Fouzia Perveen

Background/Objectives: Indoles and benzimidazoles are important nitrogen-containing heterocyclic scaffolds and are a cornerstone of synthetic drugs. In this study, benzamides of 2-aminophenylindoles and 2-aminophenylbenzimidazoles were synthesized and evaluated for their potential. Further, they were also subjected to computational studies for their ADMET profiling and binding with target proteins. Methods: The synthesized compounds were characterized by ATR-FTIR, 1H NMR, 13C NMR and electrospray ionization mass spectroscopy (ESI-MS). They were screened for their in vitro antibacterial activity by the Microplate Alamar Blue Assay (MABA) and for their anticancer potential by the MTT assay against the HeLa, PC3 and 3T3 cell lines. Further, the compounds were assessed for their ADMET profiles by the Deep-PK platform, and binding with selected kinases was assessed by AutoDock Vina v1.2.7, followed by MD simulations in GROMACS. Density functional theory (DFT) calculations were also performed to investigate the electronic properties of the synthesized compounds. Results: All synthesized compounds were inactive in antibacterial assays and mildly active against cancer cells. N-[4-(1H-benzimidazol-2-yl-phenyl]benzamide (4-APB-B) exhibited good activity against the HeLa cell line (IC50: 5.48 ± 0.01 µM) while showing very low cytotoxicity against the 3T3 cell line (selectivity index: 10.7), against which doxorubicin was highly active, indicating selectivity towards specific cancer cells. Docking studies indicated favorable binding affinities towards the selected kinase targets. Further, ligands with the best binding affinities in docking studies were subjected to MD simulations of 100 ns, and DFT studies were also performed to assess the electronic properties of the synthesized compounds. Conclusions: Our study provides a pathway for the synthesis of 2-phenylbenzimidazoles and 2-phenylindoles and demonstrates that the synthetic compound 4-APB-B possesses remarkable selective cytotoxic activity and can serve as a lead molecule for further development into a successful anticancer agent.

Introduction: Sorafenib remains the only approved treatment for advanced hepatocellular carcinoma (HCC), yet its clinical use is hindered by toxicity and the emergence of drug resistance. Sorafenib’s anticancer effects are largely attributed to its inhibition of multiple kinases, including c-Raf, a key player in the Ras–Raf–MEK–ERK signaling cascade that promotes cell growth and survival. Given the critical role of c-Raf in tumor progression, targeting this kinase offers a promising strategy for improving therapeutic outcomes. Developing new analogs with stronger c-Raf inhibition, better pharmacokinetics, and reduced side effects could help address the current limitations of sorafenib. Objectives: This study aimed to design novel sorafenib analogs with enhanced binding affinity and favorable pharmacokinetic profiles, specifically targeting the c-Raf kinase to increase therapeutic efficacy against HCC. By using a fragment replacement approach combined with computational methods, the goal was to identify candidates capable of forming stronger, more stable interactions with c-Raf, potentially overcoming resistance linked to sorafenib treatment. Methods: A total of 84 sorafenib analogs (A1–A84) were generated by modifying key functional groups, including the 2-picolinamide and substituted phenyl moieties known to influence kinase binding and anticancer activity. These analogs were evaluated through chemoinformatics and pharmacokinetic screening to assess their drug-likeness and safety. Molecular docking was performed to estimate their binding affinity toward c-Raf. Six top-performing analogs (A2, A6, A9, A20, A22, A63) were selected for further analysis. To evaluate their dynamic behavior, 100[ ]ns all-atom molecular dynamics simulations were conducted, followed by Molecular Mechanics Poisson–Boltzmann Surface Area (MM-PBSA) calculations to determine binding free energies. Principal component analysis (PCA) was carried out to explore key motion patterns within the protein–ligand complexes. Results: Molecular docking showed that the selected analogs exhibited stronger binding affinities (−11.6 to −10.9[ ]kcal/mol) compared to sorafenib (−9.3[ ]kcal/mol) and regorafenib (−9.5[ ]kcal/mol). Molecular dynamics simulations substantiated the docking results. MM-PBSA results revealed that at 100[ ]ns, the binding free energy for the c-Raf–sorafenib complex was 86.751[ ]kJ/mol, while the c-Raf complexes with A2, A6, A9, A20, A22, and A63 demonstrated significantly lower free energies of −129.114, −135.637, −136.242, −127.178, −94.25, and −123.176[ ]kJ/mol, respectively, indicating stronger and more stable binding. PCA further confirmed the stability and favorable dynamic profiles of these analogs trajectory with c-Raf. Discussion: The improved binding affinities and lower free energies of the top analogs indicate that specific structural changes to sorafenib can enhance its effectiveness against c-Raf. Molecular dynamics and MM-PBSA results suggest the stability and strength of these interactions, particularly for A2, A6, and A9. Conclusion: This study identified six promising sorafenib analogs with improved binding affinity, favorable pharmacokinetic characteristics, and stable interactions with c-Raf. By focusing on c-Raf inhibition, the combined use of computational modeling, molecular simulations and mmPBSA analysis provided valuable insights for drug design. Among the candidates, A2, A6, and A9 emerged as promising drug candidates for further development, supporting the potential of targeting c-Raf to enhance therapeutic strategies against HCC.

