Abstract: Quinoxaline derivatives are a vital class of compounds, with 2,3-diphenylquinoxaline (DPQ) being particularly important for its applications in pharmacology and material science. However, traditional methods for its synthesis often rely on harsh conditions and environmentally harmful solvents, creating a need for greener alternatives. Addressing this challenge, we present a highly efficient, sustainable, and versatile one-pot method for synthesizing DPQ. This approach is centered on green chemistry principles, utilizing sodium hypochlorite (NaOCl·5H₂O) as an inexpensive and eco-friendly oxidant.

The synthesis involves the oxidation of benzoin and its subsequent condensation with o-phenylenediamine within a benign ethanol/water solvent system. A key strength of this method is its remarkable adaptability; the reaction performs exceptionally well under several conditions, affording excellent yields of 96% with a photochemical reactor, 92% under standard reflux, and 83% in an electrochemical cell. The successful synthesis and high purity of the DPQ product were confirmed through comprehensive characterization, including ¹H and ¹³C NMR spectroscopy.

To provide deeper mechanistic insight, the reaction was modeled using Density Functional Theory (DFT) calculations. These studies elucidated a favorable reaction pathway involving the formation of aminol and diaminol intermediates, identifying key energetic barriers for the proton transfer steps. By successfully integrating multiple green-by-design strategies with detailed computational validation, this research provides a robust and accessible blueprint for the clean production of valuable quinoxaline derivatives, championing the broader adoption of sustainable practices in modern organic synthesis.

Chalcones are interesting compounds because of their pharmacological versatility, in this work a series of three nitro-substituted chalcones (compounds 3a–c), modified at the B aromatic ring, was synthesized via a classical Claisen–Schmidt condensation under mild hydroalcoholic conditions at room temperature. This method proved efficient and reproducible, affording excellent yields above 90% for all three derivatives. Structural elucidation was achieved through spectroscopic techniques including IR, ¹H and ¹³C NMR, all of which confirmed the expected α,β-unsaturated ketone frameworks with nitro substitutions. To evaluate the anti-inflammatory potential of the synthesized compounds, an in vivo carrageenan-induced hind paw edema model in rats was employed. This model is widely used for assessing acute inflammatory responses. Compounds 3a–c were administered prior to carrageenan injection, and paw volume was measured over time. All compounds demonstrated a significant protective effect against inflammation, with compound 3b showing the highest activity within the series. The anti-inflammatory data were analyzed statistically using ANOVA followed by Tukey’s post hoc test. Additionally, a comparative analysis was conducted between these B-ring-substituted nitrochalcones and previously reported chalcones bearing substitutions on ring A. The findings suggest that the position and nature of substitution play a crucial role in modulating anti-inflammatory activity, highlighting the potential of nitrochalcones as candidates for further pharmacological development.

Paracetamol (acetaminophen) is widely used as an analgesic and antipyretic; however, overdose results in hepatotoxicity primarily mediated through its toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). This study aims to explore the hepatoprotective potential of selected phytochemicals—silymarin, piperine, quercetin, and gallic acid—through molecular docking against key proteins implicated in paracetamol-induced liver injury. In silico docking studies were performed using Schrödinger Release 2021-4 on a high-performance Ubuntu workstation. Ligands were sketched in Maestro, processed via LigPrep under OPLS_2005 force field conditions, and docked using Glide in XP mode. Seven protein targets were selected: succinate dehydrogenase (SDH), glutathione reductase (GSHR), cyclooxygenase-2 (Cox2), TNF-α, IL-6, IL-1β, and JNK, representing key pathways including mitochondrial dysfunction, oxidative stress, and inflammation. The results revealed that quercetin exhibited the strongest binding affinities across all targets, with a notable docking score of –9.060 for JNK and –8.027 for IL-1β, suggesting potent anti-inflammatory and mitochondrial protective roles. Gallic acid demonstrated broad-spectrum efficacy, especially against GSHR (–5.288) and JNK (–8.052), implicating its antioxidant potential. Silymarin showed significant binding to Cox2 (–7.073) and SDH (–5.665), supporting its known hepatoprotective effect. Piperine, while moderate in most targets, showed enhanced affinity for Cox2 (–6.608), indicating anti-inflammatory relevance. Overall, the study highlights quercetin and gallic acid as promising phytochemicals that may counteract paracetamol-induced hepatotoxicity by targeting multiple pathophysiological proteins. Further in vitro and in vivo validations are warranted to establish their therapeutic potential.

The global population is aging rapidly, with those aged 60 and above expected to reach 2.1 billion by 2050. This shift is driving a rise in chronic diseases, including diabetes, which is projected to affect 592 million people by 2035. These trends highlight the urgent need for novel therapeutic strategies and better understanding of disease mechanisms.

