Search Results (337)

Scoring functions are key elements in docking protocols as they approximate the binding affinity of a ligand (usually a small bioactive molecule) by calculating its interaction energy with a biomacromolecule (usually a protein). In this study, we present a pairwise comparison of scoring functions applying a multi-criterion decision-making approach based on InterCriteria analysis (ICrA). As criteria, the five scoring functions implemented in MOE (Molecular Operating Environment) software were selected, and their performance on a set of protein–ligand complexes from the PDBbind database was compared. The following docking outputs were used: the best docking score, the lowest root mean square deviation (RMSD) between the predicted poses and the co-crystallized ligand, the RMSD between the best docking score pose and the co-crystallized ligand, and the docking score of the pose with the lowest RMSD to the co-crystallized ligand. The impact of ICrA thresholds on the relations between the scoring functions was investigated. A correlation analysis was also performed and juxtaposed with the ICrA. Our results reveal the lowest RMSD as the best-performing docking output and two scoring functions (Alpha HB and London dG) as having the highest comparability. The proposed approach can be applied to any other scoring functions and protein–ligand complexes of interest. Full article

Background/Objectives: Increasing the solid-state landscape of an active pharmaceutical ingredient (API) by generating new crystalline forms (e.g., polymorphs, cyclodextrin (CD) inclusion complexes, co-crystals, and salts) can yield products with significantly enhanced biopharmaceutical properties (especially increased water solubility), thereby improving API delivery and extending its lifetime. The aim of this study was the isolation of new solid forms of the poorly water-soluble non-steroidal anti-inflammatory drug fenbufen (FBF), for which relatively few solid phases have been reported to date. Further motivation for the study is the recent finding that it has potential for repurposing to treat acute pancreatitis. Methods: Interventions for generating new solid forms of FBF included (a) polymorph screening with a variety of solvent media, (b) attempts to form solid inclusion complexes with the native cyclodextrins α-, β-, and γ-CD using various preparative methods, and (c) co-crystallization with a series of coformers to produce co-crystals and/or molecular salts. Results: No new polymorphic forms of FBF were identified, but screening with CDs resulted in isolation and characterization of a new solid inclusion complex with γ-CD. However, co-crystallization of FBF with the water-soluble coformer isonicotinamide yielded two new products, namely a 1:1 co-crystal and an unusual multi-component ionic co-crystal, whose aqueous solubility indicated significant enhancement of FBF solubility. Conclusions: Due to its extremely low water solubility, FBF presented challenges during the study aimed at modifying its crystalline form. However, two new supramolecular forms, a co-crystal and an ionic co-crystal, were isolated, the latter phase having potential for further formulation owing to its significantly enhanced solubility. Full article

This study investigates the influence of specific surface area (SSA) and aluminum hydroxide particle size on sodium aluminate’s purification efficiency in the Bayer process. This research examines how variations in SSA affect the adsorption and incorporation of contaminants such as Cu, Fe, and Zn, as well as the optimal balance between effective purification and excessive Al₂O₃ loss. Different SSA values and purification durations are analyzed to optimize the purification process and determine conditions that maximize impurity removal while maintaining system stability. Additionally, solid residue characterization using X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive spectroscopy (EDS) provides insights into impurity incorporation mechanisms, including isomorphic replacement, surface adsorption, and co-crystallization. This study highlights key process parameters that influence impurity behavior and crystallization dynamics, offering valuable guidance for refining industrial purification strategies and improving aluminum hydroxide quality. Full article