MXenes, two-dimensional materials, have emerged as leading candidates for next-generation energy storage due to their exceptional metallic conductivity and tunable surface chemistry.

MXenes, two-dimensional transition metal carbides/nitrides, have gained substantial interest owing to their distinctive properties. This study utilizes density functional theory (DFT) calculations to study the electronic, magnetic, and thermoelectric properties of pristine, molybdenum (Mo), and Te-doped Nb₃C₂ monolayer MXenes. Both doped structures exhibit metallic characteristics with indirect band gaps, as revealed by band structure and density of states (DOS) analysis. This fulfills a crucial requirement for electrode applications in lithium-ion batteries (LIBs). Pristine Nb₃C₂ displays diamagnetic, while Mo doping induces ferromagnetism and Te doping leads to ferrimagnetism behavior. Notably, doping significantly impacts electronic and thermoelectric properties, Seebeck coefficient, electrical conductivity, and thermal conductivity, which demonstrably depend on the chosen structure. Te-doped Nb₃C₂ consistently exhibits a larger bandgap, less Seebeck coefficient, and lower thermal conductivity compared to Mo-doped Nb₃C₂ attributed to a narrow bandgap, exceptionally high Seebeck coefficient, and high thermal and electrical conductivity. Additionally, positive open-circuit voltage (OCV) values suggest favorable lithium-ion intercalation for all materials. Theoretical capacities of 592, 745, and 668 mAh/g are computed for pristine, Mo-doped, and Te-doped Nb₃C₂, respectively, comparable to reported values for pristine V₃C₂ (606.42 mAh/g). These results suggest that Mo- and Te-doped Nb₃C₂ MXenes exhibit potential as anode materials for LIBs due to their improved electronic conductivity, reduced operating voltage, and comparable theoretical lithium storage capacity.