Resveratrol and quercetin, two widely recognized polyphenols, are highly valued for their potent antioxidant and anti-inflammatory properties, demonstrating significant promise in mitigating and improving diabetic conditions by addressing core pathological features such as oxidative stress and insulin resistance. This study leverages computational chemistry techniques to elucidate the putative mechanisms of action of resveratrol and quercetin within the context of diabetic pathogenesis. To achieve this, a target prediction analysis was performed for both molecules using SwissTargetPrediction and EpigeneticTargetProfiler, followed by a structure-based target fishing utilizing TargetFisher. From the list of the predicted targets, we selected three key enzymes: Monoamine Oxidase A (MAO-A) and Monoamine Oxidase B (MAO-B), mitochondrial enzymes linked to oxidative stress and inflammation in diabetic conditions, and Insulin-like Growth Factor 1 Receptor (IGF-1R), which activates signalling pathways essential for insulin sensitivity and beta-cell function. These targets were chosen due to their established roles in metabolic signaling and oxidative pathways relevant to diabetes progression. Molecular docking analyses indicated the potential of quercetin and resveratrol to modulate the function of these enzymes and to confirm viability to continue exploring the therapeutic potential of these natural products in both combating metabolic aging and managing diabetic disease.

Introductions
The study is devoted to the photochemically initiated interaction
between nitromethane and hydrazine. The reaction mechanism includes an
oxygen atom transfer from the triplet state nitrocompound to N-atom of
organic nitrogen-containing compounds.
Research methods
Quantum-chemical calculations were carried out using the Gaussian 09
software package. The calculations included the DFT methods such as the
B3LYP, B3PW91 and ωB97XD in combination with various basis sets.
Particular attention was paid to the search for transition states
structures.
Research Results
As a result of the study, the following tasks were successfully solved:
the mechanism of photochemical transfer of an oxygen atom from a triplet
nitromethane molecule to a hydrazine molecule was determined, the
geometric characteristics of all reaction participants, including
reagents and the transition state, the energy barrier of the process was
calculated, and a detailed analysis of the spin density distribution was
carried out.

The reaction scheme was proposed as:

RNO2 + hv => 1RNO2* ~~isc~~> 3RNO2

3RNO2 + R1R2N - NR3N4 => 3[RN(O)...O…NR1R2 - NR3R4]

3[RN(O)...O…NR1R2 -- NR3R4] ~~isc~~> RN=O + O=NR1R2- NR3R4
Conclusions
The research proved the direct oxygen atom transfer as the main reaction pathway without charge transfer processes. Calculated activation energy values confirm the proposed mechanism feasibility. These results provide a basis for developing innovative nitrogen-containing compounds disposal methods.

The sulfonamide group represents a crucial functional moiety in both organic synthesis and pharmaceutical development. sulfonamides exhibit remarkable chemical stability and unique reactivity, making them valuable intermediates and end-products in a wide range of chemical transformations. Historically, sulfonamide derivatives gained prominence as the first class of synthetic antibiotics, revolutionizing antimicrobial therapy in the early 20th century. Beyond their antibacterial properties, sulfonamides have demonstrated a broad spectrum of biological activities, including antidiabetic, antitumor, and anti-inflammatory effects.On the other hand, computational chemistry plays a pivotal role in the rational design and development of novel sulfonamide-based molecules with potential biological or industrial applications. Through advanced molecular modeling, quantum chemical calculations, and molecular docking techniques. These in silico methods enable efficient screening of large libraries of sulfonamide analogs, identification of promising lead compounds, and optimization of their pharmacokinetic and pharmacodynamic profiles. Moreover, density molecular dynamics simulations offer valuable insights into the geometry, stability, and interaction mechanisms of these compounds at the atomic level.In the present study, a series of sulfonylimine derivatives were synthesized via the condensation of aromatic aldehydes with sulfanilamide, yielding the target compounds in good yields. To investigate their therapeutic potential particularly as anti-inflammatory agents, molecular docking studies were performed against phosphodiesterase 4 (PDE4), a key enzyme involved in the regulation of inflammatory responses through modulation of intracellular cyclic adenosine monophosphate (cAMP) levels. Inhibition of PDE4 results in elevated cAMP concentrations, which activate protein phosphorylation cascades that suppress the production of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α).

Introduction: Acinetobacter baumannii is a multidrug-resistant pathogen from the ESKAPE group, associated with nosocomial infections. Its resistance to multiple antibiotics poses a global threat. The QACE protein, an efflux pump, has been identified as a key resistance mechanism, making it a promising target for the development of new antibacterial agents.

Objective: To identify low molecular weight compounds derived from natural products with potential inhibitory activity against the QACE protein, using virtual screening and molecular docking studies.

Materials and Methods: The three-dimensional structure of QACE was retrieved from AlphaFold, followed by energy minimization and assignment of Kollman-type charges. Ligand screening was performed using the BioMX database through structural similarity analysis (Tanimoto coefficient ≥ 0.85), using ciprofloxacin as the reference compound. Selected molecules were evaluated using SwissADME to predict their pharmacokinetic properties, and three candidates with favorable profiles were chosen. Molecular docking studies were then performed using AutoDock 4 to estimate binding affinities.

