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Bacterial resistance to antibiotics remains a significant clinical challenge, contributing to persistently high rates of morbidity and mortality. Achieving treatment success is increasingly difficult, necessitating the evaluation of new antibiotics and complementary approaches, including source control and alternative therapies. This study aimed to investigate the antibacterial, antioxidant, cytotoxic, and phytochemical properties of Moringa oleifera leaf extract using high-performance liquid chromatography (HPLC), and to evaluate the pharmacokinetic properties of its major compound. The extract demonstrated strong antibacterial activity against standard strains and foodborne bacterial species. It also showed significant antioxidant potential, supported by the presence of high concentrations of phenolic and flavonoid compounds. HPLC analysis identified multiple bioactive compounds, with quercetin as the predominant component. The cytotoxicity study confirmed the safety of the extract at low and moderate concentrations, and ADMET analysis indicated favorable pharmacokinetic characteristics of quercetin. In conclusion, Moringa oleifera exhibits promising potential for medical and food industry applications due to its significant antibacterial and antioxidant activities, combined with a strong safety profile and rich phytochemical content.

Atriplex halimus L., also known as Mediterranean saltbush, and locally as “Lgtef”, an halophytic shrub, is used extensively to treat a wide variety of ailments in Morocco. The present study was undertaken to determine the antioxidant activity and cytotoxicity of the ethanolic extract of A. halimus leaves (AHEE). We first determined the phytochemical composition of AHEE using a liquid chromatography (LC)–tandem mass spectrometry (MS/MS) technique. The antioxidant activity was evaluated using different methods including DPPH scavenging capacity, β-carotene bleaching assay, ABTS scavenging, iron chelation, and the total antioxidant capacity assays. Cytotoxicity was investigated against human cancer breast cells lines MCF-7 and MDA-MB-231. The results showed that the components of the extract are composed of phenolic acids and flavonoids. The DPPH test showed strong scavenging capacity for the leaf extract (IC50 of 0.36 ± 0.05 mg/mL) in comparison to ascorbic acid (IC50 of 0.19 ± 0.02 mg/mL). The β-carotene test determined an IC50 of 2.91 ± 0.14 mg/mL. The IC50 values of ABTS, iron chelation, and TAC tests were 44.10 ± 2.92 TE µmol/mL, 27.40 ± 1.46 mg/mL, and 124 ± 1.27 µg AAE/mg, respectively. In vitro, the AHE extract showed significant inhibitory activity in all tested tumor cell lines, and the inhibition activity was found in a dose-dependent manner. Furthermore, computational techniques such as molecular docking and ADMET analysis were used in this work. Moreover, the physicochemical parameters related to the compounds’ pharmacokinetic indicators were evaluated, including absorption, distribution, metabolism, excretion, and toxicity prediction (Pro-Tox II).

Globally, cancer is the second leading cause of mortality and morbidity. The growth and development of cancer are extremely complex. It is caused by a variety of pathways and involves various types of enzymes. Pyruvate kinase M2 (PKM2) is an isoform of pyruvate kinase, that catalyses the last steps of glycolysis to produce energy. PKM2 is relatively more expressed in tumour cells where it tends to exist in a dimer form. Various medicinal plants are available that contain a variety of micronutrients to combat against different cancers. The phytocompounds of the olive tree (Olea europaea) leaves play an important role in inhibiting the proliferation of several cancers. In this study, the phytocompounds of olive leaf extract (OLE) were studied using various in silico tools, such as pkCSM software to predict ADMET properties and PASS Online software to predict anticancer activity. However, the molecular docking study provided the binding energies and inhibition constant and confirmed the interaction between PKM2 and the ligands. The dynamic behaviour, conformational changes, and stability between PKM2 and the top three hit compounds (Verbascoside (Ver), Rutin (Rut), and Luteolin_7_O_glucoside (Lut)) are studied by MD simulations.