Introduction: Glioblastoma is a grade IV solid brain tumor and has a 15-month survival rate even after treatment. Glioblastoma development is heavily influenced by retinoblastoma protein (pRB) pathway changes. The blood–brain barrier, drug resistance, and severe toxicity of Temozolamide are key obstacles in treating glioblastoma. Innovative treatments targeting the pRB pathway with efficient delivery vehicles are required to treat glioblastoma.Methods: For this purpose, a library of 691 plant extracts previously tested in vitro for anti-cancerous, anti inflammatory, and anti-proliferative characteristics was created after thorough literature investigations. Compounds were docked against pRB pathway protein ligands using molecular operating environment and chimera. Their nuclear structure and drug-like properties were predicted through Lipinski rule and density functional theory analysis. Physio-chemical characterizations of naked and drug-encapsulated SLNPs assessed size, stability, entrapment efficiency, and drug release rate. Anti-cancer potential of drug and drug- loaded SLNPs was evaluated using U87, U251, and HEK cell lines. Formulations were tested for cancer cell metastatic potential using cell migration assays.Results: Silymarin (Sil) was identified as the most potent compound against CDK4, which was then encapsulated in stearic acid solid lipid nanoparticles (SLNP-Sil). Sil showed decreased cell viability 72 h after treatment against both U87 and U251 cell lines but had negligible cytotoxic effect on HEK-293. IC50 value of Sil was 155.14 µM for U87 and 195.93 µM for U251. Sil and SLNP-Sil effectively inhibited U87 and U251 cell migration 24 h after treatment.Discussion: Our results indicated that Sil and SLNP-Sil are promising therapeutic approaches against glioblastoma and merit in vivo experimental verification using orthotropic xenograft mouse models against glioblastoma.

The purpose of this study is to examine the possibility of GO to be used as an adsorbent for five novel potentially hazardous azo-dyes for their removal from aqueous solution. Adsorption characteristics of GO for azo-dyes removal were investigated by means of experimental and computational DFT as well as Monte Carlo approaches. Experimental studies include the effect of adsorbent dose, contact time, and initial concentration, while computational investigation involves DFT and Monte Carlo (MC) simulations. Through DFT studies geometric, electronic, and thermodynamic parameters were explored and possible mechanism of interactions and adsorption energies by predicted through MC by searching lowest possible adsorption complexes. Experimental data were evaluated by Langmuir models in order to describe the equilibrium isotherms. Equilibrium data fitted well to the Langmuir model. Thermodynamic parameters i.e., free energy change, enthalpy change, and entropy change revealed that the removal of azo-dyes by adsorption on the surface of GO molecular sieves was spontaneous. Nature of the process was found to be physiosorption involving non-covalent interaction. The study unveiled that GO can be used as an efficient adsorbent material for the adsorption of azo-dyes from aqueous solution.

Additive manufacturing (AM), commonly referred to as 3D printing, has revolutionized the manufacturing landscape by enabling the intricate layer-by-layer construction of three-dimensional objects. In contrast to traditional methods relying on molds and tools, AM provides the flexibility to fabricate diverse components directly from digital models without the need for physical alterations to machinery. Four-dimensional printing is a revolutionary extension of 3D printing that introduces the dimension of time, enabling dynamic transformations in printed structures over predetermined periods. This comprehensive review focuses on polymeric materials in 3D printing, exploring their versatile processing capabilities, environmental adaptability, and applications across thermoplastics, thermosetting materials, elastomers, polymer composites, shape memory polymers (SMPs), including liquid crystal elastomer (LCE), and self-healing polymers for 4D printing. This review also examines recent advancements in microvascular and encapsulation self-healing mechanisms, explores the potential of supramolecular polymers, and highlights the latest progress in hybrid printing using polymer–metal and polymer–ceramic composites. Finally, this paper offers insights into potential challenges faced in the additive manufacturing of polymer composites and suggests avenues for future research in this dynamic and rapidly evolving field.

