Aryl Aldehydes Research Articles

Cu (ii) Immobilized on Mesoporous Poly (Guanidine–Triazine–Sulfonamide) (PGTSA/Cu): A New Catalyst for the Synthesis of Tetrazolo[1,5‐a]pyrimidines

ABSTRACTThe study focuses on the synthesis and characterization of a new mesoporous polysulfonamide stabilizer using condensation polymerization and the nanocasting technique. The resulting material, PGTSA, was modified with copper ions and used as a nanocatalyst in the reaction of benzaldehydes, 1H‐tetrazole‐5‐amine, and malononitrile. The performance of the mesoporous PGTSA/Cu (II) was compared with non‐porous PGTSA/Cu (II), highlighting the significance of support porosity in catalytic activity and loading of copper species. Based on the analysis of the ICP and catalytic performance, it was observed that mesoporous PGTSA/Cu (II) exhibited a higher level of catalytic activity compared to PGTSA/Fe3O4/Cu (II) and non‐porous PGTSA/Cu (II). Also, the catalytic activity of the aryl aldehyde was significantly influenced by its electrical characteristics. The recovery and reusability of the PGTSA/Cu (II) catalyst are noteworthy aspects, highlighting the practicality and sustainability of the catalytic system. The amount of copper in fresh catalyst and the recycled catalyst after six times recycling is 1.57% and 1.52%, respectively. Therefore, ICP‐OEIS analysis indicated that copper leaching of this catalyst is very low. The procedure offered high product yields, easy recovery of the nanocatalyst, remarkable reusability, short reaction times, and compatibility with various substrates.

Photoreductive N-N Homocoupling Catalyzed by a Superphotoreductant.

Azines are valuable synthons or target molecules in organic synthesis. In this work, we report that CBZ6 could work as a photoreductive catalyst for the N-N homocoupling of oximes in high efficiency. This therefore enabled convenient access to a large variety of azines from the corresponding aryl and alkyl ketones, as well as aryl aldehydes in up to 99% yield. 2,4-Dinitrophenoxyl was used as the recyclable auxiliary and the CBZ6 photocatalyst could also be recycled. These together with the low catalyst loading (2 mol % of CBZ6), the short reaction time (4 h), and the nontoxic DMSO solvent make the current process a sustainable and practical alternative to the classic methods.

Highly selective electrosynthesis of imines via electroreduction coupling of nitroarenes with aryl aldehydes on Co9S8 with positively charged sulfur vacancies

The electrocatalytic synthesis of imines through the reductive imination of nitroarenes with aldehydes is a facile, environmentally friendly, and valuable process. In this study, high selectivity electrosynthesis of imines was realized through the electrocatalytic C-N coupling reaction between nitroarenes and aryl aldehydes on Co9S8 nanoflowers with rich sulfur vacancies (Co9S8-Vs). Comparative experiments revealed that positively charged sulfur vacancies play a pivotal role in boosting catalytic selectivity towards imines. Electron-deficient sulfur vacancies intensified the adsorption of negatively charged Ph-NO2, thereby enhancing the conversion rate of the electrochemical nitrobenzene-reduction reaction (eNB-RR). Simultaneously, sulfur vacancies augmented the adsorption capability of negatively charged Ph-CHO, enriching Ph-CHO species at the electrode interface and expediting the Schiff base condensation reaction rate. The experimental results show that the reaction conditions can satisfy the different nitroarenes and aryl aldehydes in the electrocatalytic aqueous-phase system under mild conditions to obtain the corresponding imine products in high selectivity. This study provides a facile and environmentally friendly pathway for future electrocatalytic synthesis of imine.

