Introduction: Aminothiazole is an important moiety exhibiting various biological properties, including antioxidant, bacteriostatic, antibiotic, anticonvulsant, anti-HIV, cytotoxic, antifungal, anti-inflammatory and neuroprotective activities. Materials and Methods: Here, we aimed to synthesise aminothiazole derivatives bearing an oxadiazole moiety and determine their inhibitory activity against the Acetylcholinesterase (AChE) enzyme. The antioxidant activity of all molecules was evaluated using the DPPH radical scavenging method. Results: Among all derivatives, compound 3b emerged as a potential candidate, exhibiting AChE inhibitory and antioxidant activity with IC₅₀ values of 3.55 μM and 2.17 μM, respectively. Discussion: In the molecular docking analysis, the best docking score was observed for the most active compound, 3b, which also showed strong in-vitro inhibition. Conclusion: The synthesised compound (3b) can be considered a potential lead for the further development of new compounds against Alzheimer’s disease.

Introduction: Overactive bladder (OAB) is a common disorder characterized by urine urgency, frequency, and incontinence, which has a substantial impact on quality of life. Current treatments, such as antimuscarinics and beta-3 agonists, frequently have limitations, including side effects and varying efficacy. Fesoterodine fumarate, a muscarinic receptor antagonist, has emerged as a treatment option; however, comprehensive analyses of its mechanisms, clinical efficacy, and potential alternatives are required. Methods: A thorough literature search was carried out using PubMed, Scopus, and Web of Science databases. The keywords used included "overactive bladder", "fesoterodine", "ion channels", and "pharmacological interventions". Studies were chosen based on their relevance, sample size, and methodological rigor. Data were combined to assess efficacy and safety and establish the patterns. Results: In clinical studies, fesoterodine has revealed considerable effectiveness in lowering OAB symptoms while maintaining a safety profile comparable to other anti-muscarinics. In preclinical investigations, novel medicines, such as TRP channel modulators (e.g., nifedipine) and enzymetargeting medications (e.g., PDE5 inhibitors), have shown promise. The drawbacks have been found to include diverse study designs and the underrepresentation of varied communities. Discussion: The present research study focused on pharmacological treatments for OAB, focusing on fesoterodine's mechanism of action, clinical trials, and novel medications targeting ion channels, enzymes, and the autonomic nervous system. Conclusion: The frequency and amount of urination are associated with the disease condition, stool movement, and emptying. Pathophysiological changes associated with the increased sensitivity in the gut, inflammatory response, and microbiota in the intestine largely affect the OAB.

Introduction: Caftaric acid (CFA), a natural product, has been experimentally proven to have diverse pharmacological properties. The nexus of NF-kB/VEGF/MMP9 signaling is believed to be associated with angiogenesis and vascular complications in patients with diabetic retinopathy (DR). The aim and objectives of the study are to explore the therapeutic relevance of CFA in DR, particularly focusing on pathological angiogenesis mechanisms involving the NF-κB / VEGF / MMP-9 signaling pathway associated with DR. To assess the anti-angiogenic potential of CFA using the CAM (Chorioallantoic Membrane) and cell culture-based models. Methods: The cytotoxicity screening of CFA was performed using Human Retinal Pericyte cells (HRPCs). In vitro free radical (DPPH, OH, NO) assays were performed for CFA and standard ascorbic acid. An in vitro CAM assay of CFA and standard bevacizumab (15 μg/mL) was performed to assess angiogenesis in the CAM. In vivo STZ assay for CFA (100 and 200 mg/kg; oral) and standard epalrestat (150mg/kg/day; oral) were performed to observe the intensity of DR by using male Wistar albino rats. After the last dose of test and standard drug administration, all animals were sacrificed to carry out biochemical, western blotting, and histopathological analysis. Results: The CFA showed concentration-dependent scavenging activity of DPPH, NO, and OH radicals comparable to that of the standard ascorbic acid. Significant antiangiogenic effects were observed for CFA (100 and 250 μg/mL), with scores of 1 and 1.6, respectively. CFA (200μg/mL; CAM model) and CFA (200 mg/kg; STZ model) significantly reduce VEGF, MMP9, and NF-κB expressions. Discussion: VEGF and MMP9 are major drivers of angiogenesis and vascular permeability, and their inhibition by CFA suggests a reduction in retinal angiogenesis and vascular leakage. Its mechanism involves modulation of the NFκB/VEGF/MMP-9 signaling pathway, leading to reduced pathological angiogenesis in both in vitro and in vivo models. This reinforces the CFA's potential in mitigating the pathological features of DR. Conclusion: CFA demonstrates significant anti-angiogenic and anti-inflammatory potential by suppressing MMP-9 activity and expression. These findings suggest that CFA could serve as a promising therapeutic candidate for managing diabetic retinopathy by targeting abnormal angiogenesis and inflammation. other: Nil

