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Diabetes mellitus has become a major global health burden because of several related consequences, including heart disease, retinopathy, cataracts, metabolic syndrome, collapsed renal function, and blindness. In the recent study, thirty Schiff base derivatives of 1,3-diphenylurea were synthesized and their anti-diabetic activity was evaluated by targeting α-glucosidase. The compounds exhibited an overwhelming inhibitory potential for α-glucosidase with higher potency ranging from 2.49-37.16 µM. The most effective compound, 5h, showed competitive inhibition of α-glucosidase (K i = 3.96 ± 0.0048 µM) in the kinetic analysis and strong binding interactions with key residues α-glucosidase in docking analysis, indicating its potential for better glycemic control in diabetes patients.
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Essential oils are key ingredients in the development of edible films and provide a diverse approach to improving food preservation, as well as sensory qualities. The pectin and kappa-carrageenan composite films were obtained by adding peppermint essential oil in different quantities. The films after their fabrication were thoroughly evaluated for their attributes, which included mechanical, barrier, optical, chemical, thermal, and antioxidant properties. The visual assessment of the films demonstrated that PEO-loaded films showed a uniform, homogenous, and slightly yellowish appearance. There was an increase in the thickness (0.045 ± 0.006 to 0.060 ± 0.008 mm), elongation at break (12.73 ± 0.74 to 25.05 ± 1.33 %), and water vapor permeability (0.447 ± 0.014 to 0.643 ± 0.014 (g*mm)/(m2*h*kPa)) was observed with the addition of PEO. However, tensile strength (45.84 ± 3.69 to 29.80 ± 2.10 MPa) and moisture content (25.83 ± 0.046 to 21.82 ± 0.23 %) decreased with the incorporation of PEO. Furthermore, thermal and antioxidant properties were enhanced by the inclusion of PEO. The presented investigation can be employed to synthesize food packaging material with antioxidant properties with potential applications in food packaging.
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INTRODUCTION: Current medications for autoimmune disorders often induce broad-ranging side effects, prompting a growing interest in therapies with more specific immune system modulation. Pioglitazone, known for its anti-diabetic properties, is increasingly recognized for significant immunomodulatory potential. Beyond its traditional use in diabetes management, pioglitazone emerges as a promising therapeutic candidate for autoimmune disorders. AREAS COVERED: This comprehensive review explores pioglitazone's impact on four prominent autoimmune conditions: systemic lupus erythematosus, psoriasis, inflammatory bowel disease, and multiple sclerosis. We focus on pioglitazone's diverse effects on immune cells and cytokines in these diseases, highlighting its potential as a valuable therapeutic option for autoimmune diseases. Here we have reviewed the latest and most current research literature available on PubMed, based on research published in the last 15 years. EXPERT OPINION: Pioglitazone as an immunomodulatory agent can regulate T cell differentiation, inhibit inflammatory cytokines, and promote anti-inflammatory macrophages. While further clinical studies are needed to fully understand its mechanisms and optimize treatment strategies, pioglitazone represents a potential therapeutic approach to improve outcomes for patients with these challenging autoimmune conditions. The future of autoimmune disease research may involve personalized treatment approaches, and collaborative efforts to improve patient quality of life.
This article explores the potential use of pioglitazone, a medication commonly used to treat diabetes, for autoimmune disorders treatment. The focus of the review centers around the effects of pioglitazone on systemic lupus erythematosus, psoriasis, inflammatory bowel disease, and multiple sclerosis. In the case of systemic lupus erythematosus, pioglitazone appears to induce a shift in specific immune cells, leading to a reduction in systemic inflammation and damage to organs. In psoriasis, the medication shows promise in suppressing immune responses, thereby alleviating skin inflammation. For individuals with inflammatory bowel disease, pioglitazone seems to safeguard a protein with anti-inflammatory properties, aiding in the repair of bowel tissue. Regarding multiple sclerosis, pioglitazone appears to influence the behavior of immune cells and promote the restoration of nerve tissue. These diverse effects of pioglitazone on the immune system suggest its potential as a valuable treatment option for autoimmune diseases. However, it is important to note that further research is necessary to fully comprehend the mechanisms by which pioglitazone operates and to determine the optimal approaches for its utilization in clinical studies.