Results: Voacangine was the compound with the highest structural similarity, strongest binding affinity to QACE (ΔG = -6.2 kcal/mol; Ki = 28.51 μM), and stable molecular interactions including hydrogen bonds and π-stacking. It showed favorable tissue distribution, low potential for CYP3A4 inhibition, and minimal predicted cardiotoxicity (hERG channel blockade).

Conclusion: Voacangine emerges as a promising candidate for inhibiting the QACE efflux pump in Acinetobacter baumannii. This study highlights the value of computer-aided drug design as an effective strategy in the search for new treatments against multidrug-resistant bacteria.

Introduction: It is generally known that quinoline derivatives, particularly those that inhibit lipase and reductase, are strong antimicrobial agents. Several commercially available drugs, such as Bosutinib and Lenvatinib, are based on quinoline scaffolds.

Objective: The current research focused on the design and synthesis of novel quinoline derivatives, aiming to investigate their potential as multitarget enzyme receptor inhibitor and further evaluated for in-silico Antimicrobial Activity.

Methods: The named compounds were made primarily in three stages. Substituted Carboxylic acids of quinoline were synthesized using differently substituted isatins and acetophenones according to the Pfitzinger reaction. Benzotriazole-amines were synthesized in a second step, and the final compounds were obtained by reacting both of the intermediates in the presence of a base.

Results: Molecular docking studies were performed using the E. coli MsbA protein (PDB ID: 6BPP), which is in complex with lipopolysaccharide (LPS) and the inhibitor G092. Five designed compounds (5a–5e) were docked to evaluate their binding affinities. For screening, Lipinski’s Rule of Five and ADME (Absorption, Distribution, Metabolism, and Excretion) properties were analyzed using computational pharmacology tools alongside docking scores.

Conclusion: All synthesized compounds successfully passed the initial in silico screening. Among them, compounds 5a and 5d complied with Lipinski’s criteria and showed promising binding affinities. Compound 5a exhibited the strongest binding with a score of −8.7, while 5e also demonstrated notable affinity with a docking score of −8.3.

References:

1. Ali, M.R.; Kumar, S.; Afzal, O.; Shalmali, N.; Ali, W.; Sharma, M.;Bawa, S., Arch Pharm Chemistry in Life Sciences. 350, 2017, e1600313.

Phosphoinositide 3-kinase (PI3K) represents a pivotal therapeutic target implicated in cellular proliferation, metabolic processes, and oncogenic mechanisms. This research delineates a comprehensive in silico methodology aimed at identifying effective and pharmacokinetically favorable inhibitors of PI3K. Structure-based molecular docking was executed targeting the ATP-binding pocket of PI3K, revealing that the highest-ranked compound, MOL ID: 11325, demonstrated a significant binding affinity, reflected by a docking score of –8.558 kcal/mol.
ADMET and SwissADME profiling confirmed that molecule 11325 is Lipinski-compliant, P-gp non-substrate, has a bioavailability score of 0.55, no PAINS or Brenk alerts, and a favorable synthetic accessibility (2.68), supporting its drug-likeness and development potential.. A 100 ns molecular dynamics simulation confirmed the stability of the PI3K–ligand complex, demonstrating minimal deviations in root mean square deviation (RMSD) and root mean square fluctuation (RMSF). The binding free energy, determined through the MMGBSA method, exhibited a favorable value (ΔG_bind ≈ –58.6 kcal/mol), thereby corroborating the ligand's affinity. The FEL analysis revealed distinct low-energy states, while the PCA indicated minimal structural fluctuations, confirming a stable and specific binding mode. Molecule 11325 was designated as a novel, drug-like, and dynamically stable PI3K inhibitor by this integrated computational approach, indicating that it requires additional preclinical validation for therapeutic development.

The TEA domain (TEAD) transcription factors are important parts of the Hippo signaling cascade and are important therapeutic targets in cancer research because they help control cell growth, avoid apoptosis, and cause tumors to form. In this study, a structure-based virtual screening method was used to find new TEAD antagonists in the ChemDiv natural product database. Using the AutoDock platform for molecular docking, we ranked eight candidate ligands—16956, 726, 5271, 11768, 12384, 15598, 15641, and 3622—based on strong binding affinities, as shown by docking energies that ranged from –8.02 to –8.49 kcal/mol. Swiss ADME's full in silico ADMET profile showed that all of the selected compounds had good pharmacokinetic properties and did not break Lipinski's rule of five, which means they would be quite bioavailable when taken by mouth. Two lead candidates, 11768 and 15598, did not pass across the blood-brain barrier (BBB) and were not substrates for P-glycoprotein. This means that they had less exposure to the central nervous system and a lower chance of developing multidrug resistance. Later molecular dynamics (MD) simulations verified that the ligand–TEAD complexes were stable in their shapes, and MMGBSA (Molecular Mechanics/Generalized Born Surface Area) free energy calculations indicated that they had high-affinity binding. Principal component analysis and free energy landscape tests helped to explain even more the dynamic behavior and thermodynamic landscapes of the complexes. This integrated computational technique helped us find strong, drug-like TEAD inhibitors in a logical way. It also gave us a solid base for further preclinical testing and structural optimization in the creation of targeted anticancer drugs.