Current Issue : October-December Volume : 2026 Issue Number : 4 Articles : 5 Articles
A novel lanthanum(III) salicylate complex (La(Sa)3) with potential biomedical applications was chemically synthesized via the reaction of salicylic acid (SA) with lanthanum oxide nanoparticles (La2O3NPs). This two-step synthesis approach involved the initial preparation of La2O3NPs followed by their coordination with mixed SA ligands, after which the resulting complex and its precursors were comprehensively characterized. The structure of the La(Sa)3 complex was investigated using nuclear magnetic resonance (NMR) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, field-emission scanning electron microscopy (FE-SEM), and transmission electron microscopy (TEM). Molecular docking studies of the newly synthesized complex were conducted to elucidate the interactions between La(Sa)3 and the target microbial protein at the molecular level. Comparative evaluations of the bacteriostatic and bactericidal activities of the La(Sa)3 complex, its ligand (SA), and La2O3NPs were performed against Gram-positive and Gramnegative bacteria. These studies demonstrated that the La(Sa)3 complex exhibited significant antibacterial activity against the selected bacterial strains. The results further indicated that La(Sa)3 showed enhanced antibacterial properties due to a synergistic effect with La2O3NPs. The morphology of the La(Sa)3 complex revealed that the chemical synthesis of the La(Sa)3 complex in the presence of La2O3NPs resulted in notable differences in powder and particle morphology. Spectral analyses confirmed that the synthesized La2O3NPs successfully reacted with SA to form La(Sa)3 complex molecules. The data obtained from the in silico studies were consistent with the results of the experimentally conducted antibacterial assays. The experimental study results suggest that the La(Sa)3 complex may be developed as a promising antibacterial drug candidate....
Succinimide derivatives are an essential class of compounds with diverse pharmacological applications. Different derivatives of succinimide as Schiff’s base were designed for good inhibitory activity against the human GABAA receptor. Compounds that inhibit GABAA are effective as anti-epileptic agents. Virtual screening methods, such as chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, play key roles in drug discovery and development, and molecular docking was used. ADMET properties and drug likeliness of all investigated compounds were predicted by Swiss ADMET software. A higher binding affinity and interactions have been observed with the designed compounds compared to the standard compounds (phenobarbital and flumazenil)....
The sirtuin 1 (SIRT1) enzyme plays a pivotal role in regulating cellular homeostasis, making it a high-priority target for treating abolic and age-related diseases. We report the synthesis and biological evaluation of a novel series of 1,5-benzodiazepine derivatives designed as potential SIRT1 activators. High-throughput screening using recombinant SIRT1 protein in a luminescent assay was employed, identifying 2,4-disubstituted 2,3-dihydro-1H-1,5-benzodiazepines as superior activators, whereas coumarin chalcones inhibit SIRT1 activity. Using molecular docking against hSIRT1, we found that the activators fit perfectly within a hydrophobic pocket of the allosteric site, being anchored by a conventional hydrogen bond to Asn226 and stabilized by -alkyl interactions with Ile227. Beyond these structural studies, we evaluated the antidiabetic potential of one of the derivatives, known as pyrabentin. The effectiveness of pyrabentin under 8-week oral administration at 100 mg/kg per os in reducing glucose intolerance, insulin resistance, and obesity in animals with the metabolic memory model at the level of action of the comparator drug metformin has been proven. Finally, our findings demonstrate that the heterocyclic substitutions of the 1,5- benzodiazepine moiety are critical determinants of their interaction with the STAC-binding domain, providing a structure-based rationale for more efficient SIRT1 activators for the treatment of type 2 diabetes....
Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by the accumulation of the toxic protein amyloid-β, formation of tau-containing neurofibrillary tangles, neuroinflammation, and synaptic dysfunction, highlighting the need for new therapeutic strategies capable of modulating multiple pathological pathways simultaneously. In this study, a structure-based in silico approach was applied to evaluate the multi-target potential of two previously reported pyrrole-based compounds (pyrrole 1 and pyrrole 2) with known monoamine oxidase-B (MAO-B) inhibitory activity and low neurotoxicity. Molecular docking studies were performed against a panel of key AD-related targets, including GSK-3β, APP, MAO-B, BACE1, AChE, BChE, COX-2, GABA-B receptor, NMDA receptor, and E3 ubiquitin ligase CHIP, using Glide XP docking. The results revealed that compound pyrrole 1 may have favorable predicted binding affinities across several targets, with relatively strong docking scores for GSK-3β and COX-2. The binding mode analysis indicated that pyrrole 1 adopts poses consistent with interaction patterns commonly observed for ATP-competitive GSK-3β inhibitors and COX-2 ligands. In silico ADMET profiling using the software SwissADME and ProTox 3.0 indicated distinct pharmacokinetic and safety profiles for the two compounds, with pyrrole 2 showing superior drug-likeness and predicted blood–brain barrier penetration, while pyrrole 1 displayed a more favorable overall toxicity profile. Collectively, these findings identify pyrrole 1 as a theoretically promising multi-target candidate for AD requiring experimental validation, while providing a strong structural basis for further optimizations and subsequent experimental confirmation....
Introduction: 3-Alkynyl-6-aryl-isothiazolo[4,3-b]pyridines have previously been shown to be potent inhibitors of the lipid kinase FYVE finger-containing phosphoinositide kinase (PIKfyve), displaying broad-spectrum antiviral activity. Methods: To further study their structure–activity relationship (SAR), an efficient synthesis toward 3- bromo-5-chloro-isothiazolo[4,3-b]pyridine was established. It allowed to introduce structural modifications at positions 3 and 5 by palladiumcatalyzed cross-coupling reactions and nucleophilic aromatic substitutions. Results and discussion: It led to the generation of a focused library of 3,5- disubstituted isothiazolo[4,3-b]pyridines. Several derivatives exhibited potent PIKfyve inhibition (in the low nM range) in a biochemical assay and antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (in the low μM range). To gain an insight in their binding mode, molecular modeling was applied, indicating that these 3,5- disubstituted isothiazolo[4,3-b]pyridines bind to the ATP-binding site of PIKfyve, although with a different binding mode from that of the 3,6- disubstituted isothiazolo[4,3-b]pyridines....
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