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

In this study, a series of 1,2,4-triazole-tethered ß-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 ß-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 µM), 11c (IC50 = 4.52 ± 0.09 µM), 11d (IC50 = 6.60 ± 1.25 µM), and 11f (IC50 = 5.93 ± 0.50 µM) displayed the better tyrosinase inhibitory activity in comparison to reference drugs ascorbic acid (IC50 = 11.5 ± 1.00 µM) and kojic acid (IC50 = 30.34 ± 0.75 µM). 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 µM, 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.

Photocatalytic Activity of BaAl2O4 for Water Purification.

Degradation of dyes under natural light sources is one of the most active research areas in basic science for greener technology. In this context, the photocatalytic activity of semiconductors has received massive attention in solving water treatment-related issues as these possess enormous potential for degrading organic impurities. Here, we report that barium aluminate (BaAl2O4, BAO), which has been extensively studied for photoluminescence applications, is found to be a highly potent candidate for photocatalytic activities. We have explored the degradation of dyes (meant for water purification) by using the photocatalytic properties of pure and Dy- and Yb-codoped BAO. Crystal structure, electron microscopy, and Raman analysis of the autocombustion-synthesized pure and codoped BAO samples revealed significant morphological changes such as increased particle size and stabilization of rod-like structures. UV-vis absorbance measurements confirm the presence of multiple bandgaps in the BAO samples, which is substantiated by X-ray absorption spectroscopy measurements. Photocatalytic degradation studies of methylene blue (MB) dye (with different catalyst concentrations, dopings, and MB dye concentrations) have been carried out by using BAO. The kinetics of the photocatalytic degradation measurements has been explained by the Boltzmann distribution function, and the fastest (in less than 40 min), with more than 99% degradation of MB impurity, is reported here for the first time in BAO compounds. Synthesized BAO samples show excellent cyclic stability, which is essential for their potential applications in environmental remediation. The trade-off between the enhancement of surface area and increased particle size is considered the key parameter for controlling the photocatalytic performance of the BAO catalyst after Dy and Yb codopings.

Bio synthesis, comprehensive characterization, and multifaceted therapeutic applications of BSA-Resveratrol coated platinum nanoparticles.

This study examines the manufacturing, characterization, and biological evaluation of platinum nanoparticles, which were synthesized by Enterobacter cloacae and coated with Bovine Serum Albumin (BSA) and Resveratrol (RSV). The formation of PtNPs was confirmed with the change of color from dark yellow to black, which was due to the bioreduction of platinum chloride by E. cloacae. BSA and RSV functionalization enhanced these nanoparticles' biocompatibility and therapeutic potential. TGA, SEM, XRD, and FTIR were employed for characterization, where PtNPs and drug conjugation-related functional groups were studied by FTIR. XRD confirmed the crystalline nature of PtNPs and Pt-BSA-RSV NPs, while TGA and SEM showed thermal stability and post-drug coating morphological changes. Designed composite was also found to be biocompatible in nature in hemolytic testing, indicating their potential in Biomedical applications. After confirmation of PtNPs based nanocaompsite synthesis, they were examined for anti-bacterial, anti-oxidant, anti-inflammatory, and anti-cancer properties. Pt-BSA-RSV NPs showed higher concentration-dependent DPPH scavenging activity, which measured antioxidant capability. Enzyme inhibition tests demonstrated considerable anti-inflammatory activity against COX-2 and 15-LOX enzymes. In in vitro anticancer studies, Pt-BSA-RSV NPs effectively killed human ovarian cancer cells. This phenomenon was demonstrated to be facilitated by the acidic environment of cancer, as the drug release assay confirmed the release of RSV from the NP formulation in the acidic environment. Finally, Molecular docking also demonstrated that RSV has strong potential as an anti-oxidant, antibacterial, anti-inflammatory, and anticancer agent. Overall, in silico and in vitro investigations in the current study showed good medicinal applications for designed nanocomposites, however, further in-vivo experiments must be conducted to validate our findings.

Exploring theophylline-1,2,4-triazole tethered N-phenylacetamide derivatives as antimicrobial agents: unraveling mechanisms via structure-activity relationship, in vitro validation, and in silico insights.

