Letters in Organic Chemistry - Online First

A series of 4-(((8-hydroxyquinolin-7-yl)(phenyl)methyl)amino)-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one derivatives (4a–j) were synthesized via a one-pot, three-component reaction. The reaction employed benzaldehyde derivatives (1a–j), 4-aminoantipyrine (2), and 8-hydroxyquinoline (3), using titanium dioxide nanoparticles (TiO2 NPs) as a catalyst. The TiO2 NPs, synthesized through a sol–gel method, efficiently catalyzed the transformation under mild conditions, delivering high yields in just 9 minutes at room temperature. Optimization revealed that 0.010 g of catalyst in methanol was optimal, with protic solvents outperforming aprotic and non-polar ones. The reaction progress was monitored using thin-layer chromatography (TLC), and the final products were isolated via recrystallization. A systematic study of reaction parameters confirmed TiO2 NPs as an efficient, reusable, and environmentally friendly catalyst for multicomponent organic synthesis.

A growing number of applications in the fields of biotechnology, biomedicine, catalysis, and energy storage have resulted from the development of gold nanoparticles (AuNPs), which have garnered considerable attention in recent years due to their unique biochemical, optical, electronic, and catalytic properties. However, the traditional approaches to creating AuNPs, like chemical reduction and physical procedures, frequently call for the use of toxic solvents, dangerous compounds, and large energy inputs, raising questions about environmental sustainability and public health. In recent years, there has been a growing interest in the development of environmentally friendly and sustainable approaches to synthesize AuNPs, often referred to as “green synthesis” or “biogenic synthesis”. Green synthesis of AuNPs involves the use of biocompatible agents, such as plants, microorganisms, and biomolecules, to reduce gold ions and form AuNPs in a single step. Compared to conventional approaches, this strategy has a number of benefits, such as a reduced adverse effect on the environment, cheaper production costs, and better scalability. In this review, we will provide an overview of the current state of green synthesis of AuNPs, highlighting the various biogenic agents and characterization methods that have been employed to date. Furthermore, we shed light on the role of plant-derived biomolecules in the reduction mechanism and stabilization processes. Our review provides researchers with a standard reference for future studies.

The study aims to work on Computational Studies to Optimize Pyrazole Derivatives for Antibacterial Activity. A dataset of 28 Pyrazole derivatives having antibacterial activities was used to generate a pharmacophore hypothesis and a 3D-QSAR model. The established pharmacophore model (DHRRR_1) features three hydrogen bond donors (D), hydrophobic (H), and aromatic ring (R) features, exhibiting favorable parameters (R² = 0.9031; Q² = 0.9004). Hypothesis validation, enrichment analysis, and contour plot analysis were conducted, followed by virtual screening of the ChEMBL database using the optimized pharmacophore model and filtering based on the Lipinski rule of five. Docking was done with PDB ID 3G75 targeting DNA gyrase using Schrodinger software, further Desmond module of Schrodinger 2024-2 was used for MD simulations. The QSAR model was validated along with standard parameters. A library of NCE’s was designed with hypothesis DHRRR_1. Compounds that showed no violations in ADMET studies were further analysed for their interactions in the docking study. Eight compounds have shown zero violations in ADMET and have shown greater binding affinity in comparison to the standard Metronidazole. Further in the MD simulation results, instability of the complex 3G75-Comp D1 was analysed for 100 ns. This study provides a comprehensive approach for identifying novel Pyrazole-based antibacterial agents, highlighting compound D1 as a promising lead. Most promising compound D1 has indicated the role of the Hydroxy group, Pyrazole, and pyrrole ring for good antibacterial activity.

By employing a catalytic proportion of Co-Al2O3-SO3H in a three-component Biginelli-type condensation, combining various aromatic aldehydes, 1,3-cyclohexadione, and urea, practical one-pot synthesis of hexahydroquinazolinone was accomplished. This method yielded hexahydroquinazolinones in good yields, which were further enhanced under reflux conditions. This approach offers several significant advantages, including high efficiency, straightforward reaction conditions, simple workup, reusable catalysts, superior yields, and shorter reaction times. The structure of the produced heterogeneous catalyst Co-Al2O3-SO3H was analyzed using Brunauer-Emmett-Teller (BET) analysis, X-ray diffraction (XRD), and Scanning Electron Microscopy (SEM).

A new series of low molar mass mesogens having double lateral substituents were prepared and characterized with the objective to explore the effect of structure modification on the mesomorphic behavior. The molecular structure has three aromatic rings at the centre core system, which is connected by an imine linking group, two flexible alkyloxy chains at both sides of molecules and two lateral methyl groups attached to the core system. This low molar mass mesogen is known as bis(4-alkyloxybenzylidene)-2,5-dimethyl-1,4-phenylenediamine with different numbers of carbon (n) at the alkyloxy chain. Molecular structures were confirmed via infrared and nuclear magnetic resonance spectroscopic and mass spectrometric methods. Phase transition studies were conducted using a differential scanning calorimeter. Whereas, mesophase characterization was determined by polarizing optical microscopy and the temperature was varied with a temperature controller. The current core system of benzylidene-1,4-phenylenediamine showed good potential of exhibiting liquid crystal as all compounds were found to exhibit a nematic phase. Double lateral methyl atoms at the central mesogenic core had broadened the molecular width. This has caused a reduction in the overall lateral intermolecular attraction, and therefore, it exhibited a nematic phase. As the number of carbons at the alkyloxy chain increased, the clearing temperatures were observed to show a descending trend. A comparison of thermal properties was made between the current compounds with analogous compounds that do not possess any lateral substituent or have a single lateral substituent attached to the mesogenic core.