Introduction: Phytase enzyme catalyzes the hydrolysis of phytate, an anti-nutrient compound present in cereals and grains, to release orthophosphate and myo-inositol hexakisphosphate with lower degrees of phosphorylation, with metal ions, proteins, and starch chelated to phytate naturally. The study aimed to screen potential phytase-producing bacterial isolates and characterize the extracellular phytase of the bacterial isolate with the best phytase activity. Methods: A promising isolate (R5-C2-C4) out of thirty tested bacterial strains, which showed the best hydrolysis efficiency on Phytase Selective Medium (PSM) plates, was selected to investigate phytase production in Liquid Phytase Selective Medium (LPSM) under constant conditions of 37°C and pH 7.0 during a 72-hour incubation period, with measurements taken at 24-hour intervals using phytase production activity assay. Results: The local isolate Bacillus subtilis (C4) was found to produce significantly the highest phytase activity of 0.818 Unit/ml out of the tested isolates during 72 h of incubation at 37°C with the pH of 7.0 as a characterization of crude phytase. Discussion: Enzyme activity and stability under varying pH and temperature conditions are always a significant challenge during food and feed processing. Most studies indicate that bacterial phytase and especially Bacillus sp. phytase had a pH optimum of (6.5-7.5), and optimum temperature of (35-60)°C, where the phytase parameters of this study isolate, Bacillus subtilis found to be in the same range. Conclusion: The local isolated Bacillus subtilis produces its significant amount of phytase with ideal production parameters, which would considerably make it useful for applications in feed and food.

Introduction: Tuberculosis is a life-threatening infectious disease and a major public health concern. The recent emergence of extensively and totally resistant strains of Mycobacterium tuberculosis has driven the search for new antituberculosis agents with previously unexploited mechanisms of action. The main aim of this study is to develop inhibitors with dual-targeted activity toward M. tuberculosis leucyl-tRNA synthetase (LeuRS) and methionyl-tRNA synthetase (MetRS). Methods: In order to find M. tuberculosis LeuRS and MetRS inhibitors, virtual screening was performed with AutoDock software. The top-scoring compounds were then evaluated in vitro in aminoacylation assay using radioactive [14C]-L-leucine. Results: The low molecular weight inhibitors targeting M. tuberculosis LeuRS were identified among Benzo[b]oxepine-4-carboxylic acid (5-benzyl-thiazol-2-yl)-amide derivatives. Discussion: The most active compound – 7-Methoxy-benzo[b]oxepine-4-carboxylic acid [5-(2- fluoro-benzyl)-thiazol-2-yl]-amide, inhibited mycobacterial LeuRS with IC50 value of 19.7 μM. It was found that this compound inhibits M. tuberculosis MetRS by 96.5% at the concentration of 100 μM. Based on molecular docking results, the compounds from this class bind simultaneously to adenine recognition region and amino acid acceptor region of M. tuberculosis aminoacyl-tRNA synthetases synthetic sites. Conclusion: Benzo[b]oxepine-4-carboxylic acid (5-benzyl-thiazol-2-yl)-amide derivatives can be the basis for chemical optimization and biological investigations.