Theophylline, a nitrogen-containing heterocycle, serves as a promising focal point for medicinal researchers aiming to create derivatives with diverse pharmacological applications. In this work, we present an improved synthetic method for a range of theophylline-1,2,4-triazole-S-linked N-phenyl acetamides (4a‒g) utilizing ultrasound-assisted synthetic approach. The objective was to assess the effectiveness of synthesized theophylline-1,2,4-triazoles (4a‒g) as inhibitors of HCV serine protease and as antibacterial agents against B. subtilis QB-928 and E. coli AB-274. Theophylline-1,2,4-triazoles were obtained in good to excellent yields (69%-95%) in a shorter time than conventional approach. 4-Chlorophenyl moiety containing theophylline-1,2,4-triazole 4c displayed significantly higher inhibitory activity against HCV serine protease enzyme (IC50 = 0.015 ± 0.25 mg) in comparison to ribavirin (IC50 = 0.165 ± 0.053 mg), but showed excellent binding affinity (-7.55 kcal/mol) with the active site of serine protease, better than compound 4c (-6.90 kcal/mol) as well as indole-based control compound 5 (-7.42 kcal/mol). In terms of percentage inhibition of serine protease, 2-chlorophenyl compound 4b showed the maximum percentage inhibition (86%), more than that of the 3,4-dichlorophenyl compound 4c (76%) and ribavirin (81%). 3,4-Dimethylphenyl-based theophylline-1,2,4-triazole 4g showed the lowest minimum inhibitory concentration (MIC = 0.28 ± 0.50 µg/mL) against the B. subtilis bacterial strain as compared to the standard drug penicillin (MIC = 1 ± 1.50 µg/mL). The other 4-methylphenyl theophylline-1,2,4-triazole 4e (MIC = 0.20 ± 0.08 µg/mL) displayed the most potent antibacterial potential against E. coli in comparison to the standard drug penicillin (MIC = 2.4 ± 1.00 µg/mL). Molecular docking studies further helped in an extensive understanding of all of the interactions between compounds and the enzyme active site, and DFT studies were also employed to gain insights into the molecular structure of the synthesized compounds. The results indicated that theophylline-linked triazole derivatives 4b and 4c showed promise as leading contenders in the fight against the HCV virus. Moreover, compounds 4e and 4g demonstrated potential as effective chemotherapeutic agents against E. coli and B. subtilis, respectively. To substantiate these findings, additional in vivo studies and clinical trials are imperative, laying the groundwork for their integration into future drug design and development.

Prevalence and predictors of discharge polypharmacy in geriatric patients discharged from an Indonesian teaching hospital: a retrospective observational study / Prevalencia y predictores de polifarmacia al alta en pacientes geriátricos dados de alta de un hospital universitario de Indonesia: un estudio observacional retrospectivo

Objective: The study aimed to investigate the prevalence and risk factors for discharge polypharmacy in geriatric patients in Indonesia. Methods: The retrospective cohort study used the medical record profiles of geriatric patients aged ≥ 60 years admitted to the inpatient ward between July 2018 and October 2019. Using three logistic regression models, we assessed the association of the patient’s demographic, clinical characteristics, and disease condition with discharge polypharmacy. The use of five or more medications was defined as discharge polypharmacy. Results: A total of 1533 patients were included in the study. Most patients (78.21%) aged between 60 and 74 years. The male-to-female patient ratio was almost the same (50.16% versus 49.83%). Of the patients (52.51%) were discharged with polypharmacy. According to regression model I, patients who had a chronic condition, comorbidity, stayed in the hospital for ≥ seven days, had a Charlson comorbidity index score (3-4), and received excessive polypharmacy (≥ 10 drugs) during admission had significantly more risk (p< 0.05) to receive polypharmacy at discharge. The results of model II investigated myocardial infarction, congestive heart failure, peripheral vascular disease, cerebrovascular disease, chronic obstructive pulmonary disease, diabetes mellitus, diabetes with complications, renal disease, and high blood pressure as significant (p<0.05) predictors of discharge polypharmacy. The combined model III evaluated that comorbidity, length of hospital stay (7 or more days), excessive polypharmacy use in the hospital, myocardial infarction, and congestive heart failure were significantly (P < 0.05) associated with discharge polypharmacy. Conclusions: Polypharmacy is common in Indonesia and is linked to certain chronic conditions and other clinical factors. A particular plan that includes a pharmacist and physician collaborative relationship and awareness of the health outcomes of polypharmacy could be critical.(AU)

Temperature drives microbial communities in anaerobic digestion during biogas production from food waste.

