Tuberculosis (TB) remains a significant global health burden, necessitating the discovery of new therapeutic strategies. In this study, we targeted phenyloxazoline synthase MbtB, a crucial enzyme in the iron acquisition pathway of Mycobacterium tuberculosis, which is vital for bacterial survival under iron-limited conditions. Recognizing MbtB as a promising drug target, we aimed to identify potential inhibitors from a curated library of FDA-approved drugs available in the ZINC database.

To simulate the enzyme’s binding environment, multiple conformations of the substrate’s transition state were used as query models. Conformational ensembles of both the query structures and library compounds were generated using Balloon (v1.8.2). Virtual screening was performed using ShaEP (v1.4.0), which compares molecules based on shape and electrostatic potential similarities. This approach led to the identification of several promising candidates that closely mimic the transition state structure of the MbtB substrate.

The top five hits from the screening were subjected to molecular dynamics simulations to evaluate their binding stability and interactions with the target protein at the atomic level. These leading compounds will be procured and tested for anti-TB activity under both iron-rich and iron-depleted conditions, in accordance with previously established methodologies. This study presents a structure-based strategy for repurposing FDA-approved drugs to target iron metabolism in M. tuberculosis.

The valorization of olive oil production residues represents an innovative and sustainable strategy aligned with circular economy principles and the United Nations Sustainable Development Goals. In this study, we aimed to explore the phytochemical composition and neuroprotective potential of organic extracts obtained from olive pomace of the Arbequina and Arbosana cultivars. Extracts were prepared through solid–liquid extraction and analyzed by high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS), enabling a comprehensive identification of bioactive metabolites. The analysis revealed a diverse profile of phenolic compounds, including hydroxytyrosol, tyrosol, and multiple oleuropein derivatives, as well as triterpenic acids such as oleanolic and maslinic acids. These compounds are widely recognized for their antioxidant, anti-inflammatory, and neuroprotective activities. The antioxidant potential of the extracts was evaluated in vitro using DPPH and ABTS radical scavenging assays, showing significant activity comparable to standard antioxidants. Moreover, cholinesterase inhibitory assays demonstrated moderate to strong inhibition of acetylcholinesterase, enzyme implicated in neurodegenerative diseases such as Alzheimer's disease. To further elucidate the molecular basis of these effects, in silico molecular docking studies were performed on the most abundant compounds, revealing favorable binding affinities and interactions with key active site residues of acetylcholinesterase. Overall, these findings highlight olive pomace as a promising, underutilized source of bioactive compounds with potential applications in the development of functional foods, nutraceuticals, and neuroprotective therapeutic agents. The integration of in vitro and in silico approaches strengthens the evidence supporting the use of these extracts in future biomedical and industrial applications.

The Aurora kinase A (Aurora-A), overexpressed in cancer cells, represents a promising anti-cancer therapeutic target due to its role in mitotic progression and chromosome instability [1]. Aurora-A contains a recently described drug pocket within its Targeting Protein for Xklp2 (TPX2) interaction site, offering a promising target for small-molecule disruption and selective inhibition [2]. In this study, 1281 natural products from Argentina's database (NaturAr), encompassing chemically diverse and structurally rich metabolites, were evaluated using a machine learning model based on molecular fingerprints and variational autoencoders (VAE) to predict inhibitory activity with high-throughput efficiency [3,4]. From this initial screening, 624 compounds were classified as active type against Aurora-A, and subsequently subjected to molecular docking using FRED software (v4.3.0.3) against the Aurora-A crystal structure (PDB: 5OSD), focusing on the TPX2-binding interface [2,5]. Among them, 117 compounds with various scaffolds showed better binding scores than the co-crystallized ligand, highlighting their potential to interact with the druggable target site through stable and specific molecular contacts. This workflow effectively prioritized compounds of natural origin from Argentina for the discovery of new Aurora-A kinase inhibitors, demonstrating the value of integrating AI-driven screening with structure-based modeling. These findings highlight the identification of novel scaffolds with high binding potential, offering promising starting points for the development of selective Aurora-A inhibitors.

In this study, a comprehensive computational simulation was conducted to investigate the structural, electronic, and biological properties of the syn and anti isomers derived from a Mannich-type three-component reaction (RMC) used for the synthesis of β-amino ketones, which are important intermediates in medicinal and synthetic organic chemistry. Density Functional Theory (DFT) calculations were employed to evaluate and compare the relative stability, reactivity, and electronic characteristics of both isomers. The results revealed that the syn isomer exhibits a larger HOMO–LUMO energy gap, indicating greater molecular stability and lower chemical reactivity, while the anti isomer displays a smaller energy gap, suggesting lower molecular stability but higher reactivity.