Steroidal saponins are natural compounds known to have anticancer activity by inducing apoptosis through inhibition of Bcl-2. This study was carried out on the potency, mechanism, and binding affinity of steroidal saponins present from Hoya verticillata var. verticillata as Bcl-2 inhibitor of colorectal cancer in silico using molecular docking and molecular dynamics simulation. All steroidal saponins exhibited hydrogen bonds in molecular docking, Van der Waals, and hydrophobic interactions. The binding potentials of steroidal saponins collected in previous studies and a reference compound, navitoclax, as target protein 6GL8 of BCL-2 inhibitor of colorectal cancer, were examined using molecular docking. The results showed the binding stabilities as -8.28, -8.87, -9.29, -11.09, -11.16, and -8.34 kcal/mol, respectively. Given the limited in-silico studies on pregnane saponins, we considered the extensive interest in these compounds. So, molecular dynamics studies were carried out to better comprehend the dynamics of ligands within the binding pocket of the target protein. Molecular dynamics simulation revealed that the binding of parasiticoside B to the 6GL8 receptor was stable and strong, based on their RMSD, RMSF, and the number of hydrogen bonds throughout the simulation. From the molecular interaction analysis derived from molecular dynamic trajectories of each ligand-bound complex, these interacting amino acids might be determined to play a crucial role in binding with the ligands of the 6GL8 active site. Parasiticoside B could be a good candidate for new inhibitors of anti-apoptotic BCL-2 proteins in colorectal cancer.

In this study, we aimed to describe a reconstructed hydrotalcite (Mg-Al LDH) catalyzed synthesis of β-hydroxy ketones from aldol condensation between acetone and aromatic aldehydes under room temperature. The performance of the catalyst, including catalytic activity, reaction selectivity, and reusability, as well as the general applicability of the catalytic method, was thoroughly evaluated. The reconstructed magnesium-aluminum hydrotalcite catalyst described in this study featured easy preparation, low cost, and high safety and efficiency, representing an excellent approach for catalyzing aldol condensation reactions under heterogeneous conditions.

The current work describes a unique iodine-mediated intra-molecular rearrangement of amide to nitrile and thiourea to urea, which took place simultaneously in thiophenes. The thiophenes having amide and amine groups at the adjacent positions were prepared via the Gewald reaction and subsequently treated with isothiocyanates in the presence of molecular iodine to get 1-(3-cyanothiophen-2-yl)-3-phenylureas in good yields. The synthesized compounds are of particular interest both chemically and biologically, as they contain thiophene, urea, and nitrile moieties in a single molecule. Many thiophene derivatives have been reported to exhibit antioxidant properties. Hence, the synthesized molecules were screened for their antioxidant activity by means of scavenger activity towards 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the Ferric Ion Reducing Power (FRAP) assay. Some compounds exhibited promising antioxidant properties.

Sheep pox virus (SPPV) presents considerable economic and health challenges, in particular for agricultural areas relying on sheep farming. SPPV encodes for SPPV14, a strong inhibitor of BCL-2-mediated apoptosis, which has sparked interest in identifying and developing multifaceted therapeutics. The SPPV14 protein is currently noticed as a crucial viral aspect that facilitates infection and advances the progression of the disease. Recent studies indicate that flavonoids, which are naturally occurring compounds known for their strong antiviral properties, could offer a promising strategy to inhibit SPPV infection. The current study attempted to explore the inhibitory ability of specific flavonoids on the SPPV14 protein utilizing an in silico molecular docking approach. A selection of ten flavonoids was made for virtual screening and docking studies aimed at the active site of the SPPV14 protein, emphasizing interactions at the Arg84 residue, which is essential for the stability of the viral protein. Using AutoDock Vina, molecular docking simulations were run to assess the binding affinities and possible inhibitory effects of flavonoids. All examined flavonoids exhibited significant binding affinities to SPPV14, with isoxanthohumol showing a remarkable interaction with the Arg84 residue, indicating increased stability in binding and possible inhibitory effects. The chosen flavonoids eliminated the canonical ionic interaction observed in all sheep pox disease SPPV14:BH3 motif complex resulting in apoptosis in SPPV14 docking investigation. These interactions suggest that flavonoids may have the ability to interfere with viral protein function, which may hinder the development of SPPV. In silico analysis suggests that specific flavonoids could act as effective antiviral agents against SPPV, with a particular focus on SPPV14. The findings establish a basis for following in vitro and in vivo investigations with the purpose of confirming the potential of flavonoids as alternative therapeutic agents for the management of sheep pox.

A novel and efficient method for synthesizing various quinoxaline derivatives has been developed, utilizing rainwater as both a solvent and a catalyst. This approach represents a significant advancement in green chemistry, as it combines simplicity, rapidity, and convenience while avoiding the need for toxic or expensive reagents. The synthesis involves the condensation reaction of aromatic 1,2-diamines with aromatic 1,2-dicarbonyl compounds. Traditionally, these reactions require specialized solvents and catalysts, but in this method, rainwater serves a dual function, streamlining the process and minimizing environmental impact. The use of rainwater not only simplifies the reaction setup but also provides an eco-friendly alternative to conventional organic solvents. The condensation leads to the formation of quinoxaline derivatives, a class of compounds known for their diverse biological and pharmacological activities. The reaction proceeds smoothly at ambient temperature, significantly reducing the energy requirements typically associated with chemical syntheses. This innovative synthesis method demonstrates the potential of using natural resources like rainwater in chemical reactions, contributing to sustainable practices in the field of organic synthesis. The versatility of the approach allows for the preparation of a variety of quinoxalines, offering promising applications in medicinal chemistry and material science. The rapid and straightforward process opens new avenues for the synthesis of quinoxalines, showcasing the potential of rainwater as a green solvent and catalyst in synthetic chemistry.