Resource depletion and climate changes due to human activities and excessive burning of fossil fuels are the driving forces to explore alternatives clean energy resources. The objective of this study was to investigate the potential of potato peel waste (PPW) at various temperatures T15 (15 °C), T25 (25 °C), and T35 (35 °C) in anaerobic digestion (AD) for biogas generation. The highest biogas and CH4 production (117 mL VS-g and 74 mL VS-g) was observed by applying 35 °C (T35) as compared with T25 (65 mL VS-g and 22 mL VS-g) on day 6. Changes in microbial diversity associated with different temperatures were also explored. The Shannon index of bacterial community was not significantly affected, while there was a positive correlation of archaeal community with the applied temperatures. The bacterial phyla Firmicutes were strongly affected by T35 (39%), whereas Lactobacillus was the dominant genera at T15 (27%). Methanobacterium and Methanosarcina, as archaeal genera, dominated in T35 temperature reactors. In brief, at T35, Proteiniphilum and Methanosarcina were positively correlated with volatile fatty acids (VFAs) concentration. Spearman correlation revealed dynamic interspecies interactions among bacterial and archaeal genera; facilitating the AD system. This study revealed that temperature variations can enhance the microbial community of the AD system, leading to increased biogas production. It is recommended for optimizing the AD of food wastes.

Herbal-based therapeutics for diabetic patients with SARS-Cov-2 infection.

Human SARS Coronavirus-2 (SARS-CoV-2) has infected more than 170 million people worldwide, being responsible for about 3.5 million deaths so far. Despite ongoing investigations, there is still more to understand the mechanism of COVID-19 infection completely. However, it has been evidenced that SARS-CoV-2 can cause Coronavirus disease (COVID-19) notably in diabetic people. Approximately 35% of the patients who died of this disease had diabetes. A growing number of studies have evidenced that hyperglycemia is a significant risk factor for severe SARS-CoV-2 infection and plays a key role in COVID-19 mortality and diabetes comorbidity. The uncontrolled hyperglycemia can produce low-grade inflammation and impaired immunity-mediated cytokine storm that fail multiple organs and sudden death in diabetic patients with SARS-CoV-2 infection. More importantly, SARS-CoV-2 infection and interaction with ACE2 receptors also contribute to pancreatic and metabolic impairment. Thus, using of diabetes medications has been suggested to be beneficial in the better management of diabetic COVID-19 patients. Herbal treatments, as safe and affordable therapeutic agents, have recently attracted a lot of attention in this field. Accordingly, in this review, we intend to have a deep look into the molecular mechanisms of diabetic complications in SARS-CoV-2 infection and explore the therapeutic potentials of herbal medications and natural products in the management of diabetic COVID-19 patients based on recent studies and the existing clinical evidence.

Temperature-dependent transformation of microbial community: A systematic approach to analyzing functional microbes and biogas production.

The stability and effectiveness of the anaerobic digestion (AD) system are significantly influenced by temperature. While majority research has focused on the composition of the microbial community in the AD process, the relationships between functional gene profile deduced from gene expression at different temperatures have received less attention. The current study investigates the AD process of potato peel waste and explores the association between biogas production and microbial gene expression at 15, 25, and 35 °C through metatranscriptomic analysis. The production of total biogas decreased with temperature at 15 °C (19.94 mL/g VS), however, it increased at 35 °C (269.50 mL/g VS). The relative abundance of Petrimonas, Clostridium, Aminobacterium, Methanobacterium, Methanothrix, and Methanosarcina were most dominant in the AD system at different temperatures. At the functional pathways level 3, α-diversity indices, including Evenness (Y = 5.85x + 8.85; R2 = 0.56), Simpson (Y = 2.20x + 2.09; R2 = 0.33), and Shannon index (Y = 1.11x + 4.64; R2 = 0.59), revealed a linear and negative correlation with biogas production. Based on KEGG level 3, several dominant functional pathways associated with Oxidative phosphorylation (ko00190) (25.09, 24.25, 24.04%), methane metabolism (ko00680) (30.58, 32.13, and 32.89%), and Carbon fixation pathways in prokaryotes (ko00720) (27.07, 26.47, and 26.29%), were identified at 15 °C, 25 °C and 35 °C. The regulation of biogas production by temperature possibly occurs through enhancement of central function pathways while decreasing the diversity of functional pathways. Therefore, the methanogenesis and associated processes received the majority of cellular resources and activities, thereby improving the effectiveness of substrate conversion to biogas. The findings of this study illustrated the crucial role of central function pathways in the effective functioning of these systems.