Introduction: Antimicrobial resistance (AMR) is a growing global health challenge that poses a significant threat to public health, healthcare systems, and socioeconomic stability. The misuse and overuse of antibiotics, along with environmental factors, have accelerated the development of resistance in key antibiotic classes, including penicillins, Aminoglycosides, Macrolides, and Tetracyclines. Despite advancements in antibiotic discovery, the rise of resistant microorganisms continues to jeopardize the efficacy of life-saving treatments. This study aims to provide a comprehensive analysis of AMR, focusing on its sources, mechanisms, and impacts. Specific objectives include exploring the historical supremacy of antibiotics, reviewing 10 FDA-approved antibiotics from 2020–2024 with 23 combination therapy drugs, investigating chemical strategies against AMR, and proposing solutions to combat resistance, particularly in widely used antibiotic classes. The paper also aims to highlight the environmental influence on AMR and suggest sustainable approaches to mitigate its spread. Methods: The study involved a detailed review of scientific literature, regulatory reports, and case studies related to AMR. Key areas analyzed include mechanisms of resistance development, chemical modifications of antibiotics, combination therapies, and environmental factors influencing AMR. Data on recently approved antibiotics (2020–2024) by the FDA were examined to assess progress in antibiotic development. Additionally, targeted strategies to overcome resistance in Penicillins, Aminoglycosides, Macrolides, and Tetracyclines were critically reviewed. Results: Recent FDA-approved antibiotics (2020–2024) and key drug combinations have shown progress against resistant pathogens, particularly in major antibiotic classes. However, persistent misuse, environmental factors, and limited innovation continue to drive antimicrobial resistance globally. The most important and widely used chemical combinations of drugs, including Penicillin, Tetracycline, Macrolides, and Aminoglycosides, have been highlighted in this review. Discussion: Antimicrobial resistance (AMR) is a global threat to public health, healthcare systems, and socioeconomic stability, particularly in India. Advanced therapies, chemical modifications, and CRISPR-Cas9-based approaches are being explored to counteract resistance. The environmental aspect of AMR, including wastewater, soil, and pharmaceutical pollution, is also crucial. Comprehensive monitoring and stewardship programs, interdisciplinary collaboration, and evidence-based guidelines are essential for reducing the global AMR burden. Conclusion: A multifaceted strategy combining chemical innovation, responsible use, and environmental control is essential to combat AMR. Urgent global collaboration is needed to preserve antibiotic effectiveness for future generations.

Background: Heterocyclic compounds containing oxygen, nitrogen, and/or sulfur atoms are of significant importance in drug discovery and development. Pyrazole moieties, in particular, have broad applications across various fields, including herbicides, corrosion inhibitors, electron transport materials, polymers, and luminescent materials. This underscores the growing need in medicinal chemistry to design new anticancer agents that improve therapeutic efficacy and safety. Methods: A series of novel pyrazole-naphthalene derivatives were synthesized from chalcones, which were obtained through an aldol condensation between benzaldehyde and acetophenone, followed by a Claisen-condensation reaction. All the synthesized compounds were characterized by NMR and IR spectrum examinations, as well as C, H, and N analyses. The synthesized compounds were screened for biological activity against the breast cancer cell line (MCF-7 strain) using an MTT assay. Furthermore, a molecular docking study was performed to elucidate the binding modes of synthesized ligands in the active pockets of the three-dimensional crystallographic structure of CDK2 in complex with inhibitor RC-1-148 (PDB ID: 3QTR) for further predicting the mechanism of action. Results: Molecules R5, R8, and R9 were found to be the most active compounds in the series, exhibiting sensitivity of up to 5.0 μg/ml. Additionally, compounds R8, R13, and R10 demonstrated activity against cancer cells, with sensitivity reaching up to 3.2 μg/ml. Conclusion: The current study highlights the unique structural characteristics and significant biological activity of the synthesized compounds. In the pursuit of novel anticancer molecules, these compounds could prove beneficial to society.

