A series of one-pot, atom-economic, in parallel three and five-component reactions for the synthesis of acridine and bis(2-benzyl-5,5-dimethylcyclohexane-1,3-dione)-N-and 4-disubstituted naphthylamine derivatives under green conditions from the reaction between dimedone, aryl aldehydes, and 1naphthylamine have been investigated. The three-component route to the synthesis of acridine derivatives is well-known, but the five component route results in bis(2-benzyl-5,5-dimethylcyclohexane-1,3 dione)-N-and 4-disubstituted naphthylamine derivatives, which is an unprecedented pathway and is reported herein for the first time. By this achievement, a broad range of novel acridine and bis(2-benzyl 5,5-dimethylcyclohexane-1,3-dione)-N-and 4-disubstituted naphthylamine derivatives have been synthesized with substantial scores during in silico analyses, including molecular docking, molecular dynamics, and ADMET prediction tools. Acridine derivatives and N,4-disubstituted naphthylamines appear to interact significantly with 5-HT2A/C and MAO-A/B, respectively.(c) 2022 Elsevier B.V. All rights reserved.

Background and Aim: Chemotherapy is one of the most common methods available for the treatment of cancer. Resistance to anticancer drugs can result in failures in chemotherapy of cancers. Therefore, investigation is necessary for the discovery of new drugs. Homoisoflavonoids are well-known natural products that possess a wide range of pharmacological activities. Hence, synthesis and assessment of cytotoxicity of homoisoflavonoids containing morpholinoethoxy moiety and their molecular docking simulation were taken into consideration. Materials and Methods: Two 7-morpholinoethoxyhomoisoflavonoids synthesized via three steps including SN2 reaction of 7-hydroxychromanine with morpholino ethyl chloride hydrochloride in the basic media under reflux condition to produce intermediate 3. The second step included aldol condensation of the intermediate with suitable aldehydes in the presence of gaseous HCl in ethanol, and finally neutralization with NaOH 5%. The structures of the products were confirmed using IR, 13CNMR, and 1HNMR techniques. Cytotoxic effects of final products on HT-29 and 3T3 cell lines were assessed. To evaluate the binding mode of compounds with tubulin protein, docking simulation was performed by using MOE. Results: Two morpholinoethoxy homoisiflavonoids were prepared with moderate to good production yield. Cytotoxic evaluation of these compounds showed satisfactory results. The results of molecular docking simulation showed an acceptable binding energy of the interaction between the ligands with the tubulin protein binding site: (E)-7-(2-morpholinoethoxy)-3-(3,4,5-trimethoxybenzylidene) chroman-4-one= -7.3727 Kcal/mol and (E)-3-(4-methoxybenzylidene)-7-(2-morpholinoethoxy) chroman-4-one released -7.6838 Kcal/mol per mole of energy. Conclusion:The results showed that compound (E)-3-(4-methoxybenzylidene)-7-(2-morpholinoethoxy) chroman-4-one has higher cytotoxicity than (E)-7-(2-morpholinoethoxy)-3-(3,4,5-trimethoxybenzylidene) chroman-4-one against HT-29 and 3T3 cell lines. The in-silico results confirmed the results obtained from in vitro experiments and showed three interactions between ligand (E)-3-(4-methoxybenzylidene)-7-(2-morpholinoethoxy)chroman-4-one and αThr179, αThr145, and αTyr224 amino acids in tubulin active site.

Dementia is currently one of the leading causes of mortality globally, and mortality due to dementia will likely increase in the future along with corresponding increases in population growth and population aging. However, large inconsistencies in coding practices in vital registration systems over time and between countries complicate the estimation of global dementia mortality.

In recent decades, safe green synthetic approaches have attracted much interest from chemists.1–3 Running chemical reactions in safe and non-toxic media, such as water, is one of these approaches, ...

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a rules-based synthesis of the available evidence on levels and trends in health outcomes, a diverse set of risk factors, and health system responses. GBD 2019 covered 204 countries and territories, as well as first administrative level disaggregations for 22 countries, from 1990 to 2019. Because GBD is highly standardised and comprehensive, spanning both fatal and non-fatal outcomes, and uses a mutually exclusive and collectively exhaustive list of hierarchical disease and injury causes, the study provides a powerful basis for detailed and broad insights on global health trends and emerging challenges. GBD 2019 incorporates data from 281 586 sources and provides more than 3.5 billion estimates of health outcome and health system measures of interest for global, national, and subnational policy dialogue. All GBD estimates are publicly available and adhere to the Guidelines on Accurate and Transparent Health Estimate Reporting. From this vast amount of information, five key insights that are important for health, social, and economic development strategies have been distilled. These insights are subject to the many limitations outlined in each of the component GBD capstone papers.