Synthesis, Cytotoxic, and Computational Screening of Some Novel Indole-1,2,4-Triazole-Based S-Alkylated N-Aryl Acetamides.

Molecular hybridization has emerged as the prime and most significant approach for the development of novel anticancer chemotherapeutic agents for combating cancer. In this pursuit, a novel series of indole-1,2,4-triazol-based N-phenyl acetamide structural motifs 8a-f were synthesized and screened against the in vitro hepatocellular cancer Hep-G2 cell line. The MTT assay was applied to determine the anti-proliferative potential of novel indole-triazole compounds 8a-f, which displayed cytotoxicity potential as cell viabilities at 100 µg/mL concentration, by using ellipticine and doxorubicin as standard reference drugs. The remarkable prominent bioactive structural hybrids 8a, 8c, and 8f demonstrated good-to-excellent anti-Hep-G2 cancer chemotherapeutic potential, with a cell viability of (11.72 ± 0.53), (18.92 ± 1.48), and (12.93 ± 0.55), respectively. The excellent cytotoxicity efficacy against the liver cancer cell line Hep-G2 was displayed by the 3,4-dichloro moiety containing indole-triazole scaffold 8b, which had the lowest cell viability (10.99 ± 0.59) compared with the standard drug ellipticine (cell viability = 11.5 ± 0.55) but displayed comparable potency in comparison with the standard drug doxorubicin (cell viability = 10.8 ± 0.41). The structure-activity relationship (SAR) of indole-triazoles 8a-f revealed that the 3,4-dichlorophenyl-based indole-triazole structural hybrid 8b displayed excellent anti-Hep-G2 cancer chemotherapeutic efficacy. The in silico approaches such as molecular docking scores, molecular dynamic simulation stability data, DFT, ADMET studies, and in vitro pharmacological profile clearly indicated that indole-triazole scaffold 8b could be the lead anti-Hep-G2 liver cancer therapeutic agent and a promising anti-Hep-G2 drug candidate for further clinical evaluations.

An Exploration of the Inhibitory Mechanism of Rationally Screened Benzofuran-1,3,4-Oxadiazoles and-1,2,4-Triazoles as Inhibitors of NS5B RdRp Hepatitis C Virus through Pharmacoinformatic Approaches.

Benzofuran, 1,3,4-oxadiazole, and 1,2,4-triazole are privileged heterocyclic moieties that display the most promising and wide spectrum of biological activities against a wide variety of diseases. In the current study, benzofuran-1,3,4-oxadiazole BF1-BF7 and benzofuran-1,2,4-triazole compounds BF8-BF15 were tested against HCV NS5B RNA-dependent RNA polymerase (RdRp) utilizing structure-based screening via a computer-aided drug design (CADD) approach. A molecular docking approach was applied to evaluate the binding potential of benzofuran-appended 1,3,4-oxadiazole and 1,2,4-triazole BF1-BF15 molecules. Benzofuran-1,3,4-oxadiazole scaffolds BF1-BF7 showed lesser binding affinities (-12.63 to -14.04 Kcal/mol) than benzofuran-1,2,4-triazole scaffolds BF8-BF15 (-14.11 to -16.09 Kcal/mol) against the HCV NS5B enzyme. Molecular docking studies revealed the excellent binding affinity scores exhibited by benzofuran-1,2,4-triazole structural motifs BF-9 (-16.09 Kcal/mol), BF-12 (-15.75 Kcal/mol), and BF-13 (-15.82 Kcal/mol), respectively, which were comparatively better than benzofuran-based HCV NS5B inhibitors' standard reference drug Nesbuvir (-15.42 Kcal/mol). A molecular dynamics simulation assay was also conducted to obtain valuable insights about the enzyme-compounds interaction profile and structural stability, which indicated the strong intermolecular energies of the BF-9+NS5B complex and the BF-12+NS5B complex as per the MM-PBSA method, while the BF-12+NS5B complex was the most stable system as per the MM-GBSA calculation. The drug-likeness and ADMET studies of all the benzofuran-1,2,4-triazole derivatives BF8-BF15 revealed that these compounds possessed good medicinal chemistry profiles in agreement with all the evaluated parameters for being drugs. The molecular docking affinity scores, MM-PBSA/MM-GBSA and MD-simulation stability analysis, drug-likeness profiling, and ADMET study assessment indicated that N-4-fluorophenyl-S-linked benzofuran-1,2,4-triazole BF-12 could be a future promising anti-HCV NS5B RdRp inhibitor therapeutic drug candidate that has a structural agreement with the Nesbuvir standard reference drug.