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This editorial introduces the potential of targeting macrophage function for diabetic cardiomyopathy (DCM) treatment by dipeptidyl peptidase-4 (DPP-4) inhibitors. Zhang et al studied teneligliptin, a DPP-4 inhibitor used for diabetes management, and its potential cardioprotective effects in a diabetic mouse model. They suggested teneligliptin administration may reverse established markers of DCM, including cardiac hypertrophy and compromised function. It also inhibited the NLRP3 inflammasome and reduced inflammatory cytokine production in diabetic mice. Macrophages play crucial roles in DCM pathogenesis. Chronic hyperglycemia disturbs the balance between pro-inflammatory (M1) and anti-inflammatory (M2) macrophages, favoring a pro-inflammatory state contributing to heart damage. Here, we highlight the potential of DPP-4 inhibitors to modulate macrophage function and promote an anti-inflammatory environment. These compounds may achieve this by elevating glucagon-like peptide-1 levels and potentially inhibiting the NLRP3 inflammasome. Further studies on teneligliptin in combination with other therapies targeting different aspects of DCM could be suggested for developing more effective treatment strategies to improve cardiovascular health in diabetic patients.
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Developing new anti-tyrosinase drugs seems crucial for the medical and industrial fields since irregular melanin synthesis is linked to the resurgence of several skin conditions, including melanoma, and the browning of fruits and vegetables. A novel series of N-1 and C-3 substituted indole-based thiosemicarbazones 5(a-r) are synthesized and further analyzed for their inhibition potential against tyrosinase enzyme through in vitro assays. The synthesized compounds displayed very good to moderate inhibition with half maximal inhibitory concentration in the range of 12.40 ± 0.26 µM to 47.24 ± 1.27 µM. Among all the derivatives 5k displayed the highest inhibitory activity. According to SAR analysis, the derivatives with 4-substitution at the benzyl or phenyl ring of the thiosemicarbazones exhibited better inhibitory potential against tyrosinase. In silico analysis (including ADMET prediction and molecular docking) was conducted and compared with the standard drug (kojic acid). These findings may help the hunt for new melanogenesis inhibitors that the food and cosmetics industries may find valuable.
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BACKGROUND: Carbon quantum dots (CQDs) have gained much interest recently for being efficient probes. Their cost-effectiveness, eco-friendliness, and unique photocatalytic activities made them distinctive alternatives to other luminescent approaches like fluorescent dyes and luminous derivatization. Meanwhile, delafloxacin (DLF) is a recently approved antibacterial medicine. DLF has been authorized for the treatment of soft-tissue and skin infections as well as pneumonia. Therefore, new eco-friendly, cost-effective, and sensitive tools are needed its estimation in different matrices. RESULTS: In the proposed study, green copper and nitrogen carbon dots (Cu-N@CDs) were synthesized from a green source (plum juice with copper sulphate). Cu-N@CQDs were then characterized using multiple tools including X-ray photon spectroscopy (XPS), FTIR and UV-VIS spectroscopy, Zeta potential measurements, High-resolution transmission electron microscopy (HRTEM), and fluorescence spectroscopy. After gradually adding DLF, the developed quantum dots' fluorescence was significantly enhanced within the working range of 0.5-100.0 ng mL-1. The limits of detection and quantification were 0.08 and 0.27 ng mL-1, respectively. The accuracy of the proposed method ranged from 96.00 to 99.12 % in recovery%, when recovered from milk and plasma samples. SIGNIFICANCE: Cu-N@CDs were utilized and validated for selectively determining DLF in several matrices including pharmaceutical forms, human plasma and in milk samples using spectrofluorimetric technique. The bio-analytical method is simple and could be used in content uniformity testing as well as in therapeutic drug monitoring in human plasma.