Synthesis, C-N/N-N bond conformational analysis and evaluation of naphtho[2,3-d][1,2,3]triazole-4,9-dione tethered N-acyl hydrazones as α-amylase inhibitors: Insights from molecular modeling and ADMET analysis

In an effort to expand the repertoire of potent α-amylase inhibitors, we sought to develop novel inhibitors by combining 1,4-naphthoquinone, 1,2,3-triazole, and N-acyl hydrazone scaffolds in a single matrix. To achieve this, twelve novel naphtho[2,3-d][1,2,3]triazole-4,9‑dione tethered N-acyl hydrazones were synthesized through condensation reaction of 2-(4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]triazol-1-yl)acetohydrazide with various substituted aryl aldehydes. Structural elucidation for all the compounds was performed using 1D, 2D-NMR, FTIR, and mass spectral analyses. The synthesized molecules were evaluated for their ability to inhibit α-amylase activity using acarbose as the standard drug. All the derivatives exhibited potent inhibition of α-amylase, with IC50 values ranging between 17.26 ± 0.07 to 25.62 ± 0.03 μg/mL. Notably, compound 9c possessing –meta substituted –NO2 group displayed the highest activity (IC50 = 17.26 ± 0.07 μg/mL) among the series. Structure-activity relationship (SAR) revealed the pivotal role of aryl ring substitutions in determining inhibitory efficacy. To validate these findings and to assess the binding stability of 9c within the catalytic site α-amylase dervied for A. oryzae (PDB ID:7TAA), in silico studies were performed. The compound 9c effectively occupies the enzyme's active pocket, with minimal RMSD fluctuations observed over 100 ns simulation, indicating stable protein-ligand complex. ADMET predictions suggested favorable drug-like properties, underscoring the potential of these compounds as novel α-amylase inhibitors for managing type 2 diabetes mellitus

Sustainable and Advanced LED-Implanted Microfluidic Photoreactor with Coupled Optical Fiber Enabling Efficient Photocatalytic Synthesis Beside Online Reaction Progress Monitoring.

The conventional methods for the photoinduced synthesis of benzimidazoles may need further improvement regarding a safer and energy-efficient synthesis platform with in-process monitoring for maximum yield within a much reduced reaction time. This work describes the use of a novel optofluidic Lab-on-a-Chip technology for safer, energy-efficient, and expedited synthesis of benzimidazole derivatives in excellent yields along with real-time quantitative measurement during product formation. This innovative method involves synthesis within LED-embedded microfluidic reactors, allowing for rapid synthesis of benzimidazole derivatives via photoinduced condensation cyclization reactions of aryl aldehydes and o-phenylenediamines using a Rose Bengal/fluorescein photocatalyst. It results in good to excellent yields (85-94%) in a notably shorter period of time (10 min) as compared to that for the batch protocol reaction (2-3 h). The incorporation of a reaction-monitoring microfluidic device precisely connected to the microfluidic reactor (microreactor) unit successfully avoids interference from light sources, ensuring consistent UV-vis spectroscopic observations of the produced benzimidazole derivatives. This LED-embedded microfluidic device's capability of photoinduced synthesis, along with real-time spectroscopic analysis, represents a promising breakthrough in organic synthesis. The proposed approach minimizes the potential for accidents, prevents waste of chemicals, maximizes atom economy, and designs an energy-efficient synthesis route, along with real-time in-process monitoring.

Design, Synthesis, and Study of Novel Memantine Schiff Base Derivatives Against Targeted Enzymes in Alzheimer’s Disease

Introduction: According to WHO, Alzheimer’s disease was estimated at 74.4 million cases in 2023, which will increase by 152.8 million cases in 2050. The therapeutic options available in the market for the treatment of AD are only capable of reducing the symptoms of dementia but not preventing progressive degeneration. Memantine is a non-competitive NMDAR antagonist used for the treatment of patients with moderate-to-severe AD, but it has a high toxicity profile. To counter this, the Memantine Schiff base derivatives were designed as simple and lowtoxicity compounds. Materials and Methods: Molecular docking was performed against the targeted enzymes Acetylcholinesterase and Butyrylcholinesterase using AUTODOCK 1.5.7 software. A series of novel Memantine derivatives of Schiff base were synthesized by condensing Memantine with various aryl aldehydes and screened for their invitro-cholinesterase inhibitory activity towards Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE) by Ellman’s method. Results and Discussion: Among the designed compounds, compounds LMV and LMC showed maximum binding scores of -10.35 kcal/mol and -10.12 kcal/mol, respectively, than the standard Donepezil (-8.78 kcal/mol) against Acetylcholinesterase. The compounds LMONB and LMDMB produced significant binding scores of -9.31 kcal/mol and -9.11 kcal/mol, respectively, compared to the standard Donepezil (-7.57 kcal/mol) against Butyrylcholinesterase. Also, compounds LMV (30.9 ± 2.13 μM) and LMDMB (13.51 ± 1.12 μM) showed potent inhibitory activity against the AChE and BChE. These compounds possess drug-like characteristics and are also capable of crossing the Blood Brain Barrier (BBB). Conclusion: The studied compounds LMV and LMDMB, being non-toxic, obey Lipinski’s rule of 5 and are potential inhibitors against targeted enzymes, which may be promising clinical candidates for treating Alzheimer’s disease.

