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An environmentally friendly, versatile multicomponent reaction for synthesizing isoxazol-5-one and pyrazol-3-one derivatives has been developed, utilizing a freshly prepared g-C3N4·OH nanocomposite as a highly efficient catalyst at room temperature in aqueous environment. This innovative approach yielded all the desired products with exceptionally high yields and concise reaction durations. The catalyst was well characterized by FT-IR, XRD, SEM, EDAX, and TGA/DTA studies. Notably, the catalyst demonstrated outstanding recyclability, maintaining its catalytic efficacy over six consecutive cycles without any loss. The sustainability of this methodology was assessed through various eco-friendly parameters, including E-factor and eco-score, confirming its viability as a green synthetic route in organic chemistry. Additionally, the gram-scale synthesis verifies its potential for industrial applications. The ten synthesized compounds were also analyzed via a PASS online tool to check their several pharmacological activities. The study is complemented by in silico molecular docking, pharmacokinetics, and molecular dynamics simulation studies. These studies discover 5D as a potential candidate for drug development, supported by its favorable drug-like properties, ADMET studies, docking interaction, and stable behavior in the protein binding cavity. [ABSTRACT FROM AUTHOR]

A highly efficient, facile and greener approach has been developed for the synthesis of bis(pyrazolyl)methanes. The method involves a reaction of 3‐methyl‐1‐phenyl‐2‐pyrazoline‐5‐one and substituted aromatic/heterocyclic aldehydes at ambient reaction conditions using ionic‐liquid, triethylammonium hydrogen sulfate to yield desired bis(pyrazolyl)methanes in excellent yields (85–96 %). The significant aspect of this protocol is the use of ionic liquid as a replacement of toxic and expensive metal catalysts thereby reducing the production of harmful chemical wastes and avoiding the use of toxic and volatile reagents in the synthesis. The catalyst was easily separated and reused up‐to five runs without significant decrease in its catalytic activity. Molecular docking studies were conducted on Cytochrome P450 3 A4, methylenetetrahydrofolate reductase, and tumor protein to predict their utility as potential anti‐oxidant, and anti‐cancer compounds. The outcome indicates that these synthesized compounds have the scaffold that binds well in the hydrophobic‐pocket of the respective enzyme and the polar groups present in their scaffold form hydrogen‐bonding too. Furthermore, we infer from the docking calculations that, all were docked in the binding domain of 4D75, eleven were docked in the active site of 6FCX and nine compounds were docked within the binding site of 3S7S. Furthermore, the in‐vitro antioxidant activity of synthesized compounds was explored against DPPH and ABTS, and most of the compounds were found to have high to excellent radical scavenging activity. [ABSTRACT FROM AUTHOR]

A heterogeneous, inexpensive and eco-friendly graphene oxide (GO) catalyst empowered the formation of bioactive biscoumarin derivatives involving domino Knoevenagel–Michael condensation using 4-hydroxycoumarin and aromatic aldehydes in H2O: EtOH solvent system. The prepared GO was well characterized by Fourier transform infrared (FT-IR), X-ray diffraction spectroscopy (XRD), field emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM) and thermogravimetric analysis (TGA). In this efficient, green, and sustainable one-pot synthesis, the target products were obtained in excellent yields (76–97%) in short reaction time (10–20 min.) and the catalyst can be easily recoverable and reusable for five consecutive cycles. Moreover, the use of economical and easily available substrate, low catalyst loading, shorter reaction time, gram scale applicability and high atom economy are the additional advantages of this greener approach. The inhibitory activity of the synthesized compounds was tested against two species of Gram-negative bacteria (E.Coli MTCC 46 and P. aeruginosa MTCC 2488), two species of Gram-positive bacteria (S. aureus MTCC 6980 and B. megaterium MTCC) and fungus (A. niger MTCC 1344) using the broth microdilution method. The electron withdrawing substituents like -CN, –F, and –Cl exhibited excellent activity against gram negative bacteria as compared to gram positive bacteria. Additionally, in silico studies were carried out on the selected DNA gyrase (1KZN) and human lanosterol 14 alpha-demethylase CYP51 (3LD6) to study the docking interactions of the synthesized compounds. It was observed that out of all the docked compounds, 4e (−23.966 kcal/mol) and 4i (−24.976 kcal/mol) showed highest docking score against 1KZN and 3LD6 protein, respectively. [ABSTRACT FROM AUTHOR]

A greener, scalable and mild mechanochemical protocol has been developed using readily available aromatic aldehydes and o-phenylenediamine in the presence of urea nitrate catalyst to afford 1,2-disubstituted benzimidazoles in few seconds. The highly efficient urea nitrate catalyzed synthesis proceeded via carbonyl activation-cyclization-atmospheric oxidation pathway. The method involved short reaction time (20–30 s), solvent free, easy preparation of catalyst, recyclable catalyst, easy isolation, high yield (92%–99%) at room temperature. Green chemistry matrix of synthesized compounds exhibited low e-factor (0.11), high atom-economy (90.74%), high reaction mass efficiency (89.9%) and excellent eco-score (78.5%). The molecular docking study of all the synthesized compounds for antibacterial and centromere associated protein inhibitor activity gave potential hits via presence of high interaction pattern. Compound 3b (−26.7009 kJ/mol) and 3k (−25.0285 kJ/mol) exhibited highest docking score with the selected 2XCS and 1T5C proteins, respectively. [ABSTRACT FROM AUTHOR]