Subsequently, molecular docking studies were performed to assess the potential biological activity and binding behavior of both isomers toward the acetylcholinesterase (AChE) enzyme, a key therapeutic target in the treatment of neurodegenerative disorders such as Alzheimer’s disease. The docking results demonstrated that the anti isomer exhibits stronger binding affinity and, consequently, higher predicted biological activity, whereas the syn isomer shows weaker interactions and lower reactivity at the biological level.

These combined computational findings suggest a clear structure–activity relationship, where increased chemical reactivity and electronic flexibility correlate with enhanced molecular recognition and biological interaction in these Mannich-derived compounds.

Buchenavianine, or 7-hydroxy-5-methoxy-8-(1-methylpiperidin-2-yl)flavone along with its related compounds O-Demethylbuchenavianine, N-demethylbuchenavianine and N,O-bis(dimethyl)buchenavianine belong to the class of piperidine-flavonoid alkaloids, possessing a piperidine ring connected to the C8-position of the flavonoid skeleton. Buchenavianine derivatives have been primarily isolated from Buchenavia macrophylla and also found in B. capitata. Studies have suggested that buchenavianines may possess antiinflammatory, antioxidant, anti-HIV and anticancer properties. Understanding the biological activity of buchenavianine derivatives is crucial for assessing their potential as drug candidates considering factors such as pharmacokinetic and toxicity. The present study focuses on the in silico prediction of antibacterial, antiviral and antifungal activities using the AntiBac-pred, antiVir-pred and AntiFun-pred tools available on the Way2drug platform. Results are presented as confidence values indicating the likehood of inhibitory or non-inhibitory effects against specific pathogens (bacteria, viruses or fungi). The calculations suggest that natural buchenavianines under investigation are likely to exhibit antibacterial activity with confidence values ranging from 0.4980 to 0.3390 even against resistant bacterial strains. Antifungal activity was predicted with confidences of 0.1250 - 0.0274 while calculations of antiviral activity resulted in high confidence values of 0.8739 to 0.7500 highlighting their potential as antiviral agents. Toxicity assessments of buchenavianine derivatives were conducted using ProTox 3.0 software. The results indicate that all compounds would be non-toxic with a low probability of neurotoxicity and a high probability of respiratory toxicity.

This study focused on predicting the n-octanol/water partition coefficient (Kow) for a set of 56 pesticides using a quantitative structure-property relationship (QSPR) approach. The analysis used multiple linear regression (MLR) to relate the logarithm of Kow values (log Kow) to molecular descriptors derived from the chemical structures. The dataset was divided into a training set of 42 compounds and a test set of 14 compounds using the Kennard-Stone algorithm, which ensures even coverage of the descriptor space and improves the quality of external validation by reducing sampling bias.

The molecular descriptors were calculated using Dragon software. A genetic algorithm (GA) combined with a variable subset selection (VSS) procedure was employed to identify and retain the most informative descriptors. This approach helped to build a predictive model with reduced complexity and enhanced interpretability.

The model showed strong statistical performance, with R² = 93.22, Q²LOO = 90.89, Q²ext = 92.77, SDEC = 0.450, SDEP = 0.520, SDEPext = 0.546, F = 92.4052, and s = 0.511. Internal cross-validation and external test set validation confirmed the model’s robustness, reliability, and predictive power.

These results support the use of the model as a reliable and practical tool for predicting Kow values of pesticides. It contributes to environmental and chemical risk assessments by enabling better evaluation of the environmental behavior, bioaccumulation, and toxicity of pesticide compounds.

Recent advances in computational drug discovery have significantly improved the search for effective treatments for skin cancer, where molecular docking and pharmacokinetics play an important role in identifying new drug-like compounds. This study explores the inhibitory potential of pyrrolopyrazole (4BKY), an enzyme linked to skin cancer progression, using 62 cytotoxic quinoline derivatives.Among these, Ligand 7 and Ligand 10 demonstrated the strongest binding affinities, with docking scores of -6.722 kcal/mol and -6.606 kcal/mol, respectively. Their enhanced stability and interaction with key residues GLU 87 and CYS 89 suggest promising inhibitory properties. In addition to docking analysis, these compounds underwent ADMET (Absorption, Distribution, Metabolism, and Excretion) analysis profiling using SWISSADME, pkCSM, to assess their pharmacokinetic Additionally, toxicity assessment was performed using the ProTox-II web server (https://tox-new.charite.de/protox_II/), predicting mutagenicity, carcinogenicity, immunotoxicity, and hepatic toxicity.. Findings indicate favorable drug-likeness, efficient synthesis, and compliance with Lipinski’s rule of five, supporting their viability as targeted skin cancer therapeutics. Based on these results, Ligand 7 and Ligand 10 emerge as strong candidates for further research and development in oncology. Future studies will focus on experimental validation and clinical trials to confirm their effectiveness and safety, potentially paving the way for innovative skin cancer treatment strategies involving quinoline-based compounds.