Screening of synthesized perimidine compounds for the assessment of antimicrobial potential: in-vitro and in-silico molecular docking and molecular dynamics simulation studies

Presently, antimicrobial resistance is a major and worldwide concern due to high rate of mutation in microorganisms, widespread use, lack of efficacy of drugs, and low drug discovery rate. Considering the importance of N-heterocycles as antibiotics, perimidine derivatives 3(a–v) have been synthesized via cyclocondensation reaction of 1,8-diaminonaphthalene and aryl aldehydes. Further, the synthesized perimidines 3(a–v) were screened as potent antimicrobial agents via in-vitro, in-silico, ADME and MD simulation studies. All 22 derivatives 3(a–v) were studied against two-gram +ve (E. coli and P. aeruginosa), two-gram −ve (S. aureus and B. subtilis), and two fungal (A. niger and S. cerevisiae) strains using ciprofloxacin and fluconazole as reference drugs. The in-vitro study results showed that compounds 3e, 3h, 3l, and 3m were the most potent against S. aureus and 3(a–d), 3(g–i), and 3s were the most active against B. subtilis as compared to the standard. Furthermore, molecular docking studies were performed against Dihydrofolate reductase (PDB Id: 3SRW) from S. aureus, DNA gyrase (PDB Id: 4DUH) from E. coli, and ERG11 gene (PDB Id: 4LXJ). Compounds 3f, 3f/3m, and 3o were found to bind efficiently with the highest binding energy − 10.6, − 9.6, and − 11.3kcal/mol depicting the potential inhibitor of 3SRW, 4DUH, and 4LXJ receptor protein, respectively. The drug-likeness properties of compounds were studied using SwissADME program. To further validate these findings, molecular dynamics simulations were conducted to evaluate their binding stability. From simulation studies, it was observed that all the shortlisted compounds displayed stable binding within the active site of the selected proteins.Graphical abstract

Green Chemical Synthesis of Cube‐Shaped CuFe2O4 Nanoparticles for Use as Magnetically Retrievable Catalysts in A3 Coupling Reactions

ABSTRACTA3 coupling reaction is a multicomponent reaction (MCR) involving aryl aldehydes, phenyl acetylenes and amines to synthesize a variety of biologically active propargylamine derivatives. Herein, we report the preparation of cube‐shaped CuFe2O4 nanoparticles (NPs) via the hydrothermal method in the presence of Lantana camara flower (LCF) extract to use them as catalysts to synthesize propargylamine derivatives. X‐ray diffraction study confirms the formation of CuFe2O4 NPs with cubic spinel structures. In the presence of LCF extract, cube‐shaped CuFe2O4 NPs are formed predominantly irrespective of the type of alkali used as the hydrolyzing agent. However, a mixture of nearly spherical and cube‐shaped particles has been formed in the absence of additives. The synthesized CuFe2O4 NPs exhibit superparamagnetic behaviour and are magnetically ordered. The synthesized cube‐shaped CuFe2O4 NPs exhibit excellent catalytic activity in the A3 coupling reaction between benzaldehyde, piperidine and phenylacetylene to give propargylamine with a yield of 90% under the optimum conditions. The catalyst is highly stable and magnetically retrievable facilitating reusability for up to five cycles without considerable loss of catalytic activity. The protocol is suitable for the synthesis of a diverse range of propargylamine derivatives with moderate to excellent yield.

