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关键词： Biological potential   Metal complex   Pyrazole   Schiff base   Thiopyrazoline  

摘要： The present research reports the successful synthesis of N,N-bis(4-acyl-3-methyl-1-phenyl-2-pyrazoline-5-thione)-Ethane-1,2-diamine (AMPPT-END) ligand and its metal complex, achieved despite significant challenges associated with ligand formation and stability. Identification of the structural tautomeric forms (N–H, C–H, S–H) of the ligand constituted a major challenge. The possible tautomeric structures were assessed based on their electronic stability and subsequently confirmed using instrumental methods of analysis (elemental, spectroscopic (FT-IR, ¹H- and ¹³CNMR ), and mass spectrometry) and theoretical calculation (density functional theory analysis). Careful optimization of reaction conditions enabled the isolation of the ligand and subsequent complexation with the metal ions (Mn²⁺and Ni²⁺). The obtained metal complexes Mn-AMPPT-END and Ni-AMPPT-END were further characterized to establish structural confirmation and investigate their inherent biological potential. The study demonstrates that the ligand possesses intrinsic thermodynamic and electronic stability along with significant biological activity, which is preserved upon metal coordination. The comparable biological activity in the initial assay, complexation offers additional advantages such as improved stability, solubility, and potential for targeted delivery.

关键词： Ce3+sensor   Chemosensor   Click chemistry   DFT analysis   Real time analysis  

摘要： A new protocatechualdehyde-tethered 1,2,3-triazole fluorescent probe (PCT) was synthesized via Cu(I)-catalyzed ‘click chemistry’ for selective detection of Ce³⁺ ions in acetonitrile–water (4:1, v/v) medium. The structure of PCT was characterized using Fourier Transform Infrared Spectroscopy (FTIR), Nuclear Magnetic Resonance Spectroscopy (¹H & ¹³C NMR), and Gas Chromatography–Mass Spectrometry (GC–MS) analysis. PCT unveiled a selective fluorescence turn-on response toward Ce³⁺ via photoinduced electron transfer (PET) mechanism, with low detection limit of 1.38 × 10⁻⁷ M and binding constant (Kₐ) of 4.03 × 10⁶ M⁻¹. Job’s plot, FTIR spectroscopy and Liquid Chromatography–Mass Spectrometry (LCMS) analysis established 1:1 binding stoichiometry of [PCT-Ce³⁺] complex. Furthermore, density functional theory (DFT) calculations was run using 6-311G++(d,p)/SDD basis set for PCT and [PCT-Ce³⁺] complex that validated it’s formation via the HOMO–LUMO energy gap reduction. PCT was effectively applied for Ce³⁺ ions quantification in real water samples and demonstrated reversible INHIBIT logic gate behavior.

关键词： Antitumor efficacy   Inhibition of autophagy initiation   Small-molecule inhibitor   VCP–UFL1–Beclin1 axis  

摘要： Targeting autophagy initiation represents a promising strategy to disrupt the metabolic resilience of cancer cells. In this study, we identified ATI-1 as a novel small-molecule inhibitor that selectively blocks the early stages of autophagosome formation. Importantly, we discovered that ATI-1-mediated de novo inhibition of autophagy initiation leads to a synergistic surge in cell death under nutrient-deprived conditions, revealing a critical, context-specific vulnerability in autophagy-dependent malignancies. Mechanistically, ATI-1 appears to target valosin-containing protein (VCP/p97) and disrupt its interaction with the UFM1-specific E3 ligase UFL1. This disruption may promote the polyubiquitination and subsequent degradation of Beclin1, thereby contributing to the inhibition of autophagy initiation. Furthermore, ATI-1 demonstrates potent antitumor efficacy in xenograft models with minimal overt toxicity. This work collectively suggests that the VCP–UFL1–Beclin1 axis may represent a potentially targetable node in autophagy regulation, and identifies ATI-1 as a potential small-molecule modulator of this pathway, thereby providing a promising therapeutic lead for cancer treatment.

