Journal of Pharmaceutical Research International

Design, Synthesis and Biological Evaluation and Molecular Docking Study of (Z)-7-Nitro-1-Phenyl-3-((2-((1-Phenylethylidene) Amino) Ethyl) Amino) Quinoxalin-2(1H)-One Derivatives

2026-09-02T11:50:05+00:00

Aims: To synthesize (Z)-7-nitro-1-phenyl-3-((2-((1-phenylethylidene)amino)ethyl)amino)quinoxalin-2(1H)-one derivatives and evaluate their possible biological properties.

Methods: The substituted (Z)-7-nitro-1-phenyl-3-((2-((1-phenylethylidene)amino)ethyl)amino)quinoxalin-2(1H)-one derivatives were synthesized by reacting 3-((2-aminoethyl)amino)-7-nitro-1-phenylquinoxalin-2(1H)-one with different substituted aromatic ketones. The synthesized compounds were characterized using nuclear magnetic resonance (NMR) spectroscopy. Their acetylcholinesterase and butyrylcholinesterase inhibitory activities were evaluated spectrophotometrically based on the enzymatic hydrolysis of acetylthiocholine iodide and butyrylcholine chloride. Molecular docking was performed for compounds 1(a-g) against the three-dimensional structure of recombinant human acetylcholinesterase (PDB ID: 4EY7).

Results: Compounds 1e (IC₅₀ = 0.04 ± 0.01 µM) and 1f (IC₅₀ = 0.75 ± 0.06 µM) were the most active acetylcholinesterase inhibitors, while compounds 1b (IC₅₀ = 0.06 ± 0.02 µM) and 1f (IC₅₀ = 0.84 ± 0.02 µM) showed the strongest butyrylcholinesterase inhibition among the reported compounds. The docking results revealed several interactions between ligands 1(a-g) and the protein binding pocket, highlighting the roles of specific amino acid residues and interaction types in stabilising the complexes. Each ligand displayed a distinct interaction profile contributing to its predicted binding affinity and specificity.

Conclusion: The acetylcholinesterase and butyrylcholinesterase inhibitory activities of the synthesized compounds, together with their docking profiles, support further investigation of this derivative series as potential cholinesterase inhibitors.

In vitro Antioxidant and Antimicrobial Activities of Euphorbia thymifolia Extracts and Development of an Experimental Oral Rinse

2026-09-02T11:57:44+00:00

Aims: Oral diseases are associated with complex microbial biofilms and oxidative inflammatory processes. This study evaluated the phytochemical profile, total phenolic content, DPPH radical-scavenging activity, and preliminary antimicrobial activity of aqueous and hydroethanolic extracts of Euphorbia thymifolia and examined the activity and quality attributes of experimental oral-rinse formulations.

Methodology: Aqueous and hydroethanolic extracts were subjected to qualitative phytochemical screening and determination of total phenolic content. Antioxidant activity was assessed by the DPPH assay. Agar well diffusion was used as a preliminary screening method against Streptococcus mitis, Streptococcus salivarius, Streptococcus mutans, Staphylococcus aureus, Escherichia coli, and Candida albicans. Experimental oral-rinse formulations were evaluated for inhibition-zone diameter, pH, density, and microbiological quality.

Results: Polyphenols, flavonoids, tannins, alkaloids, and saponins were detected in all extracts. The aqueous extract had an IC50 of 19.3 ± 2.1 µg/mL, followed by the 60:40 hydroethanolic extract at 21.5 ± 1.8 µg/mL. Extract inhibition zones ranged from 18.1 ± 0.2 to 23.4 ± 0.4 mm. Among extract-containing formulations, inhibition zones ranged from 12.8 ± 0.3 to 18.4 ± 0.4 mm. The formulations had a mean pH of 7.28 ± 0.02 and a mean density of 1.035 ± 0.01 g/mL. The total aerobic mesophilic count was 2.2 × 10³ CFU/g and exceeded the limit applied in the study, although the specified coliforms, yeasts and moulds, Escherichia coli, and Staphylococcus aureus were not detected.