Flux-Screened Copper/Electric Dual-Catalyzed Chemo- and Enantioselective Ullmann-Type C-C Coupling Reactions.

This study introduces an innovative copper/electric dual-catalyzed approach to Ullmann coupling reactions. Our research delineates a series of chemoselective cross-couplings among various halogenated aromatics and enantioselective couplings involving halogenated aryl aldehydes. We employed a flux screening technique to refine the reaction parameters, which is rarely reported in the field of electrochemical synthesis. This advancement accelerates the determination of optimal reaction conditions and affords some inspiration for developing sustainable and ecofriendly chemical synthesis.

Unsymmetrical ferrocene-based azines: Facile synthesis, investigation of spectral and electrochemical properties, and antibacterial activity

Ferrocenyl azines have been utilized in metal ion detection, as a ligand in the synthesis of metal complexes, in catalysis, in dye-sensitized solar cells, and in studies on antiparasitic, antitumor, and antileishmanial. However, most of the challenging synthesis routes require temperature control, expensive starting materials, and additional steps. In this research, a series of new unsymmetrical ferrocene-based azines (2a-j and 4a-j) were simply synthesized from the reaction of ferrocenecarboxaldehydehydrazone (1) and 1,1′-ferrocenedicarboxaldehydehydrazone (3) with various aryl aldehydes in moderate to good yield (40–80 %). All compounds were characterized using FT-IR, 1H and 13C NMR, and LC-MS. In addition, the molecular structure of 2b and 2h were determined by X-ray structure analysis. UV–Vis spectra of azines revealed weak absorbance in the 460–490 nm region for the d → d transition of Fe(II) and two strong absorbances in the range of 250–350 nm for π → π* and n → π* of aromatic rings and azine bridges. Cyclic voltammetry demonstrated higher half-wave potentials (E1/2) for all ferrocenyl azines in comparison to ferrocene as the internal standard, with a significant decrease of E1/2 for ferrocenyl-rich derivatives. The antibacterial activities of all synthesized ferrocenyl azines were also investigated against Staphylococcus aureus (gram-positive) and Escherichia coli (gram-negative) bacteria. Two ferrocene-rich compounds, 2i and 4j, have shown significant activity against Staphylococcus aureus.

Iodine‐Promoted Cascade Redox Cyclization to Access 2‐Arylbenzothiazoles Using Elemental Sulfur

ABSTRACTA straightforward and efficient method has been developed to access a variety of benzothiazole derivatives via cascade reductive annulation. Iodine mediated, one‐pot three‐component reaction of o‐chloronitroarenes, aryl aldehydes, and elemental sulfur effectively produce benzothiazoles. Moreover, the metal‐free strategy allows the facile synthesis of diverse 2‐substituted benzothiazoles through multiple carbon–heteroatom bonds in good yields. The present protocol features a greener approach, readily accessible reagents, broad substrate scope, high product yields, and operational simplicity.

One-pot Three-component Synthesis of Fully and Diversely Functionalized Pyrans and Spiropyrans Using Sodium Formate as Catalyst in Aqueous Ethanol at Room Temperature

