41 research outputs found

    Synergistic biomedical potential and molecular docking analyses of coumarin–triazole hybrids as tyrosinase inhibitors: design, synthesis, in vitro profiling, and in silico studies

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    The tyrosinase enzyme has a vital role in the browning of vegetables and fruits and the biosynthesis of melanin. In this work, we synthesized a diverse library of coumarin–triazole hybrids, and these compounds were characterized by using suitable analytical techniques. Our research work extends beyond the synthetic effort to explore the therapeutic potential of these compounds. We put the synthesized compounds through meticulous in vitro screening against the tyrosinase enzyme, and these coumarin derivatives evinced good IC50 values in the range of 0.339 ± 0.25 ”M to 14.06 ± 0.92 ”M. In the library of synthesized compounds, six compounds were found to be more potent than standard ascorbic acid (IC50 = 11.5 ± 1.00), and among them, 17e and 17f, being the most active, exhibited remarkable anti-tyrosinase potential, with IC50 values of 0.339 ± 0.25 ÎŒM and 3.148 ± 0.23 ÎŒM, respectively. Furthermore, an in silico modeling study was carried out to determine the key interactions of these compounds with the tyrosinase protein (PDB ID: 2Y9X) and thus to authenticate our experimental findings. The quantitative SAR studies exhibited a good correlation between the synthesized derivatives of coumarin and their anti-tyrosinase activity. The docking studies verified the experimental results, and ligand 17e showed good interaction with the core residues of tyrosinase. This study not only expands the field of coumarin–triazole hybrid synthesis but also provides valuable insights for the development of novel tyrosinase inhibitors

    P66shc and its downstream Eps8 and Rac1 proteins are upregulated in esophageal cancers

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    Members of Shc (src homology and collagen homology) family, p46shc, p52shc, p66shc have known to be related to cell proliferation and carcinogenesis. Whereas p46shc and p52shc drive the reaction forward, the role of p66shc in cancers remains to be understood clearly. Hence, their expression in cancers needs to be evaluated carefully so that Shc analysis may provide prognostic information in the development of carcinogenesis. In the present study, the expression of p66shc and its associate targets namely Eps8 (epidermal pathway substrate 8), Rac1 (ras-related C3 botulinum toxin substrate1) and Grb2 (growth factor receptor bound protein 2) were examined in fresh tissue specimens from patients with esophageal squamous cell carcinoma and esophageal adenocarcinoma using western blot analysis. A thorough analysis of both esophageal squamous cell carcinoma and adenocarcinoma showed p66shc expression to be significantly higher in both types of carcinomas as compared to the controls. The controls of adenocarcinoma show a higher basal expression level of p66shc as compared to the controls of squamous cell carcinoma. The expression level of downstream targets of p66shc i.e., eps8 and rac1 was also found to be consistently higher in human esophageal carcinomas, and hence correlated positively with p66shc expression. However the expression of grb2 was found to be equal in both esophageal squamous cell carcinoma and adenocarcinoma. The above results suggest that the pathway operated by p66shc in cancers does not involve the participation of Ras and Grb2 as downstream targets instead it operates the pathway involving Eps8 and Rac1 proteins. From the results it is also suggestive that p66shc may have a role in the regulation of esophageal carcinomas and represents a possible mechanism of signaling for the development of squamous cell carcinoma and adenocarcinoma of esophagus

    Discovery of novel 1,2,4-triazole tethered ÎČ-hydroxy sulfides as bacterial tyrosinase inhibitors: synthesis and biophysical evaluation through in vitro and in silico approaches