Conclusion: Euphorbia thymifolia extracts demonstrated DPPH radical-scavenging and preliminary agar-diffusion activity under the conditions tested, and measurable activity remained after incorporation into experimental oral-rinse formulations. These findings support further chemical standardisation and quantitative antimicrobial investigation; however, the current results do not establish clinical efficacy, product stability, or oral safety. Optimisation of preservation and additional cytotoxicity, stability, biofilm, and in vivo studies are required.

AI-Assisted Stability-Indicating RP - HPLC Method Development and Validation for the Quantitative Estimation of Tafamidis in Bulk Drug and Pharmaceutical Dosage Forms

2026-09-04T10:53:20+00:00

A stability-indicating reverse-phase high-performance liquid chromatographic (RP-HPLC) method was developed and validated for the quantitative estimation of Tafamidis in bulk drug and pharmaceutical dosage forms. Chromatographic separation was achieved using a Phenomenex Gemini ODS C18 column (250 × 4.6 mm, 5 µm) with methanol and phosphate buffer (25:75, v/v) as the mobile phase at a flow rate of 1.0 mL/min. Detection was performed at 312 nm using a PDA detector. The method was evaluated for system suitability, specificity, linearity, accuracy, precision, intermediate precision, robustness, limit of detection, limit of quantification, and stability-indicating capability. Tafamidis showed a mean retention time of approximately 3.16 min and linear response over the concentration range of 10–50 µg/mL, with a correlation coefficient of 0.999. The assay of the pharmaceutical dosage form was 99.23%. Recovery at the evaluated concentration levels was approximately 100.41–100.44%, while method precision and intermediate precision showed low percentage relative standard deviations. The calculated LOD and LOQ were 0.597 and 1.811 µg/mL, respectively. Forced-degradation studies under acidic, alkaline, oxidative, thermal, photolytic, and hydrolytic conditions demonstrated separation of Tafamidis from degradation products. The experimental dataset also provides a basis for future evaluation of artificial intelligence and machine-learning approaches for chromatographic optimisation; however, such models were not used to generate the reported validation results.

Repurposing FDA-Approved Drugs and Exploring Nutraceuticals for Diabetes Management via Molecular Docking and ADMET Analysis

2026-09-08T13:28:51+00:00

Diabetes mellitus is a chronic metabolic disorder characterised by persistent hyperglycaemia and complications that may affect multiple organ systems. This study used a computational approach to compare selected nutraceutical compounds with FDA-approved antidiabetic drugs for their potential interactions with diabetes-related protein targets. Twenty compounds, comprising ten nutraceutical molecules and ten approved antidiabetic drugs, were evaluated by molecular docking against two target proteins, 3A4A and 2PRG. Docking simulations were conducted using AutoDock 4.2, and the resulting binding affinities and amino acid interactions were assessed. The predicted pharmacokinetic and toxicity characteristics were further examined through in silico ADMET analysis, including drug-likeness, gastrointestinal absorption, blood-brain barrier permeability, P-glycoprotein substrate prediction, and toxicity parameters. Among the nutraceutical compounds, glycyrrhetinic acid showed the strongest interaction with 3A4A, with a docking score of −7.12 kcal/mol, while berberine demonstrated a docking score of −6.34 kcal/mol. For 2PRG, glycyrrhetinic acid and berberine also showed favourable interactions, with docking scores of −7.55 kcal/mol and −7.20 kcal/mol, respectively. The approved drugs metformin and linagliptin also exhibited strong binding profiles, supporting the comparative docking approach used in this study. The ADMET results indicated that several nutraceutical compounds had acceptable predicted pharmacokinetic features and toxicity profiles comparable to those of selected conventional drugs. Overall, the findings suggest that glycyrrhetinic acid, berberine, metformin, and linagliptin may warrant further experimental evaluation as candidates or reference compounds in diabetes-related drug discovery. These computational results should be interpreted as preliminary and require biological validation before therapeutic relevance can be confirmed in future diabetes research and practice.