This investigation employs Molecular Electron Density Theory (MEDT) to elucidate the stereoselective (4+2) cycloaddition between 1-(furan-2-yl)propan-1-one and 1-R-1H-pyrrole-2,5-dione, combining mechanistic and pharmacological analyses. DFT calculations at the M06/6-311++G(d,p) level identified six distinct reaction pathways, revealing the exo cycloadduct as the thermodynamically favored product, consistent with experimental observations. Transition state analysis through NCI revealed stabilizing CH-π and van der Waals interactions governing the exo preference. Beyond mechanistic insights, the derived norcantharimide analogues exhibit promising anticancer potential, with strong binding affinities against hematological malignancy targets. SwissADME profiling confirmed optimal drug-likeness (QED > 0.6, TPSA < 100 Ų) and low hepatotoxicity risk. Notably, molecular dynamics simulations established exceptional stability for lead compound P2d (RMSD 75%) to key catalytic residues. These integrated computational results position these derivatives as viable candidates for blood cancer therapeutics, merging rigorous mechanistic understanding with preclinical potential assessment.

The method for the synthesis of ethyl 4-[3-(ethoxycarbonyl)-1-phenyl-1H-pyrazol-4-yl]-2-oxo/thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates was developed, and the bioactivity of the obtained compounds against infectious agents was predicted. Docking studies of the synthesised compounds were performed on pteridine reductase 1 (PTR1) of Leishmania, dihydrofolate reductase–thymidylate synthase of Trypanosoma cruzi, and human dihydrofolate reductase. The results demonstrated that the investigated compounds exhibit high affinity for these enzymes. Moderate selectivity relative to human DHFR was also observed. In addition, the predicted drug-likeness, ADME-Tox parameters, and toxicity profiles suggest the potential of the synthesised compounds for further pharmacological development.

This study highlights the dual functionality of caffeine extracted from spent coffee grounds as both a green corrosion inhibitor and a potential broad-spectrum therapeutic agent. Using DFT (B3LYP/6‑311G(d,p)), caffeine exhibited favorable electronic properties (ΔEgap = 4.42 eV, dipole moment = 5.21 D), supporting its strong adsorption capabilities. Molecular Dynamics simulations under acidic conditions confirmed stable, near-flat adsorption on Fe(110), Cu(111), and Al(111) surfaces, with significant interaction energies, indicating robust protective behavior. Simultaneously, molecular docking revealed promising binding affinities of caffeine to SARS-CoV-2 Mpro and Plasmodium falciparum kinases, suggesting antiviral and anti-malarial potential. This theoretical work demonstrates caffeine’s value as a sustainable, multifunctional molecule with applications in both corrosion control and drug discovery.

Alkylpyrimidine derivatives, particularly thiopental-based analogs, have emerged as promising scaffolds for antimicrobial drug development. In this study, we designed and synthesized a series of novel thiopental-pyrimidine hybrids (3a–c, 4) through efficient condensation reactions, and characterized these compounds by using NMR, IR, and mass spectrometry. Antimicrobial screening revealed significant activity against clinically relevant strains: derivative 3a exhibited selective inhibition of Bacillus subtilis (MIC: 10.5±0.4 mg/mL) and Escherichia coli (MIC: 22.1±0.3 mg/mL), while 3c showed potent antifungal effects against Candida albicans (MIC: 11.6±0.4 mg/mL). Molecular docking studies elucidated the mechanistic basis of this activity, with 3a binding to penicillin-binding protein (PBP; −6.4 kcal/mol) via hydrogen bonds (SER392) and hydrophobic interactions (TYR430, PRO660), and 3c coordinating with the heme iron of CYP51 (−7.8 kcal/mol) akin to fluconazole. Notably, 3c thioether linkage facilitated π-cation/anion interactions with PHE463, rationalizing its antifungal specificity. Structure-activity relationships (SAR) underscored the critical roles of electron-deficient pyrimidine cores for antibacterial activity and sulfur moieties for antifungal action. These findings position thiopental-pyrimidine hybrids as versatile leads for combating microbial resistance, with 3c representing a particularly promising antifungal candidate. Our integrated synthetic, biological, and computational approach provides a blueprint for optimizing these scaffolds for clinical translation.

A new series of structurally diverse indole–1,2,4-triazole derivatives was designed and synthesized through a thiolated triazole intermediate derived from indole-3-propionic acid. The final compounds, including S-acetamide, bis-indolyl, triazolothiadiazole, and triazolothiadiazine analogues (3–8), were confirmed by NMR, IR, MS, and elemental analysis. Their cytotoxicity was tested against breast (MCF-7), colon (HCT-116), and liver (HepG2) cancer cell lines, alongside normal BJ-1 fibroblasts, using the LDH assay. Several compounds, especially 3, 6b, 7a, 7c, and 8a,b showed potent and selective antiproliferative effects on MCF-7 and HCT-116 cells with IC50 values between 2.3 and 3.0 μM, outperforming doxorubicin nearly twofold under the same conditions. Mechanistic studies revealed a significant decrease in phosphorylated ERK (pERK) protein levels in MCF-7 cells, with compound 3b showing the strongest inhibition (3.499 ± 0.21 pg/mL), consistent with its IC50 (2.3 μg/mL). Molecular docking supported the strong binding affinity of 3b within the ERK active site (−9.0 kcal/mol), involving hydrogen bonding and hydrophobic interactions. In silico ADMET predictions confirmed favorable drug-likeness, oral bioavailability, and pharmacokinetic safety for this compound. Overall, compound 3b emerges as a promising lead for ERK-targeted anticancer drug development, supported by combined synthetic, biological, and computational evidence.