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Carbono , Cobre , Fluoroquinolonas , Nitrógeno , Puntos Cuánticos , Puntos Cuánticos/química , Nitrógeno/química , Cobre/química , Carbono/química , Fluoroquinolonas/análisis , Fluoroquinolonas/sangre , Fluoroquinolonas/química , Humanos , Animales , Fluorometría/métodos , Límite de Detección , Espectrometría de Fluorescencia , Leche/química , Antibacterianos/sangre , Antibacterianos/análisis , Antibacterianos/químicaRESUMEN
BACKGROUND: The Scutellaria genus has promising therapeutic capabilities as an aromatherapy. Based on that and local practices of S. nuristanica Rech. F. The essential oil was studied for the first time for its diverse biomedical applications. PURPOSE: This study aimed to evaluate and validate their therapeutic capabilities by screening the essential oil ingredients and examining their antimicrobial, antioxidant, carbonic anhydrase, and antidiabetic using further In silico assessment and In vivo anti-inflammatory and analgesic capabilities to devise novel sources as natural remedies alternative to the synthetic drugs. METHODS: Essential oil was obtained through hydrodistillation, and the constituents were profiled using GC-MS. The antimicrobial assessment was conducted using an agar well diffusion assay. Free radical scavenging capabilities were determined by employing DPPH and ABTS assay. The carbonic anhydrase-II was examined using colorimetric assay, while the antidiabetic significance was performed using α-Glucosidase assay. The anti-inflammatory significance was examined through carrageenan-induced paw edema, and the analgesic features of the essential oil were determined using an acetic acid-induced writhing assay. RESULTS: Fifty constituents were detected in S. nuristanica essential oil (SNEO), contributing 95.93 % of the total EO, with the predominant constituents being 24-norursa-3,12-diene (10.12 %), 3-oxomanoyl oxide (9.94 %), methyl 7-abieten-18-oate (8.85 %). SNEO presented significance resistance against the Gram-positive bacterial strains (GPBSs), Bacillus atrophaeus and Bacillus subtilis, as compared to the Salmonella typhi and Klebsiella pneumoniae, Gram-negative bacterial strains (GNBSs) as well as two fungal strains Aspergillus parasiticus and Aspergillus niger associated with their respective standards. Considerable free radical scavenging capacity was observed in DPPH compared to the ABTS assay when correlated with ascorbic acid. In addition, when equated with their standards, SNEO offered considerable in vitro carbonic anhydrase II and antidiabetic capabilities. Additionally, the antidiabetic behavior of the 9 dominant compounds of SNEO was tested via In silico techniques, such as molecular docking, which assisted in the assessment of the significance of binding contacts of protein with each chemical compound and pharmacokinetic evaluations to examine the drug-like characteristics. Molecular dynamic simulations at 100 ns and binding free energy evaluations such as PBSA and GBSA models explain the molecular mechanics and stability of molecular complexes. It was also observed that SNEO depicted substantial anti-inflammatory and analgesic capabilities. CONCLUSION: Hence, it was concluded that the SNEO comprises bioactive ingredients with biomedical significance, such as anti-microbial, antioxidant, CA-II, antidiabetic, anti-inflammatory, and analgesic agents. The computational validation also depicted that SNEO could be a potent source for the discovery of anti-diabetic drugs.
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Antiinflamatorios , Antioxidantes , Edema , Hipoglucemiantes , Aceites Volátiles , Scutellaria , Animales , Scutellaria/química , Antioxidantes/farmacología , Antioxidantes/química , Antiinflamatorios/farmacología , Antiinflamatorios/química , Aceites Volátiles/farmacología , Aceites Volátiles/química , Hipoglucemiantes/farmacología , Hipoglucemiantes/química , Edema/tratamiento farmacológico , Analgésicos/farmacología , Analgésicos/química , Masculino , Ratones , Simulación del Acoplamiento Molecular , Carragenina , Cromatografía de Gases y Espectrometría de Masas , Antiinfecciosos/farmacología , Antiinfecciosos/química , Aromaterapia/métodos , Antibacterianos/farmacología , Antibacterianos/químicaRESUMEN
The single-stranded RNA genome of SARS-CoV-2 encodes several structural and non-structural proteins, among which the papain-like protease (PLpro) is crucial for viral replication and immune evasion and has emerged as a promising therapeutic target. The current study aims to discover new inhibitors of PLpro that can simultaneously disrupt its protease and deubiquitinase activities. Using multiple computational approaches, six compounds (CP1-CP6) were selected from our in-house compounds database, with higher docking scores (-7.97 kcal/mol to -8.14 kcal/mol) and fitted well in the active pocket of PLpro. Furthermore, utilizing microscale molecular dynamics simulations (MD), the dynamic behavior of selected compounds was studied. Those molecules strongly binds at the PLpro active site and forms stable complexes. The dynamic motions suggest that the binding of CP1-CP6 brought the protein to a closed conformational state, thereby altering its normal function. In an in vitro evaluation, CP2 showed the most significant inhibitory potential for PLpro (protease activity = 2.71 ± 0.33 µM and deubiquitinase activity = 3.11 ± 0.75 µM), followed by CP1, CP5, CP4 and CP6. Additionally, CP1-CP6 showed no cytotoxicity at a concentration of 30 µM in the human BJ cell line.