The development of high-performance photocatalysts is vital for combating water pollution and microbial contamination. In this study, visible-light-active Z-scheme heterojunction nanocomposites composed of Co₃O₄ and Nb₂O₅ (CNNC) were synthesized via co-crystallization and subsequent high-pressure annealing to enhance photocatalytic and antimicrobial performance. Structural and optical analyses via XRD, FESEM, TEM, XPS, and PL confirmed the heterojunction formation between porous Co₃O₄ nanoparticles (CONP) and columnar orthorhombic Nb₂O₅ nanoparticles (NONP). The CNNC exhibited significantly improved photocatalytic activity, achieving degradation efficiencies of 95.1% for methylene blue, 72.6% for tetracycline, and 90.0% for Congo red within 150 min. Kinetic studies showed that CNNC’s rate constants were 367% and 466% of those of CONP and NONP, respectively. Moreover, CNNC demonstrated a strong antibacterial effect on Staphylococcus aureus and Escherichia coli with ZOI values of 9.3 mm and 6.8 mm, respectively. Mechanistic analysis revealed that the Z-scheme charge-transfer pathway improved charge separation and reduced electron–hole recombination, contributing to the promoted photocatalytic efficiency. The nanocomposite also showed robust stability and recyclability over five times. These results highlight the promise of CNNC as a bifunctional, visible-light-driven photocatalyst for pollutant decomposition and microbial control. Full article

Objectives: Drug–drug cocrystallization represents a promising approach for the development of novel combination drugs with improved physicochemical and biopharmaceutical properties. The aim of the present research is to prepare novel drug-drug cocrystalline forms of antiepileptic drug carbamazepine (CBZ) with sulfacetamide (SCTM). Methods: The novel CBZ cocrystal methanol solvate and cocrystal hydrate were prepared via solvent evaporation technique and characterized by single crystal X-ray diffraction, differential scanning calorimetry and thermogravimetric analysis. Results: Single-crystal X-ray diffraction and thermal analysis revealed that the multicomponent solids are isostructural, wherein the solvent molecule does not play a structure-forming role. To optimize the synthesis of [CBZ+SCTM+H₂O] (1:1:0.7), the binary and ternary phase diagrams were constructed in acetonitrile at 25 °C. A thorough investigation of the cocrystal hydrate behavior in aqueous solution showed that the pH of the dissolution medium exerted a significant effect on the stability and solubility of [CBZ+SCTM+H₂O] (1:1:0.7). According to the dissolution and diffusion experiments in a buffer solution pH 6.5, the cocrystal hydrate characterized an enhanced dissolution rate and flux of CBZ. Pharmacokinetic studies in rabbits showed that the novel cocrystal hydrate exhibited a comparable bioavailability to the parent CBZ. Conclusions: Overall, this work reports the preparation of a novel CBZ drug-drug cocrystal hydrate, which can be considered as an alternative CBZ solid form for oral usage, possessing additive pharmacological effect. Full article

The cocrystallization of trans-[PtI₂(NCR)₂] (R = NMe₂1, NEt₂2, Ph 3, o-ClC₆H₄4) with iodine and iodoform gave the crystalline adducts 1∙4I₂, 2∙2CHI₃, 3∙2CHI₃, and 4∙4I₂, whose structures were studied by single-crystal X-ray diffractometry (XRD). In the structures, apart from the rather predictable C–H⋯I hydrogen bonds (HBs) and I–I⋯I or C–I⋯I halogen bonds (XBs) with the iodide ligands, we identified bifurcated I–I⋯(I–Pt) and C–I⋯(I–Pt) metal-involving XBs, where the platinum center and iodide ligands function as simultaneous XB acceptors toward σ-holes of I atoms in I₂ or CHI₃. Appropriate density functional theory (DFT) calculations (PBE-D3/jorge-DZP-DKH with plane waves in the GAPW method) performed with periodic boundary conditions confirmed the existence of the bifurcated metal-involving I–I⋯(I–Pt) and C–I⋯(I–Pt) interactions and their noncovalent nature. Full article