Zingiber officinale rhizome extracts mediated ni nanoparticles and its promising biomedical and environmental applications.

BACKGROUND: Zingiber officinale, generally known as ginger, contains bioactive phytochemicals, including gingerols and shogaols, that may function as reducing agents and stabilizers for the formation of nickel nanoparticles (Ni-NPs). Ginger extract-mediated nickel nanoparticles were synthesized using an eco-friendly method, and their antibacterial, antioxidant, antiparasitic, antidiabetic, anticancer, dye degrading, and biocompatibility properties were investigated. METHODS: UV-visible spectroscopy, fourier transform infrared spectroscopy, X-ray powder diffraction, energy-dispersive X-ray spectroscopy, and scanning electron microscopy were used to validate and characterize the synthesis of Ni-NPs. Agar well diffusion assay, alpha-amylase and glucosidase inhibitory assay, free radical scavenging assay, biocompatibility assay, and MTT assay were used to analyse the biomedical importance of Ni-NPs. RESULTS: SEM micrograph examinations revealed almost aggregates of Ni-NPs; certain particles were monodispersed and spherical, with an average grain size of 74.85 ± 2.5 nm. Ni-NPs have successfully inhibited the growth of Pseudomonas aeruginosa, Escherichia coli, and Proteus vulgaris by inducing membrane damage, as shown by the absorbance at 260 nm (A260). DPPH (2,2-diphenyl-1-picrylhydrazyl) free radicals were successfully scavenged by Ni-NPs at an inhibition rate of 69.35 ± 0.81% at 800 µg/mL. A dose-dependent cytotoxicity of Ni-NPs was observed against amastigote and promastigote forms of Leishmania tropica, with significant mortality rates of 94.23 ± 1.10 and 92.27 ± 1.20% at 1.0 mg/mL, respectively. Biocompatibility studies revealed the biosafe nature of Ni-NPs by showing RBC hemolysis up to 1.53 ± 0.81% at 400 µg/mL, which is considered safe according to the American Society for Materials and Testing (ASTM). Furthermore, Ni-NPs showed antidiabetic activity by inhibiting α-amylase and α-glucosidase enzymes at an inhibition rate of 22.70 ± 0.16% and 31.23 ± 0.64% at 200 µg/mL, respectively. Ni-NPs have shown significant cytotoxic activity by inhibiting MCF-7 cancerous cells up to 68.82 ± 1.82% at a concentration of 400 µg/mL. The IC50 for Ni-NPs was almost 190 µg/mL. Ni-NPs also degraded crystal violet dye up to 86.1% at 2 h of exposure. CONCLUSIONS: In conclusion, Zingiber officinale extract was found successful in producing stable nanoparticles. Ni-NPs have shown substantial biomedical activities, and as a result, we believe these nanoparticles have potential as a powerful therapeutic agent for use in nanomedicine.

Multifunctional Spirogyra-hyalina-Mediated Barium Oxide Nanoparticles (BaONPs): Synthesis and Applications.