In the present review, we summarized the applications of magnetic spinel ferrite nanoparticles as catalysts in organic reactions and transformations. Catalytic applications are comprised of using mostly cobalt, nickel, copper, and zinc ferrites, along with their mixed-metal combinations based on nano ferrites. The spinel ferrites (SFs) are gained principally by wet-chemical, sol-gel or co-precipitation methods, more infrequently by the mechanical high-energy ball milling, spark plasma sintering, sonochemical technique, microwave heating or hydrothermal route. Catalytic processes with the application of ferrite nanoparticles are included decomposition (in particular photocatalytic), reactions of dehydrogenation, oxidation, alkylation, CC coupling, removing organic/inorganic contaminants from aqueous solutions. As significant and remarkable advantages, ferrite nanocatalysts not only are environmentally benign and compatible with green chemistry aspects but also can be simply recovered from reaction systems and recycled up to several times almost without significant loss of their catalytic activity.

: Alzheimer, a progressive disease, is a common term for memory loss which interferes with daily life through severe influence on cognitive abilities. Based on the cholinergic hypothesis, and Xray crystallographic determination of the structure of acetylcholinesterase (AChE) enzyme, the level of acetylcholine (ACh, an important neurotransmitter associated with memory) in the hippocampus and cortex area of the brain has a direct effect on Alzheimer. This fact encourages scientists to design and synthesize a wide range of acetylcholinesterase inhibitors (AChEIs) to control the level of ACh in the brain, keeping in view the crystallographic structure of AChE enzyme and drugs approved by the Food and Drug Administration (FDA). : AChEIs have slightly diverse pharmacological properties, but all of them work by inhibiting the segregation of ACh by blocking AChE. We reviewed significant scaffolds introduced as AChEIs. In some studies, the activity against butyrylcholinesterase (BuChE) has been evaluated as well because BuChE is a similar enzyme to neuronal acetylcholinesterase and is capable of hydrolyzing ACh. In order to study AChEIs effectively, we divided them structurally into 12 classes and briefly explained effective AChEIs and compared their activities against AChE enzyme.

A novel, nano-sized, bis(3-(piperazine-1-yl)propyl)tungstate (BPPT) is introduced as an efficient and reusable organometallic catalyst which is considered as a heterogeneous Bronsted-Lowry base and applied successfully for one-pot synthesis of methyl 2-amino-4-aryl substituted-4H-chromene derivatives with good to excellent yields. BPPT has been prepared via a two-step route from natrium tungstate salt. At first, the oxygens of Na2WO4 react with 1-bromo-3-chloropropane via nucleophilic substitution to produce bis(3-choloro propyl)tungstate. Then nucleophilic substitution of piperazine with chlorines produced bis(3-(piperazine-1-yl)propyl) tungstate. Bis(3-(piperazine-1-yl)propyl) tungstate, which was called BPPT, characterized by fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), thermal gravimetric analysis (TGA), transmission electron microscopy (TEM) and scanning electron microscope (SEM). The catalyst is heterogeneous, green and recyclable. It is a thermally stable and its handling is easy. Its catalytic activity is very high and leads to the production of 4H-pyran derivatives with good to excellent yields in short reaction times. Furthermore, molecular modeling studies and ADMETox prediction revealed that not only it can inhibit acetylcholinesterase enzyme and act as an anti-Alzheimer agent but also has no variation from Lipinski's rule of five and can be a good candidate as anti-Alzheimer agents. These above-mentioned facts can be countered as advantages of the current protocol.