The current study deals with the synthesis of some novel pyrimidine derivatives by the reaction of aromatic aldehydes, 2-aminobenzothiazole, and dimedone in the presence of thiamine hydrochloride (VB1) as an organocatalyst. The use of VB1 as a catalyst has eradicated the peril of metal contamination in the products that is viable for eco-friendly pathways and proven to be a better catalyst under sustainable conditions. The mechanism of the reaction involved Knoevenagel condensation followed by Michael addition. The designed protocol has many fascinating features, viz. high product yields, eco-friendly, milder reaction conditions, avoiding the use of hazardous solvent, and easily recoverable and reusable catalyst. The good functional group tolerance with a series of derivatives has been demonstrated. Molecular docking studies were performed on the synthesized compounds using Staphylococcus aureus dihydropteroate synthase (saDHPS) (6CLV) and DNA gyrase (1KZN) proteins. Furthermore, the binding mode of the ligands with the protein study was quite promising. Among the synthesized compounds, compound 5e was found to be the most potent and showed good binding interactions and the highest docking score against both proteins, 1KZN and 6CLV. [ABSTRACT FROM AUTHOR]

A green and eco‐benign synthesis of biscoumarin derivatives using carbon sulfonic acid, a solid support catalyst has been described. The reaction involved a one‐pot two‐component reaction of 4‐hydroxycoumarin and aldehyde using carbon sulfonic acid involving Knoevenegal‐Michael condensation. A series of aromatic (bearing electron withdrawing and releasing group) and heteroaromatic aldehydes has been converted to biscoumarins with excellent isolated yields. The reaction is in compliance with green principles, that is, inexpensive catalyst, easy to prepare, nontoxic, easy handling, reusable up to five recycle runs, easy separation, short reaction time, no need of time consuming column purification, high yielding, and so on. The synthesized catalyst and biscoumarin derivatives were well characterized by spectral analysis. The molecular modeling studies showed that the designed molecular scaffolds (3a‐j) showed outstanding interaction with methylenetetrahydrofolate reductase (MTHFR) and cytochrome P450 3A4 (CYP3A4) proteins. It was noticed that 3f (−17.55 kJ/mol) and 3d (−26.23 kJ/mol) showed the highest docking score against CYP3A4 and MTHFR proteins, respectively. [ABSTRACT FROM AUTHOR]

In this article, we have established a highly promising approach for the synthesis of biscoumarins via domino Knoevenagel–Michael condensation of 4-hydroxycoumarin and aromatic aldehydes in 2:1 ratio using carbon-SO3H as a solid acid catalyst in H2O: EtOH (1:1). This new protocol produced α,ά-benzylidene bis(4-hydroxycoumarin) derivatives in high to excellent yields. For this, carbon-SO3H solid acid catalyst has been prepared from glycerol and sulfuric acid and characterized by FT-IR, SEM, TGA, and X-ray diffraction methods. This approach has several advantages such as high atom-economy (96.05%), excellent yields (88-100%), no need of further purification techniques, that is, column chromatography, easy workup, less reaction time, cost-effective, avoid the use of hazardous solvents, recyclability of catalyst, etc. Moreover, molecular docking studies have been performed on selected proteins methylenetetrahydrohyrofolate reductase (MTHFR) and cytochrome P450 3A4 (CYP3A4) to identify the potency of the synthesized compounds (3a–j). Among the synthesized compounds 3i, 3e, and 3b showed the highest docking score against both the proteins. [ABSTRACT FROM AUTHOR]

• A highly efficient pathway of acridinediones synthesis was reported. • The use of green and biodegradable catalyst, Chitosan-SO 3 H and broad substrate scope make them economical, sustainable and eco-benign protocol. • Molecular docking, MD simulation and DFT studies were performed. • Significant in-silico activity was shown against Human Topoisomerase II beta and Staphylococcus aureus tyrosyl-tRNA synthetase. An efficient and ecobenign pseudo one-pot multicomponent synthesis of acridine-1,8-diones has been investigated using biodegradable and heterogeneous catalyst, chitosan-SO 3 H under ambient reaction conditions. The highly proficient reaction of dimedone, aldehydes, and ammonium acetate in aqueous ethanol using chitosan-SO 3 H catalyst at room temperature showed high yields in short reaction time. The bioactivity of molecules was further studied through molecular docking and molecular dynamics simulations, protein-ligand interaction energy calculations and DFT studies. Among all, compounds 4e, 4f (– 11.8 kcal/mol) , 4g, 4x and 4c (– 10.8 kcal/mol) , 4d, 4i, 4s were the most potent against Human Topoisomerase II beta (3QX3) and Staphylococcus aureus (S. aureus) tyrosyl-tRNA synthetase (1JIJ), respectively and displayed good binding affinity and interaction pattern. Easy availability of substrate and catalyst, use of biodegradable and recyclable polymeric solid acid catalyst, avoid the use of toxic and metallic reagents, operational simplicity, no need of column chromatography, easy workup, clean reaction profile, high yields (70–95%) and purity in short time period (3–12 min) with wide substrate scope (32 derivatives including 10 novel) and broad spectrum of bioactivity are notable advantages of the present protocol. [Display omitted] [ABSTRACT FROM AUTHOR]