phenolic Acids-A Review.

Collagen-based biomaterials constitute one of the most widely studied types of materials for biomedical applications. Low thermal and mechanical parameters are the main disadvantages of such structures. Moreover, they present low stability in the case of degradation by collagenase. To improve the properties of collagen-based materials, different types of cross-linkers have been researched. In recent years, phenolic acids have been studied as collagen modifiers. Mainly, tannic acid has been tested for collagen modification as it interacts with a polymeric chain by strong hydrogen bonds. When compared to pure collagen, such complexes show both antimicrobial activity and improved physicochemical properties. Less research reporting on other phenolic acids has been published. This review is a summary of the present knowledge about phenolic acids (e.g., tannic, ferulic, gallic, and caffeic acid) application as collagen cross-linkers. The studies concerning collagen-based materials with phenolic acids are summarized and discussed.

Properties of scaffolds based on chitosan and collagen with bioglass 45S5.

Scaffolds based on chitosan (CTS), collagen (Coll) and glycosaminoglycans (GAG) mixtures cross-linked by tannic acid (TA) with bioglass 45S5 addition were obtained with the use of the freeze-drying method. The prepared scaffolds were characterised for morphology, mechanical strength and degradation rate. Moreover, cell viability on the obtained scaffolds was measured with and without the presence of ascorbic acid and dexamethasone. The main purpose of the research was to compare the effectiveness of bioglass 45S5 influence on the physicochemical and biological properties of scaffolds. The results demonstrated that the scaffolds based on the blends of biopolymers cross-linked by TA are stable in an aqueous environment. Scanning electron microscope images allowed the observation of a porous scaffold structure with interconnected pores. The addition of bioglass nanoparticles improved the mechanical properties and decreased the degradation rate of composite materials. The biological properties were improved for 20% tannic acid addition compared to 5%. However, the addition of bioglass 45S5 did not change to cells response significantly.