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Proteasas Similares a la Papaína de Coronavirus , Enzimas Desubicuitinizantes , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , SARS-CoV-2 , SARS-CoV-2/enzimología , SARS-CoV-2/efectos de los fármacos , Humanos , Enzimas Desubicuitinizantes/metabolismo , Enzimas Desubicuitinizantes/química , Proteasas Similares a la Papaína de Coronavirus/química , Proteasas Similares a la Papaína de Coronavirus/metabolismo , Proteasas Similares a la Papaína de Coronavirus/antagonistas & inhibidores , Inhibidores de Proteasas/farmacología , Inhibidores de Proteasas/química , Dominio Catalítico , Proteasas 3C de Coronavirus/antagonistas & inhibidores , Proteasas 3C de Coronavirus/metabolismo , Proteasas 3C de Coronavirus/química , Antivirales/farmacología , Antivirales/química , Productos Biológicos/farmacología , Productos Biológicos/química , Tratamiento Farmacológico de COVID-19 , COVID-19/virología , Unión ProteicaRESUMEN
Tyrosinase inhibitors are studied in the cosmetics and pharmaceutical sectors as tyrosinase enzyme is involved in the biosynthesis and regulation of melanin, hence these inhibitors are beneficial for the management of melanogenesis and hyperpigmentation-related disorders. In the current work, a novel series of diphenyl urea derivatives containing a halo-pyridine moiety (5a-t) was synthesized via a multi-step synthesis. In vitro, tyrosinase inhibitory assay results showed that, except for two compounds, the derivatives were excellent inhibitors of human tyrosinase. The average IC50 value of the inhibitors (15.78 µM) is lower than that of kojic acid (17.3 µM) used as the reference compound, indicating that, on average, these molecules are more potent than the reference. Derivative 5a was identified as the most potent human tyrosinase inhibitor of the series, with an IC50 value of 3.5 ± 1.2 µM, approximately 5 times more potent than kojic acid. To get further insights into the nature of binding site interactions, molecular docking and molecular dynamics simulation studies were carried out. Moreover, the evaluation of in silico ADME properties showed a highly favorable profile for the synthesized compounds. These findings suggested that the further development of this class of compounds could be useful to get potent drug-like compounds that can target hyperpigmentation-related disorders.