Abstract: A convenient and general method has been developed for the synthesis of fully and diversely functionalized pyrans via one-pot three-component reactions of various aryl or heteroaryl aldehydes, malononitrile, and 1,3-dimethyl/1,3-diethyl-acetonedicarboxylates in the presence of a catalytic amount of sodium formate as an efficient organocatalyst in aqueous ethanol at room temperature. All the scaffolds were synthesized in excellent yields within 2.5 hours. Under the same reaction conditions, fully and diversely functionalized spiro-pyrans were also synthesized in excellent yields from the reaction of isatin, malononitrile, and 1,3-dimethyl/1,3-diethylacetonedicarboxylates. All the products were isolated pure just by simple filtration. Synthesis of fully and diversely functionalized biologically promising pyrans, excellent yields, use of organocatalyst, less toxic solvent, no column chromatographic purification, and energy efficiency are some of the major advantages of this newly developed protocol. method: In a clean test tube a magnetic stir bar, 0.5 mmol of aldehydes (1a-1i), 0.5 mmol of malononitrile (2; 0.033 g) and 0.5 mmol of 1,3-dimethylacetonedicarboxylate (3a; 0.087 g) or 1,3-diethylacetonedicarboxylate (3b; 0.101 g), 4 ml aqueous ethanol (1:1 v/v) and 20 mol% sodium formate were taken sequentially. The whole reaction mixture was stirred at room temperature for the time mentioned in Table 2. The progress of reaction was monitored by TLC. By using the same amount of catalyst and solvent the synthesis of methyl/ethyl-2'-amino-3'-cyano-6'-(2-meth/ethoxy-2-oxoethyl)-2-oxospiro[indoline-3,4'-pyran]-5'-carboxylate (6a/6b) was achieved from the reactions of 0.5 mmol of isatin (5; 0.0735 g), 0.5 mmol of malononitrile (2; 0.033 g) and 0.5 mmol of 1,3-dimethylacetonedicarboxylate (3a; 0.0871 g) or 1,3-diethylacetonedicarboxylate (3b; 0.1011 g). After the completion of each reaction, the desired products were isolated simply by filtration and subsiquent washing with aqueous ethanol (EtOH:H2O = 1:1).

Microwave and ultrasound-assisted green protocols for 5-methylthiazole induced Betti bases: molecular docking, in-silico pharmacokinetics, and anticancer activity studies

ABSTRACT Herein, we describe an efficient one-pot three-component microwave and ultrasound-endorsed approaches for synthesizing distinct 5-methylthiazole induced Betti bases (5-methyl-thiazol-2-ylamino-aryl-benzylnapthols) employing silica sulfuric acid (SSA, silica-OSO3H) as an active heterogeneous acid catalyst. The title compounds produced in good yields (86–95%) from naphthalen-2-ol, 5-methylthiazol-2-amine, and assorted aryl aldehydes; and structurally characterized by spectral and elemental analyses. A comprehensive comparative study of conventional, ultrasonic, and microwave-irradiated synthetic routes has been achieved by optimizing various reaction parameters. These new protocols provide several advantages, including the use of an inexpensive, non-toxic, and reusable catalyst. Additionally, they benefit from mild reaction conditions, short reaction times, and simple workup and purification procedures, thereby increasing their practicality. Furthermore, the synthesized compounds were evaluated for their anticancer potency against A-549 (lung cancer) and A-498 (kidney cancer) cell lines, with scaffold IVa demonstrating excellent (GI50 < 10 µg/mL) inhibitory activity against A-549. Additionally, molecular docking was performed to investigate potential binding interactions between ligands and proteins. Scaffold IVa exhibited the best docking with cancerous target proteins 1M17 (−8.9 kcal/mol) and 1M14 (−7.2 kcal/mol), thereby supporting our bio-activity studies.

Microwave-Assisted Hydrolysis of Ethyl Azolylacetates and Cinnamates with K2CO3: Synthesis of Potassium Carboxylates.

In this study, the hydrolysis of ethyl azolylacetates and ethyl cinnamates using K2CO3/ethanol under microwave irradiation was developed. For this purpose, ethyl azolylacetates were first synthesized by nucleophilic substitution between the corresponding azole and ethyl bromoacetate under sonication at 50 °C for 3 h, yielding derivatives with 10-92% chemical yields, while ethyl cinnamates were obtained by a microwave-assisted Horner-Wadsworth-Emmons (HWE) reaction of triethyl phosphonoacetate with a variety of aryl aldehydes at 140 °C for 20 min, yielding derivatives with moderate to high yields (67-98%). Initially, the optimization of the hydrolysis reaction was performed using ethyl pyrazolylacetate as a model starting material while varying the temperature, time, and base equivalents; the best results were achieved by carrying out the reaction at 180 °C for 20 min with 3.0 eq of K2CO3. This simple and greener method facilitated the synthesis of potassium carboxylates in moderate to high yields, 80-98% for azolyl derivatives and 73-98% for cinnamate derivatives. The structures of all potassium carboxylates were confirmed by FTIR, 1H, 13C NMR, and HRMS.