Nuclear factor-κB (NF-κB) signaling plays a pivotal role in regulating immune responses and is strongly implicated in cancer progression and inflammation-related diseases. The inhibitory κB kinases (IKKs), particularly IKKα, are central to modulating NF-κB activity, with distinct roles in the canonical and non-canonical signaling pathways. This study investigates the potential of selectively targeting IKKα to develop novel therapeutic strategies. A receptor–ligand interaction pharmacophore model was generated based on the co-crystallized structure of IKKα, incorporating six key features, two hydrogen bond acceptors, two hydrogen bond donors, one hydrophobic region, and one hydrophobic aromatic region. This model was used to virtually screen a diverse natural compound library of 5540 molecules, yielding 82 candidates that matched the essential pharmacophore features. Molecular docking and molecular dynamics simulations were subsequently employed to evaluate binding conformations, stability, and dynamic behavior of the top hits. The end-state free energy calculations (gmx_MMPBSA) further validated the interaction strength and stability of selected compounds. To experimentally confirm their inhibitory potential, key compounds were tested in LPS-stimulated RAW 264.7 cells, where they significantly reduced IκBα phosphorylation. These findings validate the integrative computational-experimental approach and identify promising natural compounds as selective IKKα inhibitors for further therapeutic development in cancer and inflammatory diseases. Full article

Background/Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the resistant pathogenic microorganisms that poses a global health threat due to its resistance to β-lactam antibiotics where the protein penicillin-binding protein 2a (PBP2a) plays a crucial role in its resistance. This study explores the potential of phytochemicals from Uvaria chamae, a plant with known medicinal properties, to serve as dual-site inhibitors of PBP2a, targeting both the active and allosteric sites. Methods: Phytochemicals previously identified in U. chamae were subjected to molecular docking and molecular dynamics simulations to evaluate their binding affinities and stability at PBP2a’s active and allosteric sites. The compounds’ pharmacokinetic profiles were predicted in silico using SwissADME tools. Root-mean-square deviation (RMSD), radius of gyration, and binding free energy were analyzed for dynamic stability. Results: Among the evaluated compounds, Uvarinol and Dichamanetin demonstrated high binding affinities compared to the co-crystallized ligand and standard antibiotics like ceftaroline. Uvarinol exhibited the highest binding affinity at both sites, with a docking score of −14.94 kcal/mol and a predicted inhibition constant (Ki) of 0.01 nM. Molecular dynamics simulations further confirmed the robust stability of Uvarinol and Dichamanetin, as indicated by consistently lower RMSD values relative to the co-crystallized ligand. Pharmacokinetic predictions revealed favorable drug-likeness and low toxicity, although Uvarinol showed limited gastrointestinal absorption. Conclusions: Uvarinol and Dichamanetin show promise as dual-site PBP2a inhibitors, offering a novel strategy to combat MRSA resistance. Their structural and pharmacokinetic properties make them viable candidates for further development, though experimental validation and formulation optimization are necessary to overcome bioavailability challenges. Full article

This review systematically examines the pivotal applications of the Density Functional Theory (DFT) in drug formulation design, emphasizing its capability to elucidate molecular interaction mechanisms through quantum mechanical calculations. By solving the Kohn–Sham equations with precision up to 0.1 kcal/mol, DFT enables accurate electronic structure reconstruction, providing theoretical guidance for optimizing drug–excipient composite systems. In solid dosage forms, DFT clarifies the electronic driving forces governing active pharmaceutical ingredient (API)–excipient co-crystallization, predicting reactive sites and guiding stability-oriented co-crystal design. For nanodelivery systems, DFT optimizes carrier surface charge distribution through van der Waals interactions and π-π stacking energy calculations, thereby enhancing targeting efficiency. Furthermore, DFT combined with solvation models (e.g., COSMO) quantitatively evaluates polar environmental effects on drug release kinetics, delivering critical thermodynamic parameters (e.g., ΔG) for controlled-release formulation development. Notably, DFT-driven co-crystal thermodynamic analysis and pH-responsive release mechanism modeling substantially reduce experimental validation cycles. While DFT faces challenges in dynamic simulations of complex solvent environments, its integration with molecular mechanics and multiscale frameworks has achieved computational breakthroughs. This work offers interdisciplinary methodology support for accelerating data-driven formulation design. Full article