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Inhibidores Enzimáticos , Simulación del Acoplamiento Molecular , Monofenol Monooxigenasa , Piridinas , Monofenol Monooxigenasa/antagonistas & inhibidores , Monofenol Monooxigenasa/metabolismo , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Humanos , Relación Estructura-Actividad , Piridinas/química , Piridinas/farmacología , Piridinas/síntesis química , Estructura Molecular , Relación Dosis-Respuesta a Droga , Urea/farmacología , Urea/análogos & derivados , Urea/química , Urea/síntesis química , Simulación de Dinámica MolecularRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Due to the high prevalence of cancer, researchers for the past decades have made considerable efforts for its management and treatment. Medicinal plants have always been exploited to discover novel anticancer agents. Oman's huge biodiversity has created a rich source of traditional medicine. OBJECTIVE: The current survey has aimed to document the traditionally used medicinal plants of Oman and their therapeutic role in the treatment of cancer. MATERIAL METHOD: This study comprises of literature-based survey through different databases, including Google, Scopus, Google Scholar, Web of Science, Science Direct, Springer Link, BioMed Central and PubMed. RESULTS: The current review revealed a total of 57 plant species that belong to 35 families that are used in the treatment of cancer in Oman. Most documented plants belong to Solanaceae (6 sp.), Apocyanaceae (5 sp.) and Lamiaceae (4 sp.). The literature reveals that the residents of the area mostly use leaves (38.5%) and prepare their recipes in the form of decoction (40.3%). Moreover, herbs are the most dominant life form (43.85%). Among all forms of cancer in Oman, breast (47%), wound (26), and lung cancer (0.5%) were found dominantly. A literature study confirmed that the medicinal plants used for cancer in Oman are rich in phytochemicals such as quercetin, allicin, coumarin, alliin, kaempferol, solamargine, rutin, lupeol, ursolic acid and luteolin that have shown significant biological activities including anti-cancer potential. It reflects the efficacy of these plants to be used as a medicine in clinical trials. Among all, Boswellia sacra Flueck. is of key importance due to the presence Boswellic acid being used for the treatment of different types of cancer. CONCLUSION: The residents of Oman have great knowledge about the traditional use of medicinal plants for the treatment of various diseases like cancer. The therapeutic potential and physiological efficacy of Omani medicinal plants should be further explored at a molecular level via in vivo and in vitro experiments.
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With the global increase in the use of dietary supplements to provide nutrients in one's regular diet, these supplements' potential health risks and benefits have become a topic of significant interest. Interestingly, as dietary supplements, the Food and Drug Administration (FDA) in the United States (USA), Europe, and most countries do not require manufacturers and distributors to obtain approval or provide safety assessments before marketing those products. This research explores for the first time 16 heavy, trace and macro-elemental contents, namely, As, Ni, Cd, Pb, Cu, Co, Mn, Cr, Zn, V, Fe, Al, K, Na, Mg, and Ca, within 24 nutraceutical and herbal supplements marketed in Oman. The research is focusing on ensuring their compositions, concentrations, and freedom of toxic elements. ICP-OES was utilized, preceded by a microwave digestion technique to digest the samples in concentrated HNO3 and HCl (3:1, v/v). The method was validated within linear ranges of 0.03-5.00 ppm and 1.0-200.0 ppm for micro- and macro-elements, respectively, with %recoveries ranging from 90 to 104%. The limits of detection ranged from 0.01 to 0.09 and 0.14 to 0.30 ppm, while the limits of quantification ranged from 0.03 to 0.28 and 0.46 to 0.91 ppm for micro- and macro-elements, respectively. The detected levels were compared to online databases for risk assessment. Although As and Cd were not detected in all samples, Pb was found in nine samples, with some exceeding regulated limits of exposure. About 80% of the samples contained Al, of which two samples were susceptible to serious health risks of exceeding exposure limits in their compiled doses. The locally harvested Omani herbal supplements revealed significant amounts of Zn, Mg, Mn, and Cu. The results highlighted the potential risks associated with both dosage compliance and labeling discrepancies.
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[This corrects the article DOI: 10.1016/j.heliyon.2024.e31671.].
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Prolyl oligopeptidase (POP) is a compelling therapeutic target associated with aging and neurodegenerative disorders due to its pivotal role in neuropeptide processing. Despite initial promise demonstrated by early-stage POP inhibitors, their progress in clinical trials has been halted at Phase I or II. This impediment has prompted the pursuit of novel inhibitors. The current study seeks to contribute to the identification of efficacious POP inhibitors through the design, synthesis, and comprehensive evaluation (both in vitro and in silico) of thiazolyl thiourea derivatives (5a-r). In vitro experimentation exhibited that the compounds displayed significant higher potency as POP inhibitors. Compound 5e demonstrated an IC50 value of 16.47 ± 0.54 µM, representing a remarkable potency. A meticulous examination of the structure-activity relationship indicated that halogen and methoxy substituents were the most efficacious. In silico investigations delved into induced fit docking, pharmacokinetics, and molecular dynamics simulations to elucidate the intricate interactions, orientation, and conformational changes of these compounds within the active site of the enzyme. Moreover, our pharmacokinetic assessments confirmed that the majority of the synthesized compounds possess attributes conducive to potential drug development.