2‐Ethenyl Imidazolium Salts: Synthesis, Characterization, and Evaluation as Potential Chemotherapeutics

AbstractAs candidates for intravesical exfoliants to treat bladder cancer, we have prepared fourteen new imidazolium compounds substituted at the 2 position. These compounds were produced by use of the Knoevenagel reaction between a series of aryl aldehydes and 2‐methyl imidazolium salts. Two azolium systems were examined (benzimidazole and 4,5‐dichloroimidazole) and each of these heterocycles are substituted off the nitrogen atom positions with naphthalen‐2‐ylmethyl groups. NMR spectroscopy confirms formation of the carbon‐carbon double bond, and X‐ray crystallography confirmed that the alkenes adopt the E conformation. These new imidazolium salts were evaluated for their chemotherapeutic activity using the NCI‐60 Human Tumor Cell Line Screen, and we observed that the benzimidazolium systems were more toxic than the dichloroimidazolium systems, and that the methyl phenol ether or dimethyl aniline modified compounds showed the highest activities.

Resolving the metabolism of monolignols and other lignin-related aromatic compounds in Xanthomonas citri

Lignin, a major plant cell wall component, has an important role in plant-defense mechanisms against pathogens and is a promising renewable carbon source to produce bio-based chemicals. However, our understanding of microbial metabolism is incomplete regarding certain lignin-related compounds like p-coumaryl and sinapyl alcohols. Here, we reveal peripheral pathways for the catabolism of the three main lignin precursors (p-coumaryl, coniferyl, and sinapyl alcohols) in the plant pathogen Xanthomonas citri. Our study demonstrates all the necessary enzymatic steps for funneling these monolignols into the tricarboxylic acid cycle, concurrently uncovering aryl aldehyde reductases that likely protect the pathogen from aldehydes toxicity. It also shows that lignin-related aromatic compounds activate transcriptional responses related to chemotaxis and flagellar-dependent motility, which might play an important role during plant infection. Together our findings provide foundational knowledge to support biotechnological advances for both plant diseases treatments and conversion of lignin-derived compounds into bio-based chemicals.

Photocatalyzed Synthesis of a Schiff Base via C-N Bond Formation: Benzyl Alcohol as Sustainable Surrogates of Aryl Aldehydes.

The advancement of photocatalytic techniques has enabled green chemical synthesis through visible-light-mediated photochemical oxidation under mild conditions. A novel approach under visible-light conditions was facilitated by eosin-Y for the reaction between substituted benzyl alcohols and anilines, resulting in the synthesis of diverse Schiff bases. This innovative method is emphasized for its environmentally friendly nature, lack of metal catalysts, cost-effectiveness, and nontoxic characteristics.

Biosynthesis of Ag‐CuO Nanocomposites: Efficient Catalyst for the Synthesis of Schiff Bases, Photodegradation of Congo Red Dye and Their Cytotoxicity Evaluation on MCF‐7 Cell Line

