Ishik University

A new symmetrical azine, 1,2-bis(1-(5-bromothiophen-2-yl)ethylidene)hydrazine (5BEH), was synthesized via a simple ionic-liquid-assisted protocol and fully characterized using FT-IR, NMR, and single-crystal X-ray diffraction. The compound crystallizes in the monoclinic P21/c space group, and Hirshfeld surface analysis revealed that the Br & ctdot;H/H & ctdot;Br and S & ctdot;H/H & ctdot;S interactions dominated the supramolecular packing, supported by additional dispersion-driven H & ctdot;H contacts. Density functional theory (DFT) calculations at the B3LYP/6311++G(d,p) level reproduced the experimental geometry and vibrational features with high accuracy. Frontier molecular orbital and NBO analyses showed a moderately narrow HOMO-LUMO gap (3.58 eV), strong pi ->pi* and LP ->pi* charge-transfer pathways, and a bipolar electrostatic profile with electrophilic N-N/C=N regions and nucleophilic Br/S sites. Docking studies against meningitis-associated targets (4CVD and 4UMB) indicated that 5BEH binds more favourably than ceftriaxone, although with a weak absolute inhibitory affinity. ADME predictions further demonstrated good intestinal absorption, BBB penetration, low toxicity, and no hERG or carcinogenic risk, with CYP2D6 inhibition being a noted metabolic consideration. Overall, the structural, electronic, and in silico findings identify 5BEH as a stable, electronically versatile azine scaffold with in silico indicative potential for medicinal and materials-oriented applications.

The metallic complexes with the pharmaceutical drugs have improved the mechanical strength, site action, enhanced stability and biological activities. In this research work, the controlled release from PVA/AgO nanobiocomposite hydrogel and biological potential of oxytetracycline (OTC) and Cu-OTC complex were compared. The OTC which is an antimicrobial class of tetracycline was altered chemically with the coordination complex of the copper ion. The OTC complex with copper (II) using copper chloride and OTC in one-pot synthesis was obtained to explore the biological activities and release kinetics. The OTC methanolic solution was mixed in copper chloride methanolic solution and then it was refluxed for three hours to get the fine crystals of Cu-OTC complex. The prepared complex was characterized using various techniques as measurement of melting points, UV-Vis spectrophotometer, FTIR spectroscopy, Surface-Enhanced Raman spectroscopy (SERS) along Principal Component analysis (PCA), Thermogravimetric analysis (TGA), Differential Scanning Calorimetry (DSC), NMR (1H 13C), SEM, EDX and X-ray Diffraction (XRD). The prepared complex and OTC were loaded on PVA/AgO hydrogel and controlled release in phosphate buffer solution of pH 7.4 at 37 °C for 33 h with the interval gap of 3 h was evaluated by using UV-Vis spectrophotometer. The Higuchi and Korsmeyer-Peppas models were employed to study the release kinetics. The antibacterial activity, MIC, and MBC against E. coli and S. aureus bacteria, hemolytic analysis and cytotoxicity against human colon cancer cells (SW480) were also performed to analyze the biological potential of the prepared complex. The molecular docking was also performed to compare the antibacterial and cytotoxicity of OTC and Cu-OTC complex. The stoichiometry determined by Job’s method proved the 1:1 Cu-OTC complex which is consistent with spectroscopic results. The Cu-OTC complex was found to have better antibacterial properties than free OTC based on increased yielding of broader zones of inhibition and reduced MIC/MBC. Diffusion controlled kinetics Studies of controlled release showed sustained release behavior at the PVA/AgO hydrogel. The cytotoxicity analysis showed that the Cu-OTC complex inhibited the growth of SW480 cells more than OTC did without causing significant hemocompatibility loss.