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Simulación del Acoplamiento Molecular , Prolil Oligopeptidasas , Serina Endopeptidasas , Tiourea , Tiourea/química , Tiourea/farmacología , Tiourea/síntesis química , Tiourea/análogos & derivados , Relación Estructura-Actividad , Humanos , Serina Endopeptidasas/química , Serina Endopeptidasas/metabolismo , Simulación de Dinámica Molecular , Inhibidores de Serina Proteinasa/química , Inhibidores de Serina Proteinasa/farmacología , Inhibidores de Serina Proteinasa/síntesis química , Modelos Moleculares , Tiazoles/química , Tiazoles/farmacología , Tiazoles/síntesis química , Dominio Catalítico , Técnicas de Química SintéticaRESUMEN
Myocardial infarction (MI) is considered one of the most common cardiac diseases and major cause of death worldwide. The prevalence of MI and MI-associated mortality have been increasing in recent years due to poor lifestyle habits viz. residency, obesity, stress, and pollution. Synthetic drugs for the treatment of MI provide good chance of survival; however, the demand to search more safe, effective, and natural drugs is increasing. Plants provide fruitful sources for powerful antioxidant and anti-inflammatory agents for prevention and/or treatment of MI. However, many plant extracts lack exact information about their possible dosage, toxicity and drug interactions which may hinder their usefulness as potential treatment options. Phytoconstituents play cardioprotective role by either acting as a prophylactic or adjuvant therapy to the concurrently used synthetic drugs to decrease the dosage or relief the side effects of such drugs. This review highlights the role of different herbal formulations, examples of plant extracts and types of several isolated phytoconstituents (phenolic acids, flavonoids, stilbenes, alkaloids, phenyl propanoids) in the prevention of MI with reported activities. Moreover, their possible mechanisms of action are also discussed to guide future research for the development of safer substitutes to manage MI.
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Carbonic anhydrase CA-II enzyme is essential for maintaining homeostasis in several processes, including respiration, lipogenesis, gluconeogenesis, calcification, bone resorption, and electrolyte balance due to its vital function within cellular processes. Herein, we screened 25 newly synthesized thiazole derivatives and assessed their inhibitory potential against the zinc-containing carbonic anhydrase CA-II enzyme. Intriguingly, derivatives of thiazole exhibited varying degrees of inhibitory action against CA-II. The distinctive attribute of these compounds is that they can attach to the CA-II binding site and block its action. Morpholine based thiazoles can be strategically modified to improve bovine CA-II inhibitor binding affinity, selectivity, and pharmacokinetics. Thiazole and morpholine moieties can boost inhibitory efficacy and selectivity over other calcium-binding proteins by interacting with target bovine CA-II binding sites. The derivatives 23-26 exhibited greater affinity when compared to the standard acetazolamide. Furthermore, kinetic study of the most potent compound 24 was performed, which exhibited concentration dependent inhibition with a K i value of 9.64 ± 0.007 µM. Molecular docking, MD simulation and QSAR analysis was also carried out to elucidate the interactions, orientation, and conformational changes of these compounds within the active site of the enzyme. Moreover, pharmacokinetic assessments showed that most of the compounds possess attributes conducive to potential drug development.