Background/Objective: Cancer is the leading cause of death worldwide despite the diversity of antitumor therapies, which highlights the necessity to explore new anticancer agents. Methods: We synthesized 5,5-diphenylhydantoin derivatives including Schiff’s bases 7–27 and evaluated their cytotoxicity via the MTT assay. Enzymatic inhibition assays, cell cycle and apoptosis analyses, and molecular docking studies were also conducted. Results: Derivative 24 demonstrated the highest cytotoxic activity, with IC₅₀ values of 12.83 ± 0.9 μM, 9.07 ± 0.8 μM, and 4.92 ± 0.3 μM against the cell lines HCT-116, HePG-2, and MCF-7, respectively. Compounds 10, 13, and 21 showed potent antitumor activities versus the examined cell lines (average IC₅₀ = 13.2, 14.5, and 13.1 μM), respectively; moreover, these compounds also demonstrated promising EGFR and HER2 inhibitory activities, with IC₅₀ values in the range 0.28–1.61 µM. Derivative 24 displayed the highest EGFR and HER2 inhibitory activity values (IC₅₀ = 0.07 and 0.04 µM), respectively, which were close to those of the reference drugs erlotinib and lapatinib. Therefore, compound 24 was selected for further examinations and exhibited an inducing effect on apoptosis via diminishing the anti-apoptotic protein levels of BCL-2 (8.598 ± 0.29 ng/mL) and MCL-1 (261.20 ± 8.97 pg/mL) and promoting cell cycle arrest at the G2/M phase (33.46%). The binding relationships between compound 24 and the active sites of EGFR and HER2, which are similar to the co-crystallized inhibitors, were investigated using a molecular docking approach. Conclusions: These findings provide insights into the potential anticancer activities of the synthesized derivatives for further optimization to achieve therapeutic use. Full article

Solubility plays a crucial role in drug bioavailability and therapeutic efficacy. Febuxostat (FEB), a BCS Class II drug used to treat hyperuricemia and gout, has low solubility, limiting its effectiveness. Cocrystallization offers a strategy to enhance solubility without modifying the drug’s chemical structure. While FEB exhibits multiple polymorphic forms, no prior studies have explored cocrystal formation from its commercially available hemihydrate. This study examines whether FEB’s initial form—hemihydrate or anhydrous—affects cocrystal formation. We investigated cocrystals with aromatic amides (nicotinamide, isonicotinamide, and picolinamide) and explored new FEB cocrystals with aliphatic amides (diacetamide, malonamide, and D,L-lactamide) to assess solubility enhancement. Our results show that anhydrous FEB cocrystals reliably form with both aromatic and aliphatic amides, regardless of the starting material. However, the aliphatic coformers lead to thermally unstable cocrystals. Nevertheless, the new cocrystals significantly improved FEB’s solubility, with FEBH-LAC (13.9 mg/L) being the most soluble, but thermally unstable. FEBH-DIA showed the best balance, with 12.2 mg/L solubility and the fastest dissolution rate. These findings highlight cocrystallization with aliphatic amides as a promising approach for enhancing FEB’s solubility and therapeutic potential; however, they may pose problems with stability and reproducibility. Full article

The cocrystallization technique has been widely applied in the fields of energetic materials (EMs) to settle the inherent trade-off between high energy and low sensitivity in current high-energy molecules. Despite its widespread application, the mechanistic understanding of cocrystals growing from solutions remains largely underexplored. This paper presents a mechanistic model grounded in the spiral growth mechanism to predict the crystal morphologies of 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20) and 7H-trifurazano [3,4-b:3′,4′-f:3″,4″-d]azepine (TFAZ) cocrystals. In this model, it was assumed that CL-20 and TFAZ molecules incorporated into the crystal lattice simultaneously from solution as preformed growth units. The binding energies between the CL-20 molecule and TFAZ molecule were calculated to determine the most potential growth units. The predicted morphologies closely align with the experimental determinations supporting the model’s validity. Furthermore, the study found that the crystal habits were significantly influenced by the choice of solvents, due to variations in interfacial energetics affecting the growth process. Full article