This research aims to biosynthesize Barium oxide nanoparticles (BaONPs) for biomedical applications, using Spirogyra hyalina as a stabilizing and reducing agent. UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), energy-dispersive X-ray, X-ray diffraction (XRD), and scanning electron microscopy (SEM) were used to physiochemically characterize the barium oxide nanoparticles, while antibacterial, minimum inhibitory concentration, antifungal, free radicle scavenging, and anti-inflammatory assay were performed to assess the therapeutic potential of the synthesized BaONPs. Fourier transform infrared spectroscopy revealed bands at 615 and 692 cm-1 that corresponded to the formation of BaONPs. Scanning electron microscopy revealed the spherical and flower-shaped morphology of BaONPs having an average diameter of 64.01 ± 2.0 nm. Both Gram-positive and Gram-negative bacterial growth was halted by the barium nanoparticles, demonstrating their efficacy up to 19.12 ± 0.31 mm against E. coli, 18.83 ± 0.44 mm against Klebsiella pneumoniae, 17.31 ± 0.59 mm against P. aeruginosa, 16.56 ± 0.37 mm against S. aureus, and 15.75 ± 0.38 mm against S. epidermidis, respectively. The minimum inhibitory concentration was 9.0, 6.3, 5.5, 4.5, and 2.0 µg/mL for S. aureus, Klebsiella pneumoniae, S. epidermidis, P. aeruginosa, and E. coli, respectively. BaONPs were not that effective against fungal strains such as Rhizoctonia solani, Fusarium solani, and Fusarium proliferatum. The BaONPs exhibited potent anti-inflammatory and antioxidant activity through inhibiting cyclooxygenases type 1 (43.12 ± 1.21%) and 2 (41.23 ± 1.56%), and DPPH free radicles up to 43.52 ± 0.29% at 400 µg/mL. In conclusion, the biomolecules derived from Spirogyra hyalina have demonstrated remarkable ability to generate stable nanoparticles, offering promising prospects for their utilization as therapeutic agents and coating materials in various biomedical applications.

Exploring the Synthetic Chemistry of Phenyl-3-(5-aryl-2-furyl)- 2-propen-1-ones as Urease Inhibitors: Mechanistic Approach through Urease Inhibition, Molecular Docking and Structure-Activity Relationship.

Furan chalcone scaffolds belong to the most privileged and promising oxygen-containing heterocyclic class of compounds, which have a wide spectrum of therapeutic applications in the field of pharmaceutics, pharmacology, and medicinal chemistry. This research described the synthesis of a series of twelve novel and seven reported furan chalcone (conventional synthetic approach) analogues 4a-s through the application of microwave-assisted synthetic methodology and evaluated for therapeutic inhibition potential against bacterial urease enzyme. In the first step, a series of nineteen substituted 5-aryl-2-furan-2-carbaldehyde derivatives 3a-s were achieved in moderate to good yields (40-70%). These substituted 5-aryl-2-furan-2-carbaldehyde derivatives 3a-s were condensed with acetophenone via Claisen-Schmidt condensation to furnish 19 substituted furan chalcone scaffolds 4a-s in excellent yields (85-92%) in microwave-assisted synthetic approach, while in conventional methodology, these furan chalcone 4a-s were furnished in good yield (65-90%). Furan chalcone structural motifs 4a-s were characterized through elemental analysis and spectroscopic techniques. These nineteen (19)-afforded furan chalcones 4a-s were screened for urease inhibitory chemotherapeutic efficacy and most of the furan chalcones displayed promising urease inhibition activity. The most active urease inhibitors were 1-phenyl-3-[5-(2',5'-dichlorophenyl)-2-furyl]-2-propen-1-one 4h with an IC50 value of 16.13 ± 2.45 µM, and 1-phenyl- 3-[5-(2'-chlorophenyl)-2-furyl] -2-propen-1-one 4s with an IC50 value of 18.75 ± 0.85 µM in comparison with reference drug thiourea (IC50 = 21.25 ± 0.15 µM). These furan chalcone derivatives 4h and 4s are more efficient urease inhibitors than reference drug thiourea. Structure-activity relationship (SAR) revealed that the 2,5-dichloro 4h and 2-chloro 4s moiety containing furan chalcone derivatives may be considered as potential lead reagents for urease inhibition. The in silico molecular docking study results are in agreement with the experimental biological findings. The results of this study may be helpful in the future drug discovery and designing of novel efficient urease inhibitory agents from this biologically active class of furan chalcones.

Enterobacter hormaechei-Driven Novel Biosynthesis of Tin Oxide Nanoparticles and Evaluation of Their Anti-aging, Cytotoxic, and Enzyme Inhibition Potential.