Topological indices are invariant quantitative metrics associated with a molecular graph, which characterize the bonding topology of a molecule. The main aim of analyzing topological indices is to summarize and transform chemical structural information, thus creating a mathematical relationship between structures and their physico-chemical properties, biological activities, and other experimental characteristics. Quantitative Structure-Property Relationships (QSPR) and Quantitative Structure-Activity Relationships (QSAR) utilize topological indices to correlate diverse molecular properties, including physico-chemical, thermodynamic, chemical, and biological activities, with their chemical structures. Parkinson’s disease is marked by persistent psychosis due to cognitive deficits. Extended compliance with medication and therapy generally reduces symptoms. Factors such as solubility, metabolic stability, toxicity, permeability, and transporter interactions significantly impact the efficacy of drug design and are dependent on the physical and chemical properties involved. Computational tools for the discovery and development of medications for Parkinson’s disease have recently gained prominence. Various methods evaluate therapeutic efficacy and adverse effects utilizing machine learning techniques. Further research has utilized computer simulations to explore the molecular mechanisms of the disease and to identify new therapeutic targets. This research investigates the predictive capacity of nine physico-chemical and thirteen pharmacokinetic parameters (ADMET) by utilizing both open and closed neighborhood degree-sum-based descriptors for twelve drugs used in the treatment of Parkinson’s disease. The study employs linear, quadratic, cubic, and multiple linear regression models. A comparative analysis is conducted using several well-known degree-based indices alongside the selected open and closed neighborhood degree-sum-based indices within both univariate and multivariate regression methodologies.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has fomented a climate of fear worldwide due to its rapidly spreading nature, and high mortality rate. The World Health Organization (WHO) declared it as a global pandemic on 11 th March, 2020. Many endeavors have been made to find appropriate medications to restrain the SARS CoV-2 infection from spreading but there is no specific antiviral therapy to date. However, a computer-aided drug design approach can be an alternative to identify probable drug candidates within a short time. SARS-CoV-2 main protease is a proven drug target, and it plays a pivotal role in viral replication and transcription. Methods: In this study, we identified a total of 114 essential oil compounds as a feasible anti-SARS-CoV-2 agent from several online reservoirs. These compounds were screened by incorporating ADMET profiling, molecular docking, and 50 ns of molecular dynamics simulation to identify potential drug candidates against the SARS-CoV-2 main protease. The crystallized SARS-CoV-2 main protease structure was collected from the RCSB PDB database (PDB ID 6LU7). Results: According to the results of the ADMET study, none of the compounds have any side effects that could reduce their druglikeness or pharmacokinetic properties. Out of 114 compounds, we selected bisabololoxide B, eremanthin, and leptospermone as our top drug candidates based on their higher binding affinity scores, and strong interaction with the Cys 145-His 41 catalytic dyad. Finally, the molecular dynamics simulation was implemented to evaluate the structural stability of the ligand-receptor complex. MD simulations disclosed that all the hits showed conformational stability compared to the positive control α-ketoamide. Conclusions : Our study showed that the top three hits might work as potential anti-SARS-CoV-2 agents, which can pave the way for discovering new drugs, but for experimental validation, they will require more in vivo trials.

A computational screening for natural compounds suitable to bind the AKT protein has been performed after the generation of a pharmacophore model based on the experimental structure of AKT1 complexed with IQO, a well-known inhibitor. The compounds resulted as being most suitable from the screening have been further investigated by molecular docking, ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analysis and toxicity profiles. Two compounds selected at the end of the computational analysis, i.e., ZINC2429155 (also named STL1) and ZINC1447881 (also named AC1), have been tested in an experimental assay, together with IQO as a positive control and quercetin as a negative control. Only STL1 clearly inhibited AKT activation negatively modulating the PI3K/AKT pathway.

Background and Objectives: Alzheimer’s disease (AD) stands as a pervasive neurodegenerative ailment of global concern, necessitating a relentless pursuit of remedies. This study aims to furnish a comprehensive exposition, delving into the intricate mechanistic actions of medicinal herbs and phytochemicals. Furthermore, we assess the potential of these compounds in inhibiting human acetylcholinesterase through molecular docking, presenting encouraging avenues for AD therapeutics. Materials and Methods: Our approach entailed a systematic exploration of phytochemicals like curcumin, gedunin, quercetin, resveratrol, nobiletin, fisetin, and berberine, targeting their capability as human acetylcholinesterase (AChE) inhibitors, leveraging the PubChem database. Diverse bioinformatics techniques were harnessed to scrutinize molecular docking, ADMET (absorption, distribution, metabolism, excretion, and toxicity), and adherence to Lipinski’s rule of five. Results: Results notably underscored the substantial binding affinities of all ligands with specific amino acid residues within AChE. Remarkably, gedunin exhibited a superior binding affinity (−8.7 kcal/mol) compared to the reference standard. Conclusions: These outcomes accentuate the potential of these seven compounds as viable candidates for oral medication in AD treatment. Notably, both resveratrol and berberine demonstrated the capacity to traverse the blood-brain barrier (BBB), signaling their aptitude for central nervous system targeting. Consequently, these seven molecules are considered orally druggable, potentially surpassing the efficacy of the conventional drug, donepezil, in managing neurodegenerative disorders.

