In this work, the synthesis of 6,6'-([2,2'-bi(1,3,4-oxadiazole)]-5,5'-diyl)bis(3-chloroaniline) (6a) and 5,5'-([2,2'-bi(1,3,4-oxadiazole)]-5,5'-diyl)bis(benzene-1,3-diamine) (6b) was carried out and characterized by spectral data from 1H NMR, ¹³C NMR, IR and mass spectrometry. The optical properties of these compounds were studied, in particular the evolution of reflectance, absorption and band gap energy, and a scanning electron microscopy (SEM) analysis was performed. A comparative in-silico study combining DFT-based reactivity analysis, ADMET prediction, and molecular docking were employed for compounds 6a and 6b. Both exhibited distinct reactivity profiles and strong binding affinities toward DNA Gyrase B (7C7N) and the DNA-ruthenium complex (4E7Y), highlighting their potential as antibacterial agents, as well their potential use in photovoltaic application and for near infrared light shielding basing on the optical results.

This study presents the synthesis and characterization of the novel compound 6,6'-(1,3,4-oxadiazole-2,5-diyl)bis(3-chloroaniline), using 1H NMR, 13C NMR, mass spectrometry and FTIR-ATR infrared spectroscopy. Density Functional Theory (DFT) calculations at the B3LYP/6-311G (d,p) level, were employed to optimize the molecular geometry and evaluate electronic properties. Frontier molecular orbital, molecular electrostatic potential, Parr function, and electron localization function analyses revealed an ambiphilic character, with electrophilic sites localized on the oxadiazole core and nucleophilic regions on the chloroaniline moieties. Molecular docking demonstrated high binding affinities toward Topoisomerase IV, Tubulin, and CDK2, surpassing standard ligands and indicating potential antibacterial and anticancer activities. ADME/Toxicity predictions suggested good pharmacokinetic behavior and low toxicity. Monte Carlo and molecular dynamics simulations confirmed strong and stable adsorption of the novel compound OBA on the Fe (110) surface, supporting its efficiency as a corrosion inhibitor.

The reactions between 2,3-dimethylbutadiene and six azodicarbonyl derivatives give the aromatic α-amino ketone family which presents a great interest in chemical synthesis and especially in polymerization reactions. This reaction was studied using the Molecular Electron Density Theory. The reaction pathways were established using the Intrinsic Reaction Coordinate (IRC) method and confirmed through topological analysis of the Electron Localization Function (ELF). The substituent effect was discussed from the CDFT and GEDT calculations. The temporary formation of hydrogen bonds at TSs is responsible for the mechanistic aspect and the process asynchronous of new bond formation. Consequently, the reaction proceeds via a non-concerted in two-stages mechanism. Finally, we investigated the potential inhibitory effects of six products against HIV-1-Mpro through molecular docking calculations. Then, their medicinal potential and physicochemical properties were scrutinized, employing the SwissADME server, unveiling their non-toxic characteristics and positioning them as promising contenders for drug development.

This study explores the mechanism and solvent effects of the (3+2) cycloaddition between N-(4-(prop-2-yn-1-yloxy)phenyl)-1-(pyridin-2-yl)methanimine and 4-azido-7-chloroquinoline, yielding quinoline–triazole hybrids. DFT/B3LYP/6-311G+(d,p) calculations, supported by ELF and NPA analyses, reveal a one-step mechanism favoring product P1 both kinetically and thermodynamically. Non-covalent interaction (NCI) analysis indicates that TS1 is stabilized by hydrogen-bonding and van der Waals interactions. ADMET screening showed that all cycloadducts are non-toxic (no AMES mutagenicity or skin sensitization). Molecular docking identified P3 and P4 as the most potent ligands for Plasmodium falciparum kinases 5E16 and 5DYK, respectively, with stronger binding affinities than chloroquine. Molecular dynamics simulations further confirmed the structural stability of the P3–5E16 and P4–5DYK complexes, highlighting these derivatives as promising candidates for antimalarial drug development.

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.

Benzimidazole continues to be an intriguing scaffold in recent drug discovery, owing to its broad spectrum of pharmacological effects. In recent years, a variety of its derivatives, which included chalcone imines, hydrazones, and thiosemicarbazones, were actively investigated for their antitumor potential. In the search for new agents capable of treating kidney cancer, an analysis of a small series of 2-substituted benzimidazoles (45) using 3D-QSAR modelling was performed to determine the antiproliferative activities against cancer cell lines A-498. The biological activity was sufficient to establish a meaningful structure–activity relationship, providing a foundation for the design of more potent compounds. The activity-favouring and activity-disfavoring structural regions were clearly revealed using contour maps generated by the models. The CoMSIA/SHD model was one of the best developed, and its high statistical robustness (q2 = 0.751) and predictive power (R2 pred = 0.924) indicated its reliability. We designed five new derivatives of benzimidazole based on the QSAR results, which demonstrated potent inhibitory potential. Molecular docking studies were performed in order to investigate in detail their interaction modes with the aromatic receptor, and stable binding conformations at the active site have been found. The in silico pharmacokinetic studies suggested that these compounds have a favourable ADMET and bioavailability profile, reinforcing their suitability for in vitro testing. Two leads, L15 and L22, with better PKs properties and high-predicted activities, were subjected to a 100-ns MD simulation in complex with the aromatase target to investigate their stability. We also conducted a retrosynthetic analysis for L15 and L22, suggesting potential synthetic routes for experimental validation. Overall, these findings suggest that benzimidazole analogues could be promising candidates for treating RCC and possibly for blocking aromatase.

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.

This study examines the reactivity of an intramolecular cyclization process involving benzastatin, a molecule derived from Streptomyces nitrosporeus, using density functional theory (DFT) with the B3LYP functional and the 6-311G(d,p) basis set. Parr indices, calculated by natural bond orbital (NBO) analysis, provide insight into the reactivity and chemical behavior of the system. In addition, the electron localization function (ELF) is used to analyze bond formation during the process. A molecular docking study highlights the pharmacological potential of benzastatin-derived alkaloids against Plasmodium falciparum, the malaria parasite, by targeting the key enzymes falcipain-2 and falcipain-3. The study elucidates the key interactions and binding affinities between the reaction products involved and these enzymes, supported by molecular dynamics simulations to study the stability of the ligand-protein complex over 50 ns. ADMET predictions suggest favorable pharmacokinetic profiles and low toxicity for the compounds, underlining their potential as antimalarial drug candidates.

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.