Nanotechnology is a research hotspot that has gained considerable interest due to its potential inferences in the bioscience, medical, and engineering disciplines. The present study uses biomass from the Enterobacter hormaechei EAF63 strain to create bio-inspired metallic tin oxide nanoparticles (SnO2 NPs). The biosynthesized NPs were extensively analyzed using UV spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and Fourier transform infrared (FTIR) techniques. The identification of the crystalline phase was confirmed by XRD. The SEM technique elucidated the morphological characteristics and size of SnO2 NPs. SEM investigation revealed that the SnO2 NPs have a size of 10 nm with spherical morphology. The capping of NPs was confirmed by FTIR analysis that revealed the presence of different compounds found in the biomass of the E. hormaechei EAF63 strain. Later, EDX confirmed the elemental composition of NPs. Moreover, the synthesized SnO2 NPs were employed for important applications including anti-aging, anti-Alzheimer's, anti-inflammatory, anti-larvicidal, and antibacterial action against sinusitis pathogens. The highest value was observed for Streptococcus pyogenes (19.75 ± 0.46), followed by Moraxella catarrhalis (17.49 ± 0.82) and Haemophilus influenzae (15.31 ± 0.73), respectively. Among the used concentrations, the highest inhibition of 76.8 ± 0.93 for 15-lipoxygenase (15-LOX) was observed at 400 µg/mL, followed by 67.4 ± 0.91 for cyclooxygenase-1 (COX-1). So, as an outcome, E. hormaechei-mediated SnO2 NPs might be considered as the safe and effective nanoplatforms for multifunctional biological applications in the field of nanomedicine.

Exploring the antibacterial, antidiabetic, and anticancer potential of Mentha arvensis extract through in-silico and in-vitro analysis.

BACKGROUND: Mentha arvensis has been utilized in diverse traditional medicines as an antidiabetic, anticarcinogenic, antiallergic, antifungal, and antibacterial agent. In this work, we have explored the phytochemical analyses and pharmacological potential of Mentha arvensis using both in silico and in vitro approaches for drug discovery. METHODS: To determine the extract with the highest potential for powerful bioactivity, ethanol was used as the solvent. The phytochemical components of the extracts were quantified using liquid chromatography-mass spectrometry analysis. The potential bioactivities of extracts and lead phytocompounds, including their antibacterial, cytotoxic, and anti-diabetic effects, were evaluated. RESULTS: The compounds oleanolic acid, rosmarinic acid, luteolin, isoorientin, and ursolic acid have been identified through liquid chromatography mass spectrometry analysis. Based on antimicrobial research, it has been found that the Mentha arvensis extract shows potential activity against K. pneumoniae which was 13.39 ± 0.16. Mentha arvensis has demonstrated a greater degree of efficacy in inhibiting α-glucosidase, with an inhibition rate of 58.36 ± 0.12, and in inhibiting α-amylase, with an inhibition rate of 42.18 ± 0.83. The growth of HepG2 cells was observed to be significantly suppressed upon treatment with extracts obtained from Mentha arvensis. Finally, In-silico methods demonstrated that the Luteolin and Rosmarinic acid exhibit acceptable drug-like characteristics. Furthermore, Molecular docking studies further demonstrated that both compounds have strong potential to inhibit the active sites of therapeutically relevant enzymes involved in Diabetes, Bacterial infections, and Cancer. CONCLUSIONS: The results of this study suggest that the Mentha arvensis extract possesses potent pharmacological potentials, particularly in terms of antibacterial, anti-diabetic, and cytotoxic effects. Particularly, Luteolin and Rosmarinic acid were identified as the top contenders for potential bioactivity with acceptable drug-like properties.

Experimental study on the dissipation performance of supersaturated total dissolved gas in microbubble treatment.

The production of total dissolved gas (TDG) supersaturation resulting from dam discharges has been identified as a causative factor for gas bubble disease (GBD) or mass mortality in fish. In this study, the mitigation solution for fish refuge in supersaturated TDG water was explored by using microbubbles generated by aeration to enhance supersaturated TDG dissipation. The effects of various aeration factors (aeration intensity, water depth, and aerator size) on the dissipation processes of supersaturated TDG were quantitatively investigated through a series of tests conducted in a static aeration column. The results indicated that the dissipation rates of supersaturated TDG increased as a power function with the factors of aeration intensity and aerator size and decreased as a power function with increasing water depth. A universal prediction model for the dissipation rate of supersaturated TDG in the aeration system was developed based on the dimensional analysis of the comprehensive elements, and the parameters in the model were determined using experimental data. The outcomes of this study can furnish an important theoretical foundation and scientific guidance for the utilization of aeration as a measure to alleviate the adverse impacts of supersaturated TDG on fish.

The preparation of Diacylglycerol-rich soybean oil by acetylated modification of arachin nanoparticles for W/O Pickering emulsion system.