The investigation of 1,2,4-triazole-chalcone has sparked immense interest due to their promising biological activities. These compounds, labeled 10C-10S, were synthesized and characterized by Jinjing et al., specifically focusing on their potential applications in biological settings, particularly their antiproliferative properties. Strategic exploration by computational chemistry techniques such as DFT calculations, molecular docking, and molecular dynamics with empirical findings proved pivotal in unraveling the multifaceted properties of these organic molecules. Additionally, molecular docking studies were conducted to elucidate the antiproliferative effects and analyze the potential binding modes of the compounds with specific amino acid residues in proteins. Rigorous comparisons between theoretical and experimental results yielded comprehensive insights into the properties of these compounds. We chose two molecules, C (the most active) and E (the least active), which have affinities of -7.689 and -7.526 kcal/mol, respectively, to test how stable they are with the EGFR receptor (PDB entry code: 6Z4B). Molecular dynamics simulations over 100 ns revealed more stable energies, with ΔG_Bind = -25.135 Kcal/mol and ΔG_Bind_vdW = -30.644 Kcal/mol.

The development of effective insecticides is crucial for sustainable agriculture. This research focuses on a series of pyridine derivatives (3–9) that were prepared and evaluated for their agricultural bioefficacy as potential insecticides against cowpea aphid, Aphis craccivora Koch (Homoptera: Aphididae). The results demonstrate significant variations in bioefficacy among the tested compounds. Toxicity index analysis revealed the following order of insecticidal activity: 8>4>6>3>5>7>9, highlighting compound 8 as the most potent. Furthermore, potential binding interactions were elucidated through molecular docking studies between these compounds and relevant insect target proteins. So, the observed bioactivity trends were rationalized with the use of the docking data, which offered useful information on the binding affinities and molecular interactions. AChE, or acetylcholine esterase (PDB ID: 2ACE), has been docked against the seven synthetic molecules (3–9). Interestingly, compounds (2-(pyridin-2-ylthio)acetonitrile; 8), (2-(pyridin-2-ylthio)acetic acid; 6), and (ethyl 2-(pyridin-2-ylthio)acetate; 4) had the highest binding affinity, with respective docking scores (S) of -7.51, -7.45, and -7.12 kcal/mol, while compounds (thieno[2,3-b]pyridine derivatives; 7 and 9) had the lowest binding affinity (S=-6.52 and -6.73 kcal/mol, respectively). According to protein-ligand docking configurations, these compounds exhibited a range of binding interactions inside the 2ACE active site. Hence, this study contributes to the development of new pyridine-based insecticides for sustainable pest management in agricultural applications.

The Diels-Alder cycloaddition of cyclopentadienone derivative 3-methyl-5,6,7,8-tetrahydroazulen-1(4H)-one with a series of maleimide derivatives is studied using Molecular Electron Density Theory at the B3LYP/6-311++G(d,p) computational level. Conceptual Density Functional Theory analysis predicts low reaction polarity, which is confirmed by global electron density transfer analysis at the transition structures. Topological analysis reveals the electron distribution and evolution of multiple covalent and non-covalent interactions at the transition structures. The results indicate that these Diels-Alder reactions follow an asynchronous one-step mechanism under kinetic control, favouring the endo product formation. Bonding Evolution Theory shows that the reaction mechanism can further be decomposed into five distinct bonding evolution phases. In addition, a molecular docking study is conducted to assess the antimicrobial potential of the reaction products against Escherichia coli and Staphylococcus aureus. An evaluation of the results of binding affinity and molecular interactions concludes that the products are viable as antimicrobial agents.

The present paper elicits the studies on synthesis and potential pharmacological applications of pyrazolo-oxazole heterocyclic scaffolds. The synthesized compounds were characterized by different spectroanalytical tools including ¹H NMR, ¹³C NMR, and FTIR techniques, followed by molecular docking-based biological interaction studies. Synthesized pyrazolo-oxazoles (8a–f) were docked against the heme-binding protein of P. gingivalis, an oral pathogen, responsible for a number of diseases. Among the synthesized heterocycles, compounds 8e and 8f showed better docking scores compared to the marketed drugs and thus are of great interest as lead compounds in developing treatment profiling to combat P. gingivalis-borne diseases.

A series of new benzimidazole phosphonate derivatives was obtained via nucleophilic addition of triethyl phosphite to the imine of the imidazole subgroup under solvent-free conditions. Structures of the formed products were confirmed using spectroscopic data (ATR-FTIR, ¹H-NMR, ¹³C-NMR, and MS). The antimicrobial profiles of the synthesized compounds were examined, and promising activities against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans were revealed, showing significant inhibition zone diameters ranging from 13 to 17 mm. Alongside these experimental findings, in silico investigations were conducted using ADMET characteristics, which showed a positive pharmacokinetic profile and provided valuable information on potential interactions with target molecules. Besides, docking studies against tested microorganisms revealed further insights on the compounds’ binding interactions with the active sites. Finally, DFT analysis was performed to shed light on the synthesis of novel molecules.