ABSTRACTAmid growing environmental concerns and the need for a sustainable future, green synthetic methodologies are gaining popularity for their simplicity and nontoxicity. In pursuit of the eco‐friendly synthesis of nanomaterials, the study reports an innovative synthesis of Ag‐CuO nanocomposites via the coprecipitation method utilizing Citrus limetta fruit juice extract as the bioreductant and stabilizing agent. The morphological and structural characteristics of the fabricated nanocomposites were evaluated by ultraviolet–visible diffuse reflectance spectroscopy (UV–vis DRS), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy‐dispersive X‐ray (EDX), transmission electron microscopy (TEM), X‐ray diffraction (XRD), Raman and Brunauer–Emmett–Teller (BET) analyses. The nanocomposites were crystalline with particle sizes ranging from 15 to 24 nm and exhibited spherical and rod‐like shapes. The band gap value and specific surface area of the nanocomposites were found to be 1.5 eV and 25.50 m2/g, respectively. The photoluminescence (PL) analysis and electrochemical studies revealed significant charge separation and effective charge migration behaviour of the nanocomposites, respectively. The nanocomposites effectively catalysed the synthesis of Schiff bases from aryl aldehydes and aromatic amines at room temperature and without solvents. The reactions proceeded in a brief time with excellent product yields, and the nanocatalyst retained its activity for five consecutive cycles. The nanocomposites also efficiently catalysed the photodegradation of Congo red dye under visible light. A significant degradation of 94.33% was attained in 55 min, and the nanocatalyst maintained its efficacy over four consecutive reaction cycles. Moreover, the nanocomposites exhibited notable anticancer properties against the MCF‐7 (human breast) cell line, demonstrating a remarkable cytotoxicity rate of 87.79%. The findings highlight the efficacy of the biosynthesized nanocomposites in catalysis, environmental remediation and biological applications.

Ni-Fe2O3@SiO2-Pr-DBU: A novel efficient magnetically retrievable catalyst for one-pot synthesis of dihydropyrano [3,2-c] chromene

In the present work, Ni-Fe2O3@SiO2-Pr-DBU was synthesized as a novel magnetically separable nano-catalyst and characterized by various techniques like Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), Scanning electron microscopy (SEM), Vibrating-sample magnetometry (VSM), Transmission electron microscopy (TEM) and Elemental analysis by energy dispersive X-ray (EDX). The catalytic efficiency of NiFe2O3@SiO2-Pr-DBU was explored in the synthesis of dihydropyrano[3,2-c] chromenes through a one-pot multicomponent reaction of 4-hydroxycoumarin, malononitrile, and aryl aldehydes in aqueous solution at ambient temperature condition. An external magnet easily removed the nano-sized magnetic core catalyst from the synthesized reaction mixture. It was recycled for five successive runs while maintaining its potential and adhering to our green synthesis approach. We used dihydropyrano chromene, a highly biologically active commercial compound, to prepare some novel derivatives.

2-amino-6-ethoxy-4-arylpyridine-3,5-dicarbonitrile Scaffolds as potential acetylcholinesterase and butyrylcholinesterase inhibitors

Inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes are of prime importance for treating Alzheimerʼs disease (AD). Apart from many organic scaffolds, pyridine-based compounds have previously been reported as potential α-glucosidase inhibitors. The current study reports a series of pyridine-based synthetic molecules for their acetylcholinesterase AChE and butyrylcholinesterase BChE inhibitory potential assessed via in vitro, kinetics, and in silico studies. For this purpose, 2-amino-6-ethoxy-4-arylpyridine-3,5-dicarbonitrile analogs 1–23 were synthesized by using a two-step reaction scheme. In the first step, different aryl aldehydes were treated with malononitrile to afford the 2-benzylidenemalononitrile in the presence of catalyst ammonium acetate. In the next step, 2-benzylidenemalononitrile intermediates were reacted again with malononitrile, catalyzed by potassium hydroxide, to synthesize a range of functionalized pyridine scaffolds in good yields. Compounds were subjected to in vitro screening against AChE and BChE enzymes. Several derivatives, including 2, 3, 11, 14–16, 19, 20, and 22, showed many folds of increased inhibitory potential and binding affinity in the ranges of Ki = 1.62 ± 0.13 nM to 15.84 ± 0.10 nM for AChE and Ki = 1.35 ± 0.31 nM to 13.52 ± 0.61 nM for BChE, as compared to the standard tacrine Ki = 53.31 ± 11.32 nM for AChE, and Ki = 58.16 ± 7.24 nM for BChE. Further, molecular docking studies deduced key interactions between the ligands (compounds) and the active pocket of enzymes. The current research study has identified several potential AChE and BChE inhibitors that may serve as lead candidates after targeted advanced research for exploring anti-Alzheimer agents.