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BACKGROUND: Aerobic glycolysis is crucial for cancer cells to survive, grow, and progress. In the current study, the anti-cancer effects of astragalin (ASG) on breast cancer cells and in the glycolytic pathway through AMPK/mTOR have been evaluated. OBJECTIVE: The objective of this study was to examine the impact of ASG, a natural flavonoid, on glycolysis via targeting AMPK/mTOR signalling in MDA-MB-231 breast cancer cells. METHOD: The study utilized ASG, which was isolated from Haplophyllum tuberculatum. The cells were treated with different concentrations of ASG (20 and 40 µg/mL), and anti- glycolytic activities were measured through cell proliferation, expression of glycolytic enzymes (HK-2, LDH-A, GLUT-1), glucose uptake, and lactate concentration assays. The MTT assay was used to assess cellular proliferation, while the glucose uptake and lactate levels were determined by employing colorimetric assays. The mRNA expression of target glycolytic enzymes was determined by qRT-PCR. The protein levels of glycolytic targets, as well as that of AMPK and mTOR, were determined by western blot. in silico docking of ASG was done with mTOR and AMPK proteins. RESULT: Astragalin exhibited dose- and time-dependent anti-proliferative effects in MDA-MB-231 cells. In breast cancer cells, the mRNA and protein expression of GLUT-1, LDH-A, and HK-2 were all significantly downregulated after receiving ASG treatments. Furthermore, after ASG treatments, MDA-MB231 cells showed a significant decrease in lactate and glucose uptake compared to control cells. Mechanistically, ASG increased AMPK activation and suppressed mTOR activation in these cells. The inhibitory role of ASG on aerobic glycolysis was prevented by treatments with compound C (an AMPK inhibitor). However, combined treatment of compound C and ASG could nullify the ASG-induced anti-glycolysis effect and restore the level of p-AMPK and p-mTOR in MDA-MB231 cells. The results from molecular docking predicted that ASG had the potential to bind AMPK and mTOR, with free energy for binding, -8.2 kcal/mol and -8.1 kcal/mol, respectively. CONCLUSION: Taken together, the findings from this study indicated that ASG might modulate the AMPK/mTOR pathway to inhibit aerobic glycolysis and proliferation of MDAMB231 breast cancer.
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A small library of 79 substituted phenylsulfonamidoalkyl sulfamates, 1b-79b, was synthesized starting from arylsulfonyl chlorides and amino alcohols with different numbers of methylene groups between the hydroxyl and amino moieties yielding intermediates 1a-79a, followed by the reaction of the latter with sulfamoyl chloride. All compounds were screened for their inhibitory activity on bovine carbonic anhydrase II. Compounds 1a-79a showed no inhibition of the enzyme, in contrast to sulfamates 1b-79b. Thus, the inhibitory potential of compounds 1b-79b towards this enzyme depends on the substituent and the substitution pattern of the phenyl group as well as the length of the spacer. Bulkier substituents in the para position proved to be better for inhibiting CAII than compounds with the same substituent in the meta or ortho position. For many substitution patterns, compounds with shorter spacer lengths were superior to those with long chain spacers. Compounds with shorter spacer lengths performed better than those with longer chain spacers for a variety of substitution patterns. The most active compound held inhibition constant as low as Ki = 0.67 µM (for 49b) and a tert-butyl substituent in para position and acted as a competitive inhibitor of the enzyme.
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Anhidrasa Carbónica II , Inhibidores de Anhidrasa Carbónica , Ácidos Sulfónicos , Anhidrasa Carbónica II/antagonistas & inhibidores , Anhidrasa Carbónica II/metabolismo , Inhibidores de Anhidrasa Carbónica/química , Inhibidores de Anhidrasa Carbónica/síntesis química , Inhibidores de Anhidrasa Carbónica/farmacología , Ácidos Sulfónicos/química , Animales , Bovinos , Relación Estructura-Actividad , Sulfonamidas/química , Sulfonamidas/farmacología , Sulfonamidas/síntesis química , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/síntesis química , Bibliotecas de Moléculas Pequeñas/farmacología , Estructura MolecularRESUMEN
BACKGROUND: Patient adherence to therapy and compliance is always a challenge for care providers in the management of chronic disorders with multiple medications. OBJECTIVE: Our study focused on formulating concurrently prescribed ARB (Angiotensin Receptor Blocker), i.e., losartan potassium, and a cholesterol-lowering statin derivative, i.e., rosuvastatin calcium, in a fixed-dose combination tablet. METHODS: The drugs were selected based on the presence of synergism and variation in solubility characteristics. Trial batches with fixed concentrations of both active pharmaceutical ingredients (APIs) and varying quantities of different excipients were prepared by dry granulation technique and subjected to different quality control tests for tablets. Batch F5 was selected on the basis of in-process quality control data for the development of a drug release protocol. Experimental conditions were optimized. Based on the sink condition, phosphate buffer (pH 6.8) was selected as the dissolution medium. Simultaneous determination of both APIs in samples collected at predetermined time intervals was carried out using the RP-HPLC technique with acetonitrile, methanol, and water (20:25:55 v/v/v) as mobile phase. RESULTS: Complete dissolution of both APIs in the FDC tablet was achieved in 45 min in 900 mL of the selected medium. The in vitro drug release protocol was validated for accuracy and precision without interference with sample analysis. CONCLUSION: In this study, a validated, accurate, and robust dissolution testing method was developed for the newly formulated FDC tablet.