Because of fossil fuel depletion and its inevitable hazard to the environment researchers have worked on alternative fuel sources like Hydrogen (H₂) which can be obtained via renewable energy sources like biomass, solar, geothermal, ocean, wind, hydropower, and nuclear. H₂ has many advantages. It has a high heating value compared to traditional fossil fuels. It can be synthesized from water or biomass without releasing any Greenhouse Gases (GHGs) Emission. Nowadays, the most popular hydrogen production methods are sodium borohydride (NaBH₄) hydrolysis, photocatalysis, and water electrolysis. Among them, the NaBH₄ hydrolysis reaction is preferred due to its advantages. It can be possible to reach high hydrogen generation rates under mild conditions with this reaction. In this work, thermodynamic analysis was carried out with Gauss software. At first, the products and reactants of the reaction were drawn. Then enthalpy and free energy information were taken for the reaction. Calculations were done via the Hartree-Fock Method for each molecule. Basis Set was selected as 6-31G(d). Reaction conditions were assumed as 298 K and 1 atm. As a result of the computations, the Enthalpy and Free Energy of the reaction were found as -58.0315 kcal/mol and -72.6141 kcal/mol respectively. This meant that this reaction was exothermic because of the negative sign of enthalpy. Besides that, the negative sign of Gibbs Energy was related to spontaneous reaction.

The importance of 1,2,4-triazole derivatives in modern pharmaceuticals is very high. They find their application in drug therapy as antifungal, antifungal agents (fluconazole, intraconazole). It is worth noting that some 1,2,4-triazole compounds are used in therapy for the treatment of Alzheimer's disease, and new, more effective pharmacophores are being sought to create drugs for neurodegenerative diseases. We have proposed a modernized method for obtaining a new bis(1,2,4-triazole) derivative using the recyclization reaction of 4-hydroxy-2,5-disubstituted-1,3-6H-oxazin-6-ones with a bisnucleophilic reagent, which was m-phenylenedihydrazine. The method of preparation described in the literature did not lead to the expected products, so it was necessary to select new reaction conditions. 1,1′-(benzene-1,3-diyl)bis[5-benzyl-3-(4-nitrophenyl)-1H-1,2,4-triazole] was obtained by recyclization of 4-hydroxy-2-(4-nitrophenyl)-5-phenyl-6H-1,3-oxazin-6-one with m-phenylenedihydrazine dihydrochloride in absolute methanol in the presence of sodium methoxide for 48 hours. The structure of the compound was confirmed by 1H, 13C NMR spectroscopy and mass spectrometry. Antifungal and antibacterial activities were determined by serial dilutions using meat-peptone broth and Sabouraud medium. The yield based on 4-hydroxy-2-(4-nitrophenyl)-5-phenyl-6H-1,3-oxazin-6-one was 76%. The obtained compound exhibits antimicrobial activity against Staphylococcus aureus with a minimum inhibitory concentration of 62.5 μg/ml and 125 μg/ml against Candida albicans.

Recently, there has been a growing interest in multifunctional materials, therefore we developed a system that combines biocompatibility, gradient changing and antibacterial properties. We aim to combine these properties in the development of a biomimetic system based on hydroxyapatite (Ca₁₀ (PO₄)₆ (OH)₂, HA) by incorporating silver nanoparticles (Ag NPs) into HA matrices, leveraging their antimicrobial effects, while also exploring their role as drug release triggers (absorb infrared (IR) light of 808-960 nm, convert to heat energy to induce localized heating and cause a structure leak for drug release) to unmodified HA which cannot be activated by IR in significant amounts. Limited diffusion aggregation is used to form HA (enhanced with glycine or produced with different outer electrolytes) by diffusing calcium phosphates through Na₂HPO₄-agar. The composite was then packed with tetracycline and deposition of polyelectrolytes (PE). The combination of polydiallyldimethylammonium chloride (PDADMAC) and heparin forms a robust PE. Infrared light (808 nm, 1.4 mW/cm²) was utilized as energy source for non-invasive and on-demand drug release. Physical and chemical characterization of HA was carried out. Glycine did not affect the p-factor of the resulting rings, which is equal to ca. 1.00. NIR increased release rates 2.1-fold (k = 39.21 compared to 18.22). High glycine concentrations reduces HA crystallinity (94 to 30%), a 12.5% increased drug loading capacity, increases solubility (5× control). NIR reduced the Korsmeyer-Peppas release exponent (n) from 0.42 (Fickian) to 0.11 (PE-coated HA-Ag), confirming photothermal disruption of diffusion barriers due to the presence of silver nanoparticle peaks in the composition.