The urokinase plasminogen activator receptor (uPAR) is crucial in processes such as tumor invasion, epithelial–mesenchymal transition, and the metastatic spread of aggressive cancers, including triple-negative breast cancer (MDA-MB-231) and skin cancer (A431). Due to its overexpression and key role in regulating extracellular matrix degradation and cell migration, uPAR stands out as a promising but underutilized therapeutic target. This research combines computational modeling with experimental validation to discover new small-molecule inhibitors of uPAR. A comprehensive QSAR model was developed utilizing 816 structurally diverse uPAR antagonists, resulting in high internal predictivity (R² = 0.84) and external validation accuracy (R²_ext = 0.8014). Key molecular descriptors that influence inhibition, such as com_Nminus_2A, lipo_S_1Ac, fHC3B, and fdonringC7A, have been identified as critical factors in determining electrostatic and steric complementarity. The virtual screening of the ChemDiv database using QSAR methods identified two lead candidates: D685-0061 and C878-1660. Molecular docking analysis demonstrated that C878-1660 interacts with uPAR through advantageous hydrophobic and hydrogen-bond interactions, while D685-0061 displayed relatively weaker binding affinity. The ligand, C878-1660 formed a stable complex (RMSD ~ 1.5 Å over 500 ns), whereas D685-0061 showed higher flexibility (RMSD ~ 2.7 Å). The cytotoxic effects of both ligands were quantified using in vitro MTT assays. D685-0061 demonstrated a higher potency in MDA-MB-231 cells, with an IC₅₀ of 21.34 µM, in contrast to C878-1660, which had an IC₅₀ of 81.82 µM. Conversely, C878-1660 showed greater effectiveness in A431 cells, exhibiting an IC₅₀ of 18.93 µM compared to D685-0061’s IC₅₀ of 28.34 µM. The observed apoptotic morphology was consistent with a dose-dependent relationship, supporting these findings. This study presents a thorough computational-experimental pipeline that identifies two promising lead molecules targeting uPAR and provides mechanistic insights into their binding and cytotoxic profiles. The gathered evidence substantiates the need for further optimization and progression toward preclinical evaluation for uPAR-driven cancers.

Since cisplatin was discovered and used as an anti-cancer agent in clinical settings, research into cancer treatments has revealed a number of possible drugs based on metal-containing scaffolds. This has produced a large number of metallodrugs suitable for use in medicine. The roles and mechanisms of action of these metallodrugs are more diverse than those of pure organic compounds. Since they demonstrated efficacy against numerous cancer cell lines, metallodrugs based on osmium are among the most researched and produced substitutes for platinum-based anti-cancer drugs. The metal-based drugs are a new, well-developed type of drug in anticancer therapy with specific mechanisms of action that are much different from the organic chemical drugs used in chemotherapy. They have the potential to disrupt cellular processes necessary for the survival and growth of cancer cells since they are able to interact with a variety of biological targets such as DNA, proteins, and enzymes. This review article focuses on the role of Os-complexes in cancer treatment, their mechanism of action, challenges, and future perspectives of Os-complexes in cancer therapy.

Clayey soils undergo considerable volumetric changes with moisture variation, ranging from shrinkage to swelling, thereby posing serious challenges for civil engineering projects. Therefore, stabilizing clayey soils is crucial, particularly for road construction. This study investigates the effects of recycled ceramic waste powder (CWP) on the geotechnical behavior of high-plasticity clay (CH) to enhance soil strength and reduce environmental impacts. The research evaluates clay soil properties mixed with CWP at varying percentages (0%, 6%, 12%, 18%, and 24% by dry weight of the soil samples). Laboratory tests were conducted on untreated and CWP-stabilized soils, including Atterberg limits, free swelling (FS), standard Proctor compaction, unconfined compressive strength (UCS), and California bearing ratio (CBR). The results indicate that with increasing percentages of CWP, the index properties, FS, optimum moisture content (OMC), energy absorption capacity, and required pavement thickness decreased up to 24% CWP content. Meanwhile, maximum dry density (MDD), UCS, CBR, and resilient modulus increased up to 12% CWP content, beyond which these properties began to decline. At this optimum CWP content of 12%, MDD increased by 13.01% compared with the untreated CH soil, UCS improved by 39.7%, and the soaked CBR rose from 3% (CH soil) to 19%, representing an approximate 533.3% increase. Microstructure analyses confirmed that 12% CWP treatment enhanced the chemical and microstructural stability of the soil, contributing to the observed improvements in strength. Polynomial regression models demonstrated strong predictive capabilities (R2 = 0.8815–0.9975), capturing non-linear trends and optimizing CWP content for soil performance. Notably, the correlations between UCS and CBR (R2 = 0.993) validated the statistical framework for strength estimations. These findings indicate that incorporating CWP improves soil compaction behavior, reduces swell potential, and significantly enhances strength. Accordingly, CWP may serve as a promising low-cost and environmentally friendly stabilizing additive for improving clayey soils in foundation and subgrade applications.