The aim of our research was to understand the impact of ochratoxin A (OTA) exposure on various physiological and behavioral aspects in adult Wistar rats, and to evaluate the efficacy of a Syzygium aromaticum essential oil (EOC) treatment in restoring the damage caused by this toxin. The essential oils were extracted by hydrodistillation, a yield of 12.70% was obtained for EOC, and the GC-MS characterization of this essential oil revealed that its principal major components are eugenol (80.95%), eugenyl acetate (10.48%), β-caryophyllene (7.21%), and α-humulene (0.87%). Acute OTA intoxication was induced by an intraperitoneal (IP) injection of 289 µg/kg/b.w. every 48 h for 12 doses, resulting in significant reductions in the body and brain weights of exposed rats when compared with controls. The neurobehavioral analysis using several behavioral testing techniques, such as the forced swimming, the dark/light test, the Morris water maze, and the open field test, clearly revealed that OTA exposure causes neurobehavioral disorders, including decreased locomotor activity, a reduced willingness to explore the environment, reflecting a state of stress, anxiety and depression, as well as impaired memory and learning. In addition, OTA intoxication has been associated with metabolic disturbances such as hyperglycemia and hypercortisolemia. However, treatment with EOC mitigated these adverse effects by improving body and brain weights and restoring neurobehavioral function. The in silico analysis revealed significant affinities between clove oils and two tested esterase enzymes (ACh and BuChE) that were more than or similar to the four neurotransmitters “dopamine, serotonin, norepinephrine, and glutamic acid” and the co-crystallized ligands NAG, MES, and GZ5. These results highlight the therapeutic potential of EOC in combating the toxic effects of OTA and pave the way for future research into the mechanisms of action and therapeutic applications of natural compounds in the prevention and treatment of poison-induced diseases. Full article

We propose a hypothesis for the simultaneous emergence of bacteria, archaea, viruses, and mobile elements by sequential and concrete biochemical pathways. The emergence process can be considered analogous to crystallization, where genetic and biochemical systems stabilize as organisms evolve from their common ancestor, the LUCA, which was a non-free-living pool of single operon type genomes including double-stranded (ds) DNA at an ancient submarine alkaline vent. Each dsDNA operon was transcribed by different systems in σ, TFIIB, or TBP genomes. Double-stranded DNA operons can fuse and stabilize through the action of specific transcription systems, leading to differentiation between the Bacteria (σ genome) and Archaea (TBP genome) domains. Error catastrophe can be overcome by the parallel gain of DNA replication and DNA repair mechanisms in both genomes. Enlarged DNA enabled efficient local biochemical reactions. Both genomes independently recruited lipids to facilitate reactions by forming coacervates at the chamber of the vent. Bilayer lipid membrane formation, proto-cell formation with a permeable membrane, proto-cell division, and the evolution of membrane-associated biochemistry are presented in detail. Simultaneous crystallization of systems in non-free-living bacteria and non-free-living archaea triggered the co-crystallization of primitive viruses and mobile elements. An arms race between non-free-living cells and primitive viruses finally led to free-living cells with a cell wall and mature viruses. Full article

Apremilast (APR) is an anti-inflammatory drug commonly used in the treatment of psoriasis. In efforts to enhance its solubility, several cocrystals with similar structural features have been developed. This study investigates the cocrystallization of APR with four phenolic-type coformers: phenol, catechol, pyrogallol, and hydroxyquinol. These coformers differ in the number and position of their hydroxyl groups, with their melting points varying by as much as 100 °C. Four novel cocrystal forms were synthesized, purified, and characterized using X-Ray diffraction and thermal analysis techniques. Surprisingly, the resulting cocrystals exhibited minimal differences in their melting points. The molecular packing of APR appears to limit the network-forming potential of the hydroxyl groups, a conclusion supported by the solved crystal structures, Hirshfeld surface analysis, and differential scanning calorimetry (DSC) results. Full article