Pickering emulsion catalytic system (PEC) stabilized by nanoparticles is an efficient catalytic platform. Herein, a high-performance PEC was constructed by acetylated modification of arachin nanoparticles (AAPs). The results showed the pI of arachin was decreased from pH 5.5 to pH 3.5. The surface hydrophobicity index was significantly increased (from 56.28 ± 4.23 to 120.77 ± 0.79) after acetylated modification. The three-phase contact angle of AAPs was 91.20 ± 0.98°. AAPs were used as lipase immobilization carriers to increase the activity of free lipase fabricating lipase-AAPs. The immobilization efficiency and activity of lipase-AAPs were 12.95 ± 0.03% and 1.74 ± 0.07 U/mg, respectively. Enzymatic reaction kinetics showed that Vm of lipase-AAPs was twice of free lipase. Km was 1/5 of free lipase. The catalytic efficiency of PEC to prepare DAG was 2.36 times of biphasic catalytic system (BCS). This work provided a promising way to promote the efficiency of DAG preparation.

Prevalence and Predictors of Excessive Polypharmacy in Geriatric Inpatients: A Retrospective Cross-Sectional Study in Indonesia.

OBJECTIVES: To investigate the prevalence and predictors of excessive polypharmacy in geriatric inpatients in Indonesia. METHODS: This retrospective cross-sectional study included 1533 inpatients over the age of 60 years at Universitas Airlangga Hospital, Indonesia. Effects of a patient's baseline characteristics on excessive polypharmacy were evaluated using logistic regression analysis. RESULTS: Excessive polypharmacy was observed in 133 (8.67%) patients. Ulcer (OR 8.151,95% CI 2.234-29.747, P = .001), cancer (OR 5.551, 95% CI 1.602-19.237, P = .007), and renal diseases (OR 3.710, 95% CI 1.965-7.006, P < .001) were the 3 strongest predictors of excessive polypharmacy. An association between hospital stay of more than 3 days and excessive polypharmacy was identified (OR 2.382, 95% CI 1.109-5.115, P = .026). DISCUSSION: One in 12 elderly Indonesians was found to practice excessive polypharmacy. Several chronic conditions and increased length of hospital stay were the factors associated with excessive polypharmacy.

In Silico Development of Novel Benzofuran-1,3,4-Oxadiazoles as Lead Inhibitors of M. tuberculosis Polyketide Synthase 13.

Benzofuran and 1,3,4-oxadiazole are privileged and versatile heterocyclic pharmacophores which display a broad spectrum of biological and pharmacological therapeutic potential against a wide variety of diseases. This article reports in silico CADD (computer-aided drug design) and molecular hybridization approaches for the evaluation of the chemotherapeutic efficacy of 16 S-linked N-phenyl acetamide moiety containing benzofuran-1,3,4-oxadiazole scaffolds BF1-BF16. This virtual screening was carried out to discover and assess the chemotherapeutic efficacy of BF1-BF16 structural motifs as Mycobacterium tuberculosis polyketide synthase 13 (Mtb Pks13) enzyme inhibitors. The CADD study results revealed that the benzofuran clubbed oxadiazole derivatives BF3, BF4, and BF8 showed excellent and remarkably significant binding energies against the Mtb Pks13 enzyme comparable with the standard benzofuran-based TAM-16 inhibitor. The best binding affinity scores were displayed by 1,3,4-oxadiazoles-based benzofuran scaffolds BF3 (-14.23 kcal/mol), BF4 (-14.82 kcal/mol), and BF8 (-14.11 kcal/mol), in comparison to the binding affinity score of the standard reference TAM-16 drug (-14.61 kcal/mol). 2,5-Dimethoxy moiety-based bromobenzofuran-oxadiazole derivative BF4 demonstrated the highest binding affinity score amongst the screened compounds, and was higher than the reference Pks13 inhibitor TAM-16 drug. The bindings of these three leads BF3, BF4, and BF8 were further confirmed by the MM-PBSA investigations in which they also exhibited strong bindings with the Pks13 of Mtb. Moreover, the stability analysis of these benzofuran-1,3,4-oxadiazoles in the active sites of the Pks13 enzyme was achieved through molecular dynamic (MD) simulations at 250 ns virtual simulation time, which indicated that these three in silico predicted bio-potent benzofuran tethered oxadiazole molecules BF3, BF4, and BF8 demonstrated stability with the active site of the Pks13 enzyme.