Carbon nanofiber/taurine-catalyzed synthesis of coumarin and 1,2,4,5-tetra-substituted imidazole derivatives under metal-free conditions.

The main subject of this research is the development of a suitable, efficient, and biocompatible carbon nanofiber-based catalytic system for the synthesis of coumarin and 1,2,4,5-tetra-substituted imidazoles. Brønsted acid carbon nanofiber/taurine catalyst was made during three steps: acid treatment, acylation, and then amination. The basic principles and general advantages of the synthesis method are elaborated. The acidity of the prepared nano-catalyst was investigated using the Hammet acidity technique and UV-Vis spectroscopy, and the H0 value for 5 × 10-2 mg/mL of CNF/T in 0.3 mM 4-nitroaniline solution was determined to be 1.47. The structure of the catalyst was successfully characterized using FT-IR, TGA, FESEM, XRD, TEM, EDX, EDS-MAP, BET, and XPS techniques. Here, we report the ability of carbon nanofiber/taurine as a Brønsted acid catalyst for the synthesis of coumarins and 1,2,4,5-tetra-substituted imidazole through a metal-free, cost-effective, and biocompatible multicomponent route. Among the advantages of this protocol are reaction time, excellent efficiency, reusability, and high activity of the catalyst.

Sb(iii)/Gum Arabic composite as a new natural-based environmentally green catalyst for the one-pot pseudo-four-component synthesis of 2H-indazolo[2,1-b] phthalazinetriones.

Sb(iii)-Gum Arabic composite as a unique natural-based and nontoxic catalyst was synthesized and characterized by FT-IR, XRD, TGA, ICP, BET, EDX and mapping. A four-component reaction of phthalic anhydride, hydrazinium hydroxide, aldehyde, and dimedone has been carried out in the presence of Sb(iii)/Gum Arabic composite to synthesise 2H-indazolo[2,1-b] phthalazine triones. The advantages of the present protocol are the appropriate reaction times, eco-friendly nature and high yields.

Synthesis of bis-spiro piperidines using nano γ-alumina supported Sb(v) under ultrasonic irradiation at room temperature conditions.

Group VA metalloid ion Lewis acids, Sb(v) was identified as a highly potent catalyst for the one-pot three-component synthesis of bis-spiro piperidine derivatives. The reaction was performed using amines, formaldehyde, and dimedone under ultrasonic irradiation at room temperature. The strong acidic property of the nano γ-alumina supported antimony(v) chloride plays a key role in accelerating the rate of the reaction and initiates the reaction smoothly. The heterogeneous nanocatalyst was fully characterized by FT-IR spectroscopy, XRD, EDS, TGA, FESEM, TEM, and BET techniques. Also, the structures of the prepared compounds were characterized by 1H NMR and FT-IR spectroscopies.

Fe3O4@nano-almondshell/Si(CH2)3/2-(1-piperazinyl)ethylamine as an effective magnetite almond shell-based nanocatalyst for the synthesis of dihydropyrano[3,2-c]chromene and tetrahydrobenzo[b]pyran derivatives.

The preparation and design of nano-catalysts based on magnetic biopolymers as green and biocompatible nano-catalysts have made many advances. This paper deals with the preparation of magnetite biopolymer-based Brønsted base nano-catalyst from a nano-almond (Prunus dulcis) shell. This magnetite biopolymer-based nano-catalyst was obtained through a simple process based on the core-shelling of nano-almond shell and Fe3O4 NPs and then the immobilization of 3-chloropropyltrimethoxysilane as linker and 2-aminoethylpiperazine as a basic section. Structural and morphological analysis of this magnetite biopolymer-based nano-catalyst were done using Fourier transform infrared spectroscopy, field emission scanning electron microscopy, X-ray diffraction, Thermogravimetric analysis, Vibrating sample magnetization, Energy-dispersive X-ray spectroscopy, Brunauer-Emmett-Teller, and Transmission electron microscopy techniques. The performance of the synthesized Fe3O4@nano-almondshell/Si(CH2)3/2-(1-piperazinyl)ethylamine as a novel magnetite biopolymer-based nano-catalyst for the synthesis of dihydropyrano[3,2-c]chromene and tetrahydrobenzo[b]pyran was investigated and showed excellent efficiency.

A green protocol ball milling synthesis of dihydropyrano[2,3-c]pyrazole using nano-silica/aminoethylpiperazine as a metal-free catalyst.