Nine novel functionalized 2,5-diaryloxazolo[4,5- d ]pyrimidin-7-ylamines were designed, synthesized and characterized using 1 H, 13 C NMR, IR spectroscopy, elemental analysis, and liquid chromatography–mass spectrometry . Their anticancer activity was assessed against human cancer cell as well as non-cancer cell lines. Three compounds, 1 , 3 , and 9 , were the most cytotoxic to HeLa cells (IC 50 = 6.13 ± 1.95, 13.99 ± 1.80 and 49.92 ± 3.98 μM, respectively). However, only compounds 1 , 7 , and 9 were selective against the tested lines. Compound 9 can be classified as the most attractive and promising candidate for further development against cervical adenocarcinoma.

Encephalitis is a life-threatening neurological condition characterized by extensive neuroinflammation, with tumor necrosis factor-α (TNF-α) playing a central role in disease progression. Current antiviral and antibacterial therapies are limited by poor brain penetration, drug resistance, and inadequate control of inflammatory cascades. This study employed Computer-Aided Drug Design (CADD) to identify novel isatin-based small molecules capable of modulating TNF-α activity. The TNF-α structure (PDB ID: 2AZ5) was validated using PROCHECK, VERIFY3D, and SWISS-MODEL, confirming its suitability for computational screening. Three rationally designed isatin derivatives (Ligand-A, Ligand-B, Ligand-C) and standard encephalitis drugs (acyclovir, ganciclovir, ceftriaxone) were docked using AutoDock Vina to compare their binding profiles. As expected, clinically used drugs showed minimal affinity for TNF-α, serving only as computational controls. The designed ligands exhibited significantly stronger binding affinities (–9.3 to –9.1 kcal/mol), stabilizing through hydrogen bonding, π–π interactions, and hydrophobic contacts within the TNF-α binding pocket. ADMET evaluation indicated favorable oral absorption, drug-likeness, and BBB permeability for all three compounds. However, Ligand-B showed a moderate probability of hepatotoxicity, suggesting the need for structural optimization. Overall, these results identify isatin derivatives as promising preliminary hits with potential relevance in targeting neuroinflammatory pathways associated with encephalitis. Further optimization and experimental validation are required to advance these candidates toward therapeutic development. [Display omitted]

The Epidermal Growth Factor Receptor (EGFR) is a transmembrane tyrosine kinase receptor that regulates key cellular processes such as proliferation, differentiation, and survival. Aberrant activation or overexpression of EGFR has been extensively associated with the onset and progression of various malignancies, including lung, breast, and colorectal cancers. Consequently, EGFR has emerged as a validated molecular target for the design of novel anticancer therapeutics. Sulfonyl hydrazone derivatives constitute a versatile class of organic compounds exhibiting a wide spectrum of biological activities, such as antimicrobial, anti-inflammatory, and anticancer effects. Their structural flexibility, presence of electron-donating and withdrawing substituents, and ability to form stable interactions with biological macromolecules make them promising scaffolds for the development of potent EGFR inhibitors with improved pharmacological profiles. To synthesize and comprehensively evaluate the structural, electronic, optical, and biological properties of a novel sulfonyl hydrazone derivative, N′-([1,1′-biphenyl]-4-ylmethylene)-4-methylbenzenesulfonohydrazide (BMBSH), as a potential EGFR inhibitor. BMBSH was synthesized via condensation of 4-methylbenzenesulfonohydrazide with [1,1′-biphenyl]-4-carbaldehyde using H₂SO₄ as a catalyst. The compound was characterized using FT-IR, ¹H NMR, and ¹ ³C NMR. Computational studies included DFT optimization, MEP and Mulliken analyses, molecular docking, 100 ns molecular dynamics (MD) simulation, and ADMET profiling. Spectroscopic data confirmed the formation of the hydrazone linkage and the imine (CN) bond. DFT results (HOMO–LUMO gap 4.215 eV) indicated strong electronic stability and close agreement with experimental data. BMBSH showed high nonlinear optical activity (β₀ = 2.939 × 10⁻³⁰ esu). Docking and MD studies demonstrated stable EGFR binding through hydrogen bonds and π–π interactions, with better stability than doxorubicin. ADMET analysis showed excellent intestinal absorption (92.86 %), blood–brain barrier penetration, and favorable bioavailability (0.55). BMBSH is a structurally stable, electronically robust, and pharmacologically promising EGFR inhibitor with strong binding affinity, superior stability, and good drug-like properties. These results highlight its potential as a lead compound for future anticancer drug design integrating synthetic and computational approaches. [Display omitted] •Synthesis of novel hydrazone derivatives confirmed by FT-IR and NMR spectral techniques.•Investigation of electronic properties through DFT-based analysis.•Molecular docking and Dynamics simulation analysis to evaluate the inhibitory potential of the synthesized compound.•ADMET analysis was examined.