Introduction: Benzodiazepines are used for their anxiolytic, antiepileptic, muscle relaxant and hypnotic effects. In vitro, diazepam is predominantly metabolized to temazepam and nordiazepam (N-desmethyldiazepam). Since acetylcholinesterase is involved in the metabolism of diazepam, inhibition of the enzyme activity may have a significant effect on the therapeutic effect of the drug. To determine the inhibitory effect of 2,2,4-trimethyl-2,3-dihydro-1H-benzo[b][1,4]diazepine on acetylcholinesterase enzyme activity by conducting a comprehensive analysis that includes: measuring the enzyme activity in the presence of various concentrations of the inhibitor, determining the type of inhibition through kinetic studies, and assessing the potential therapeutic applications of the inhibitor in conditions associated with acetylcholinesterase dysfunction. Methods: In this study, the inhibitory properties of 2,2,4-trimethyl-2,3-dihydro-1-Hbenzo[ b][1,4]diazepine on the activity of the enzyme acetylcholinesterase were tested spectrophotometrically at three different temperatures of 25?, 30?, and 37?. The substance was synthesized by a condensation reaction between o-phenyldiamine and acetone in the presence of phosphorus oxychloride on solid support (MgO). The solid product was obtained by crystallization from n-hexane. Each tested sample contained an appropriate concentration of the substrate acetylcholine iodide (AChI) in the range from 1.00 to 4.00 mmol·L-1; 5,5-dithiobis(2-nitrobenzoic acid) (DTNB) concentration 3 mmolL-1, phosphate buffer (KH2PO4/K2HPO4) pH value 8, tested substance concentration (17.70, 35.40, 53.10 mmol·L-1), and acetylcholinesterase solution (AChE) activity 0.54 UmL-1. Results: Using the spectrophotometric method, it was concluded that the examined diazepine shows a competitive type of inhibition on the enzyme acetylcholinesterase. 30°C was determined to be the optimal assay temperature. The highest inhibition was observed at 25°C using 53.10 mmol·L?¹ of the inhibitor. As the temperature increases, the inhibition decreases. Discussion: Based on the Lineweaver-Burk diagram, we gain insight into the type of inhibition exhibited by the synthesized compound. The intercept on the ordinate remains unchanged; the slope of the line increases, and the intercept on the abscissa decreases, indicating that it is a competitive inhibition. Conclusion: Considering the results obtained by spectrophotometric analysis, it was concluded that the enzyme acetylcholinesterase follows the Michaelis-Menten model. It has been proven that the synthesized compound exhibits inhibitory properties on the activity of acetylcholinesterase.

Introduction: Penicillin G amidase is an industrially significant enzyme widely employed in the production of semi-synthetic β-lactam antibiotics through the hydrolysis of Penicillin G to 6- aminopenicillanic acid. Owing to its commercial importance, extensive research has focused on improving the operational stability, reusability, and catalytic efficiency of PGA through various immobilization strategies. Methods: Optimization of multiple parameters for free and immobilized Penicillin G Acylase (PGA) is critical for improving the enzyme';s catalytic effectiveness, stability, and reusability in industrial and medicinal applications. This procedure entails methodically altering and analyzing variables such as substrate concentration, mechanical stability, cycle number, and storage conditions, and their effects on operational stability, pH, and temperature. PGA was optimized by entrapment on collagen hydrogel beads, resulting in collagen hydrogel + gelatin hybrid gel beads. Result: Immobilized PGA in Collagen Hydrogel + gelatin hybrid beads showed superior thermal stability, reusability, and storage stability as compared to gelatin-immobilized PGA. The entrapment of PGA onto Collagen Hydrogel + gelatin hybrid beads revealed several advantages and could be used in the production of 6-aminopenicillanic acid (6APA). Discussion: The study investigated the biochemical behavior of Penicillin G amidase (PGA) immobilized on collagen hydrogel and a collagen–gelatin bio-composite. Relative analysis focused on enzyme activity, stability, and mechanical strength, revealing insights into their appropriateness as immobilization matrices for enhanced PGA performance in industrial biocatalysis applications. Conclusion: Hydrogel + gelatin hybrid beads are more beneficial in industrial applications due to their greater stability and usability. PGA entrapment onto Hydrogel + gelatin hybrid beads has shown numerous advantages and may be useful in the manufacture of 6APA (6-aminopenicillanic acid).