关键词： Anti-cancer activity   Benzimidazolium–chalcone hybrid salts   Glioblastoma   Molecular dynamics simulation   Structure–activity relationship   TGF-β1 inhibition  

摘要： The transforming growth factor-β (TGF-β) signaling pathway is crucial in promoting tumor growth, enabling tumors to evade immune responses, and contributing to resistance against therapies. As a result, it is a significant target for cancer treatment. However, its full potential remains untapped because selectively inhibiting it without affecting normal cells is challenging. This study reports the design, synthesis, and comprehensive evaluation of novel benzimidazolium-chalcone hybrid salts (3a-3e) that strategically combine two privileged scaffolds with complementary anticancer mechanisms. Following complete structural characterization by Elemental Analysis, FT-IR, and NMR spectroscopy, an integrated experimental and computational workflow supports a three-strategy hypothesis rather than a single lead compound.

关键词： Acute toxicity   Antileishmanial   Cell cycle   Leishmaniasis   Pyrazolo[1,5-c]quinazoline   ROS  

摘要： Leishmaniasis remains a major global health challenge, with current chemo-therapeutics limited by high cost, toxicity, and poor bio-availability. In this study, seventeen new pyrazolo[1,5-c]quinazoline derivatives were designed and synthesized and evaluated for their in vitro antileishmanial activity against Leishmania donovani promastigotes. Compounds 19e and 20k demonstrated superior potency, exhibiting IC₅₀ values lower than miltefosine, while showing minimal cytotoxicity in HeLa and RAW cells (CC₅₀), resulting in favorable selectivity indices. Mechanistic investigations revealed that both compounds significantly elevated intracellular reactive oxygen species (ROS) levels and induced pronounced cell cycle arrest at the sub-G₀/G₁ phase, indicative of programmed-like parasite death. Importantly, in-depth in vivo toxicity profiling in BALB/c mice revealed an excellent safety profile, with no mortality observed up to 20 mg/kg, and only mild, transient histopathological changes noted at the highest tested dose. These findings collectively highlight the potent antileishmanial activity, mechanistic specificity, and favorable safety profile of 19e and 20k. Overall, these pyrazoloquinazoline derivatives represent promising, non-toxic lead candidates for further optimization and development as potential therapeutic agents against visceral leishmaniasis. Their combination of high efficacy, low mammalian cytotoxicity, and predictable mechanistic action underscores their potential to address the unmet need for safer and more effective treatments for leishmaniasis, supporting their advancement toward preclinical evaluation and future clinical development.

关键词： Indirect electrocatalysis   V-substituted polyoxometalates   Cyclization reaction   Pyrrolo[1,2-a]quinoxaline  

摘要：

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  Indirect electrocatalytic synthesis of N-heterocyclic compounds using polyoxometalate catalysts PMo₉V₃.
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  PMo₉V₃ acts as a redox medium, facilitating electron transfer between the electrode and the organic substrate.
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  Synthesized products can be used to prepare bioactive drugs and fluorescent materials via simple reactions.
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  The catalysis mechanism of the indirect electrocatalysis has been intensively discussed and revealed.

关键词： 1-Alkylureas   Glycolurils   Regioselective condensation   Supramolecular organization   X-Ray  

摘要： The two approaches for the preparation of non-symmetrically 1,6- and 1,4-dialkyl-3a,6a-diphenylglycolurils were developed as a result of studying new regioselective reactions of 1-alkyl-5-hydroxy-4,5-diphenyl-1H-imidazole-2(5H)-ones with 1-alkylureas. A selectivity of the formation of 1,6-dialkyl isomers was detected. The 1,6- and 1,4-dialkyl-3а,6а-diphenylglycolurils were isolated in 55–77 % and 11–29 % yields respectively, and characterized by NMR and mass spectroscopy. The mechanism for the formation of 1,6- and 1,4-isomers was proposed. Self-organization of 1-ethyl-6-methyl-3a,6a-diphenylglycoluril and its crystallosolvates with HCOOH, dioxane and a mixture of Py and H₂O (in a 1:1 ratio), 1-butyl-3a,6a-dipheny-4-propylglycoluril, crystallosolvate of 1-ethyl-3a,6a-diphenyl-6-propylglycoluril with MeCN was studied by X-ray diffraction analysis. Based on the analysis of the crystal packing of structures, it was found that the self-organization of studied molecules in crystals of 1,4- and 1,6-disubstituted 3a,6a-diphenylglycolurils demonstrates new examples of supramolecular synthons with $R_2^2\left(8\right)$ motif based on an N-H…O=С hydrogen bond.