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Combinación de Medicamentos , Liberación de Fármacos , Estabilidad de Medicamentos , Losartán , Rosuvastatina Cálcica , Comprimidos , Rosuvastatina Cálcica/administración & dosificación , Rosuvastatina Cálcica/química , Rosuvastatina Cálcica/farmacocinética , Losartán/química , Losartán/administración & dosificación , Losartán/análisis , Solubilidad , Cromatografía Líquida de Alta Presión , Inhibidores de Hidroximetilglutaril-CoA Reductasas/química , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificaciónRESUMEN
The study examined the antimicrobial and antioxidant potential of pure Acetyl-11-keto-ß-boswellic acid (AKBA), boswellic acid (70%) and AKBA loaded nanoparticles as topical polymeric films. The optimized concentration (0.05 % w/v) of pure AKBA, boswellic acid (BA), and AKBA loaded silver nanoparticles were used to study its impact on film characteristics. Carboxymethyl cellulose (CMC), sodium alginate (SA), and gelatin (Ge) composite films were prepared in this study. The polymeric films were evaluated for their biological (antioxidant and antimicrobial activities) and mechanical characteristics such as tensile strength (TS) and elongation (%). Moreover, other parameters including water barrier properties and color attributes of the film were also evaluated. Furthermore, assessments were conducted using analytical techniques like FTIR, XRD, and SEM. Surface analysis revealed that AgNP precipitation led to a few particles in the film structure. Overall, the results indicate a relatively consistent microstructure. Moreover, due to the addition of AKBA, BA, and AgNPs, a significant decrease in TS, moisture content, water solubility, and water vapor permeation was observed. The films transparency also showed a decreasing trend, and the color analysis revealed decreasing yellowness (b*) of the films. Importantly, a significant increase in antioxidant activity against DPPH free radicals and ABTS cations was observed in the CSG films. Additionally, the AgNP-AKBA loaded films displayed significant antifungal activity against C. albicans. Moreover, the molecular docking analysis revealed the inter-molecular interactions between the AKBA, AgNPs, and composite films. The docking results indicate good binding of AKBA and silver nanoparticles with gelatin and carboxymethyl cellulosemolecules. In conclusion, these polymeric films have potential as novel materials with significant antioxidant and antifungal activities.
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BACKGROUND: There is a need for healthcare providers to develop life-story review interventions to enhance the mental well-being and quality of life of older adults. The primary aim of this study is to examine the effects of telling their life stories and creating a life-story book intervention on QoL, depressive symptoms, and life satisfaction in a group of older adults in Oman. METHODS: A repeated-measures randomized controlled design was conducted in Oman. A total of 75 older adults (response rate = 40.1%) were randomly assigned to the intervention (n = 38) or control (n = 37) groups. Demographic data were collected as the baseline. Depression, life satisfaction, and quality of life scores were collected from each participant at weeks 1, 2, 3, 4, and 8. RESULTS: Their average age is 67.3 ± 5.5 years (range 60-82 years). There are more women (n = 50, 66.7%) than men. Over the 8 weeks, the intervention group exhibited a notable decrease in depression (intervention: 2.5 ± 1.2 vs. control: 5.3 ± 2.1, p < .001) but an increase in life satisfaction (24.6 ± 3.1 vs. 21.9 ± 6.1, p < .001) and quality of life (physical: 76.2 ± 12.7 vs. 53.6 ± 15.5, p < .001; psychological: 76.4 ± 12.1 vs. 59.9 ± 21.5, p < .001; Social relation: 78.3 ± 11.7 vs. 61.8 ± 16.6, p < .001; environment: 70.8 ± 10.2 vs. 58.6 ± 16.1, p < .001) compared to the control group. CONCLUSION: The life-story review intervention proved effective in diminishing depression and boosting life satisfaction and quality of life among the older sample within the 8-week study. Healthcare providers can apply such interventions to improve older adults' mental health and well-being.