A series of novel chroman‐4‐one derivatives were designed and synthesized successfully with good to excellent yield (3a–l). In addition, the obtained products were evaluated for their cholinesterase (ChE) inhibitory activities. The results show that among the various synthesized compounds, analogs bearing the piperidinyl ethoxy side chain with 4‐hydroxybenzylidene on the 3‐positions of chroman‐4‐one (3l) showed the most potent activity with respect to acetylcholinesterase (anti‐AChE activity; IC50 = 1.18 μM). In addition, the structure–activity relationship was studied and the results revealed that the electron‐donating groups on the aryl ring of the 3‐benzylidene fragment (3k, 3l) resulted in the designed compounds to be more potent ChE inhibitors in comparison with those having electron‐withdrawing groups (3h). In this category, the strongest ChE inhibition was found for the compound containing piperidine as cyclic amine, and a hydroxyl group (for AChE, compound 3l) and fluoro group (for butyrylcholinesterase (BuChE, compound 3i) on the para‐position of the aryl ring of the benzylidene group. The molecular docking and dynamics studies of the most potent compounds (3i and 3l against BuChE and AChE, respectively) demonstrated remarkable interactions with the binding pockets of the ChE enzymes and confirmed the results obtained through in vitro experiments.

An adapted one-pot route to nanocatalyst-assisted synthesis of 4H-chromenes via three component condensation reaction between dimedone, malononitrile, and a broad range of aryl aldehydes by the use of magnetic nickel ferrite nanoparticles is described. By this achievement, not only a novel route to highly efficient synthesis of these series of heterocycles was introduced but also the scope of these medicinally important products was developed via preparation of some novel products. Above all, a new application of nickel ferrite nanoparticles (NiFe2O4 NPs) as highly efficient, green and magnetically recyclable catalyst has been introduced. Overall, obtaining good to excellent yields of products, environmentally and economic benign procedure, easy handling, availability of starting materials, use of non-toxic solvents, and high recyclability of nano-catalyst could be countered as most important advantages of this methodology.

An efficient, borax-catalyzed protocol for the synthesis of novel 4-aryl-substituted-4H-pyran derivatives fused to α-pyrone ring in a one-pot is described. By this achievement, some novel 4-aryl substituted 4H-pyrans fused to the α-pyrone ring as potential acetylcholinesterase inhibitors (AChEIs) with good to excellent yields are obtained from a one-pot three-component reaction between various aryl aldehydes, 4-hydroxy-6-methyl-2H-pyran-2-one and malononitrile. The method is a facile, inexpensive, practical and highly efficient one to obtain target compounds. The chemical structures of all compounds were characterized by FT-IR, FT-13CNMR and FT-1HNMR, MS spectroscopy and also elemental analyses data. Furthermore, the purity of all novel compounds was checked by HPLC. In addition, both molecular modelling studies and Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMETox) prediction nominated all compounds as good acetylcholinesterase inhibitors to the potential treatment of Alzheimer, Parkinson and Autism diseases that among them compound 4f showed the best activity against acetylcholinesterase enzyme.

This work reports an adapted route to the highly efficient synthesis of arylidene ethyl cyanoacetate derivatives in the presence of catalytic amounts of molybdenum oxide nanoparticles (MoO₃ NPs) under green conditions at ambient temperature. From the reaction, a wide range of novel arylidene ethyl cyanoacetates was successfully synthesized with high yields from the Knoevenagel condensation reaction between various aryl aldehydes and ethyl cyanoacetate in the presence of MoO₃ nanoparticles. The capability of catalyst to separate from the reaction mixture and then reuse is another advantage of this reaction. Furthermore, obtained products belong to analogous of organic compounds that have shown biological activity, and can be used pharmaceutics.

Acetylcholinesterase (AChE) catalyzes the conversion of Aβ peptide to its aggregated form and the peripheral anionic site (PAS) of AChE is mainly involved in this phenomenon. Also catalytic active site (CAS) of donepezil stimulates the break-down of acetylcholine (ACh) and depletion of ACh in cholinergic synapses are well established in brains of patients with AD. In this study, a set of compounds bearing phenoxyethyl amines were synthesized and their inhibitory activity toward electric eel AChE (eeAChE) and equine butyrylcholinesterase (eqBuChE) were evaluated. Molecular dynamics (MD) was employed to record the binding interactions of best compounds against human cholinesterases (hAChE and hBuChE) as well as donepezil as reference drug. In vitro results revealed that compound 5c is capable of inhibiting eeAChE activity at IC50 of 0.50 µM while no inhibitory activity was found for eqBuChE for up to 100 µM concentrations. Compound 5c, also due to its facile synthesis, small structure and high selectivity for eeAChE would be very interesting candidate in forthcoming studies. The main interacting parts of compound 5c and compound 7c (most potent eeAChE and eqBuChE inhibitors respectively) with receptors which confer selectivity for AChE and BuChE inhibition were identified, discussed, and compared with donepezil’s interactions. Also during MD simulation it was discovered for the first time that binding of substrates like donepezil to dual CAS and PAS or solely CAS region might have a suppressive impact on 4-α-helical bundles near the tryptophan amphiphilic tetramerization (WAT) domain of AChE and residues which are far away from AChE active site. The results proposed that residues involved in donepezil interactions (Trp86 and Phe295) which are located in CAS and mid-gorge are the mediator of conformational changes in whole protein structure.