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    In this study, a series of 1,2,4-triazole-tethered ÎČ-hydroxy sulfide scaffolds 11a–h was synthesized in good to remarkable yields (69–90%) through the thiolysis of oxiranes by the thiols in aqueous basic catalytic conditions. The synthesized 1,2,4-triazole-tethered ÎČ-hydroxy sulfides were screened against bacterial tyrosinase enzyme, and Gram-positive and Gram-negative bacterial cultures i.e., (S. aureus) Staphylococcus aureus & (E. coli) Escherichia coli. Among the synthesized derivatives, the molecules 11a (IC50 = 7.67 ± 1.00 ÎŒM), 11c (IC50 = 4.52 ± 0.09 ÎŒM), 11d (IC50 = 6.60 ± 1.25 ÎŒM), and 11f (IC50 = 5.93 ± 0.50 ÎŒM) displayed the better tyrosinase inhibitory activity in comparison to reference drugs ascorbic acid (IC50 = 11.5 ± 1.00 ÎŒM) and kojic acid (IC50 = 30.34 ± 0.75 ÎŒM). The molecule benzofuran-triazol-propan-2-ol 11c proved to be the most potent bacterial tyrosinase inhibitory agent with a minimum IC50 of 4.52 ± 0.09 ÎŒM, as compared to other synthesized counterparts and both standards (kojic acid and ascorbic acid). The compound diphenyl-triazol-propan-2-ol 11a and benzofuran-triazole-propan-2-ol 11c showed comparable anti-bacterial chemotherapeutic efficacy with minimum inhibitory concentrations (MIC = 2.0 ± 2.25 mg mL−1 and 2.5 ± 0.00 mg mL−1, respectively) against S. aureus bacterial strain in comparison with standard antibiotic penicillin (MIC = 2.2 ± 1.15 mg mL−1). Furthermore, among the synthesized derivatives, only compound 11c demonstrated better anti-bacterial activity (MIC = 10 ± 0.40 mg mL−1) against E. coli, which was slightly less than the standard antibiotic i.e., penicillin (MIC = 2.4 ± 1.00 mg mL−1). The compound 11c demonstrated a better binding score (−7.08 kcal mol−1) than ascorbic acid (−5.59 kcal mol−1) and kojic acid (−5.78 kcal mol−1). Molecular docking studies also validate the in vitro anti-tyrosinase assay results; therefore, the molecule 11c can be the lead bacterial tyrosinase inhibitor as well as the antibacterial agent against both types of bacterial strains after suitable structural modifications

    Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

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    Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

    Bioactive peptides from egg: a review

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    Edible packaging systems for improved microbial quality of animal-derived foods and the role of emerging technologies

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    International audienceAnimal-derived foods are susceptible to microbial spoilage due to their superior nutritional composition and high moisture content. Among the various options, edible packaging is a relatively nascent area and can effectively control microbial growth without substantially affecting the sensory and techno-functional properties. Numerous studies have evaluated the effect of edible packaging systems on the microbial quality of animal-derived foods, however, a review that specifically covers the effect of edible packaging on animal foods and summarizes the findings of these studies is missing in the literature. To fill this gap, the present review analyses the findings of the studies on animal foods published during the last five years. Studies have reported edible-packaging systems for improving microbial stability of animal foods using different biopolymers (proteins, polysaccharides, lipids, and their derivatives) and bioactive ingredients (phytochemicals, peptides, plant extracts, essential oils, and their nanoparticles, nanoemulsions or coarse emulsions). In general, nanoparticles and nanoemulsions are more effective in controlling microbial spoilage in animal foods compared to the direct addition of bioactive agents to the film matrices. Studies have reported the use of non-thermal and emerging technologies in combination with edible packaging systems for improved food safety or their use for enhancing functionality, bioactivity and characteristics of the packaging systems. Future studies should focus on developing sustainable packaging systems using widely available biopolymers and bioactive ingredients and should also consider the economic feasibility at the commercial scale

    Cricket protein hydrolysates pre-processed with ultrasonication and microwave improved storage stability of goat meat emulsion

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    International audienceThe study was designed to evaluate the potential of cricket protein hydrolysates as a novel food bio-preservative using goat meat emulsion as a food-model system. The efficacy of the hydrolysates was improved using mi-crowave (T1) and ultrasonication (T2) as pre-treatments before hydrolysis of cricket protein using alcalase enzyme (3% w/w). Both the pre-treatments caused a significant increase in the antioxidant and antimicrobial potential of the hydrolysates. The hydrolysates were added to the emulsion at the maximum level of 2.0% and analysed for quality for two weeks storage (4 +/- 1 degrees C) compared to the control samples. The effect of digestion simulation was also evaluated on the emulsion samples. A significant positive effect of the pre-treated hydro-lysates was observed on the storage stability (antioxidant potential, lipid stability, protein oxidation, microbial stability, and sensory quality). The digestion simulation significantly increased the radical-scavenging and ion -reducing activity of the meat emulsion, improving its functional value and health-promoting properties
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