关键词： 1,3,4-oxadiazole   ADMET   Anticancer activity   Breast Cancer   Lung cancer  

摘要： Oxadiazoles are five-membered heterocyclic compounds containing nitrogen and oxygen atoms that exhibit diverse pharmacological properties, particularly anticancer activity. This review highlights recent advances in the synthesis, structural modification, and biological evaluation of 1,3,4-oxadiazole derivatives and their hybrids. Numerous studies report potent cytotoxicity of these derivatives against various cancer cell lines, including lung (A549), breast (MCF-7), liver (HepG2), and leukemia, with some compounds surpassing standard drugs such as cisplatin and doxorubicin. Mechanistic investigations reveal that oxadiazole-based molecules act primarily through apoptosis induction, cell cycle arrest, EGFR inhibition, and suppression of metastasis-related enzymes like MMP-9. Computational studies, including molecular docking and ADMET predictions, further validate their strong receptor affinity and favorable pharmacokinetic profiles. Overall, oxadiazole scaffolds represent a privileged class of compounds in anticancer drug design, offering promising leads for the development of selective, potent, and orally bioavailable chemotherapeutic agents.

关键词： 5α-reductase 1   Enzyme inhibition, QSAR modeling   Molecular docking   Quaternary ammonium disinfectants   Surface plasmon resonance  

摘要： Pyridinium quaternary ammonium disinfectants (PYRs) are cationic surfactants widely used as disinfectants, antiseptics, and preservatives since COVID-19 and their potential effects on neurosteroidogenesis remain unknown. This study explored the inhibitions of eleven PYRs (C1-C20) on human and rat 5α-reductase 1 (5α-R1), identifying carbon-chain length dependent inhibition on human enzyme, with a V-shaped pattern, increasing potency from C12 (nadir activity, IC₅₀ = 97.87 μM) to C16 (peak activity, 5.78 μM) and then decreases to C20 (IC₅₀ = 75.93 μM). Enzyme kinetics and SPR (Surface Plasmon Resonance) showed similar high binding of PYRs to human 5α-R1 (C16's KD = 5.24 μM, C18's KD = 19.4 μM). Mechanistic analysis revealed that they exerted mixed/noncompetitive inhibition via binding to the NADPH binding pocket. SAR/QSAR modeling highlighted lipophilicity (LogP), molecular weight, carbon chain length and heavy atoms as key determinants of potency. Notably, these chemicals showed stronger inhibition in human 5α-R1 than in rat, underscoring species-specific pharmacodynamics. Molecular docking confirmed interactions with critical residues in NADPH binding site. Despite exhibiting greater microsomal activity compared to C14 PYR, the efficacy of C16 PYR in intact SF126 cells was diminished relative to C14 PYR due to its limited cellular permeability. The findings provide insights into 5α-R1 inhibition and support the identification of these disinfectants as neurosteroid endocrine disrupting actions.

关键词： Entanglement between remote qubits   Flux-qubit chain   Perfect state transfer   Spin-1/2 chain   Teleportation   XX-hamiltonian  

摘要： We propose the protocol for preparing the maximally entangled Bell state between remote qubits at the ends of the spin-1/2 chain governed by the specially engineered nearest-neighbor XX-Hamiltonian with excited central spin as the initial state. This method does not require including optical constituent in the teleportation protocol and can be implemented in the quantum devices with solid-state architecture for teleporting unknown states or organizing quantum gates between remote qubits. A superconducting flux-qubit chain is an example of such devises.