Background: An efficient, promoted tri-component catalytic reaction between barbituric acid (or N,N-dimethyl barbituric acid), 4-hydroxy coumarin, and a wide range of aryl aldehydes using zinc oxide nanowires (ZnO NWs) to obtain some new 4-hydroxychromenylarylmethyl-6-hydroxypyrimidine-2,4-diones is described. Method: The reactants were successfully condensed via three C-C bond formation by zinc oxide nanowires (ZnO NWs) as an efficient, environmentally safe and recyclable nano catalyst to produce target molecules. In addition, the biological effects of synthesized products by the use of DPPH and acyclovir as positive controls and also Hep-2, vero cell, HSV-1, and adenovirus as four applied cell lines have been evaluated. Results: The results showed that synthesized products have anti-oxidant, cytotoxic and anti-viral activities and can offer promising prospect as biologically active agents. Conclusion: This achievement in an efficient and eco-friendly synthesis of novel analogous of hybrid molecules in aqueous media with special biological properties may engross chemists and pharmacologists as well as pharmacists in future.

A green cascade three-component reaction between 4-hydroxycoumarin, malononitrile and a wide range of arylaldehydes by employing molybdenum oxide nanoparticles (MoO 3 NPs) is described. By this achievement, some medicinally important products have been successfully synthesized in a one-pot under green conditions. Obtaining good to excellent yields of products, environmentally benign procedure, being easily handled, availability of starting materials, use of non-toxic solvents, and high recyclability of nano-catalysts are the most important advantages of this methodology.

An efficient and ultrasound-assisted route to the synthesis of arylidene malononitriles/methylciano- or ethylciano acetates in a one pot reaction catalyzed by silica sodium carbonate nanoparticles (SSC NPs) is described. In this reaction, SSC NPs demonstrated high efficiency as catalyst to obtain target products. By this achievement, a wide range of alpha,beta-unsaturated compounds as Knoevenagel condensation products with good to excellent yields are obtained from reaction between numerous arylaldehydes, and malononitrile, methyl cianoacetate or ethyl cianoacetate. Target products which prepared in high yield and high purity can be candidate as important biologically active molecules. This method is an easy, cheap, rapid and highly efficient for the synthesis of desired products. In addition, capability of catalyst to separate from reaction mixture and reuse in further runs and being compatible with green chemistry are considered as other advantages of this procedure. All products were deduced from their FT-IR and FT-NMR spectroscopic and elemental analysis data.

An efficient, promoted three-component (2+1) catalytic reaction between 3-methyl-1-phenyl-2-pyrazolin-5-one and arylglyoxal derivatives is described by the use of zinc oxide nanowires (ZnO NWs) as a green catalyst. By this achievement, some newly prepared bis(pyrazolyl)methane derivatives containing an aroyl group have been obtained. Starting materials were successfully condensed to obtain target products via three C–C bond formation in the presence of ZnO NWs as an efficient, cost-effective, environmentally friendly, and recyclable nanocatalyst. All synthesized products were obtained with good to excellent yields, and their structures were deduced by FTIR, 1H NMR, and 13C NMR spectroscopies and CHNS elemental analyses. It was shown that ZnO NWs can be separated, recovered after each run, and reused in further cycles (up to six runs) without significant loss of activity.

In this work, an efficient and green protocol for the synthesis of newly prepared acyl-substituted bis(pyrazolyl)methane derivatives has been introduced via a one-pot, three-component (2 + 1) condensation reaction by the use of 3-methyl-1-phenyl-2-pyrazolin-5-one, arylglyoxal derivatives, and silica sodium carbonate (SSC) as a recyclable green catalyst. All synthesized products were obtained with good to excellent yields, and their structures were deduced by FT-IR, 1H NMR, 13C NMR spectroscopies, and (C, H, N, S) elemental analyses. The capability of SSC to be reused can be considered as one of this procedure’s advantages. The studies on the reusability of catalyst revealed that SSC can efficiently catalyze this condensation reaction up to six times without significant loss of activity.