Context Adsorption of 1 and 2 H₂O molecules for hydrogen production and storage on the surface of pristine, carbamic acid and 2-amino 3-acetylpyridine functionalized SWCNTs with the dimensionality of (2, 4), (5, 5), and (6, 0) at various positions, i.e., center and edges were investigated by using computational DFT calculations. Adsorption energies and structural and electronic parameters were determined for pristine and functionalized SWCNTs with four different H₂O orientations. Functionalization of 2-amino 3-acetylpyridine resulted in more favorable adsorption energies for 1 and 2 H₂O molecules splitting as compared to spitting on pristine and carbamic acid functionalized SWCNT. Calculated adsorption constant, Kad confirmed greater binding interactions of functionalized SWCNTs with 1 and 2 H₂O molecules as compared to pristine SWCNT. Isosurface for the adsorption of 1 and 2 H₂O molecules on pristine and functionalized SWCNTs elaborated altered electrophilic and nucleophilic character. Effect of H₂O concentration was monitored to determine hydrogen storage capacity which was found to be 7.17 wt.% for thirty molecules. An important finding of study is production of Stone-Wales (SW) defect upon H₂O adsorption leading to increase in hydrogen production and its storage capacity. The functionalization of topological defected SWCNTs provides distinctive applications of CNTs for gas storage purposes.t: Methods In the current study, First Principal Density Functional Theory (DFT) calculations were carried which provides greater computational efficiency as compared to many traditional quantum mechanical methods. SCME: ADF (2018) modeling suite software with in framework of DFT approach using exchange correlation (XC) LDA-GGA (Generalized Gradient Approximation) with PBE (Perdew, Burke and Ernzerhof) functional and DZ (Double beta) basis set was employed to investigate structural, energetic and electronic aspects of adsorption on the surface of pristine, carbamic acid and 2-amino 3-acetly pyridine functionalized SWCNTs. (2, 4), (5, 5) and (6, 0) SWCNTs were designed using Avogadro’s software and were imported to SCM: ADF graphical interface and were optimized as adsorbent. Single point energy (SPE), geometry optimization and high accuracy frequency calculations were performed to determine energetic, electronic and thermodynamic characteristics and feasibility of adsorption using XC of GGA-PBE functional & DZ basis set.

Bis-acyl-thiourea derivatives, namely N,N’-(((4-nitro-1,2-phenylene)bis(azanediyl)) bis(carbonothioyl))bis(2,4-dichlorobenzamide) (UP-1), N,N’-(((4-nitro-1,2-phenylene) bis(azanediyl))bis(carbonothioyl))diheptanamide (UP-2), and N,N’-(((4-nitro-1,2-phenylene)bis(azanediyl))bis(carbonothioyl))dibutannamide (UP-3), were synthesized in two steps. The structural characterization of the derivatives was carried out by FTIR, ¹H-NMR, and ¹³C-NMR, and then their DNA binding, anti-urease, and anticancer activities were explored. Both theoretical and experimental results, as obtained by density functional theory, molecular docking, UV-visible spectroscopy, fluorescence (Flu-)spectroscopy, cyclic voltammetry (CV), and viscometry, pointed towards compounds’ interactions with DNA. However, the values of binding constant (K_b), binding site size (n), and negative Gibbs free energy change (ΔG) (as evaluated by docking, UV-vis, Flu-, and CV) indicated that all the derivatives exhibited binding interactions with the DNA in the order UP-3 > UP-2 > UP-1. The experimental findings from spectral and electrochemical analysis complemented each other and supported the theoretical analysis. The lower diffusion coefficient (D_o) values, as obtained from CV responses of each compound after DNA addition at various scan rates, further confirmed the formation of a bulky compound–DNA complex that caused slow diffusion. The mixed binding mode of interaction as seen in docking was further verified by changes in DNA viscosity with varying compound concentrations. All compounds showed strong anti-urease activity, whereas UP-1 was found to have comparatively better inhibitory efficiency, with an IC₅₀ value of 1.55 ± 0.0288 µM. The dose-dependent cytotoxicity of the synthesized derivatives against glioblastoma MG-U87 cells (a human brain cancer cell line) followed by HEK-293 cells (a normal human embryonic kidney cell line) indicated that UP-1 and UP-3 have greater cytotoxicity against both cancerous and healthy cell lines at 400 µM. However, dose-dependent responses of UP-2 showed cytotoxicity against cancerous cells, while it showed no cytotoxicity on the healthy cell line at a low concentration range of 40–120 µM.