BACKGROUND: Ball mill is an effective, and green method for the synthesis of heterocyclic compounds in very good yields. This method is a simple, economical, and environmentally friendly process. In this work, an efficient approach for the synthesis of pyranopyrazoles (PPzs) using ball milling and metal-free nano-catalyst (Nano-silica/aminoethylpiperazine), under solvent-free conditions was reported. RESULTS: The new nano-catalyst silica/aminoethylpiperazine was prepared by immobilization of 1-(2-aminoethyl)piperazine on nano-silica chloride. The structure of the prepared nano-catalyst was identified by FT-IR, FESEM, TGA, EDX, EDS-map, XRD, and pH techniques. This novel nano-catalyst was used for the synthesis of dihydropyrano[2,3-c]pyrazole derivatives under ball milling and solvent-free conditions. CONCLUSIONS: Unlike other pyranopyrazoles synthesis reactions, this method has advantages including short reaction time (5-20 min), room temperature, and relatively high efficiency, which makes this protocol very attractive for the synthesis of pyranopyrazoles derivatives.

One-pot synthesis of naphtho[1,2-e][1,3]oxazines in the presence of FNAOSiPAMP*/CuII as an almond shell based nanocatalyst.

In the present research work, a novel catalyst based on natural material, namely, Fe3O4@nano-almondshell@OSi(CH2)3/NHCH2pyridine/CuII abbreviated (FNAOSiPAMP/CuII) was designed and prepared. The properties of the catalyst was identified by Fourier-transform infrared spectroscopy (FT-IR), Thermogravimetry ananlysis (TG), X-ray diffraction (XRD), Energy-dispersive X-ray spectroscopy (EDS), Field emission scanning electron microscopy (FESEM), Transmission electron microscopy (TEM), and Mapping. Furthermore, the evaluation of catalytic activity was done in the course of naphtho-1,3-oxazines synthesis. Solvent-free conditions, simplicity of operation, easy work-up and use of an eco-friendly catalyst are some of advantages of this protocol.

Novel Coumarin-Pyridine Hybrids as Potent Multi-Target Directed Ligands Aiming at Symptoms of Alzheimer's Disease.

In this research, a series of coumarin-based scaffolds linked to pyridine derivatives via a flexible aliphatic linkage were synthesized and assessed as multifunctional anti-AD agents. All the compounds showed acceptable acetylcholinesterase (AChE) inhibition activity in the nanomolar range (IC50 = 2-144 nM) and remarkable butyrylcholinesterase (BuChE) inhibition property (IC50 = 9-123 nM) compared to donepezil as the standard drug (IC50 = 14 and 275 nM, respectively). Compound 3f as the best AChE inhibitor (IC50 = 2 nM) showed acceptable BuChE inhibition activity (IC50 = 24 nM), 100 times more active than the standard drug. Compound 3f could also significantly protect PC12 and SH-SY5Y cells against H2O2-induced cell death and amyloid toxicity, respectively, superior to the standard drugs. It could interestingly reduce ß-amyloid self and AChE-induced aggregation, more potent than the standard drug. All the results suggest that compound 3f could be considered as a promising multi-target-directed ligand (MTDL) against AD.

Preparation and application of FNAOSiPPEA/Cu(II) as a novel magnetite almondshell based Lewis acid-Bronsted base nano-catalyst for the synthesis of pyrimidobenzothiazoles.

BACKGROUND: The magnetic nano-catalysts improve the contact between substrates and catalyst considerably and simple isolation of catalyst from reaction mixture. In this study, Fe3O4@nano-almondshell@OSi(CH2)3/2-(1-piperazinyl)ethylamine/Cu(II) abbreviated (FNAOSiPPEA/Cu(II)), was prepared, characterized and applied for the synthesis of 4H-pyrimido[2,1-b]benzothiazole. RESULTS: FNAOSiPPEA/Cu(II) as a bio-based nano-catalyst was prepared from the complexation of copper on 2-(1-piperazinyl)ethylamine, which was immobilized on Fe3O4@nano-almondshell@OSi(CH2)3 section. This new heterogeneous bifunctional Lewis acid/Bronsted base catalyst (FNAOSiPPEA/Cu(II)) was characterized by various techniques such as FT-IR, FESEM, TGA, EDS-MAP, XRD, VSM, BET, TEM, and XPS. So, the catalytic performance of this recyclable nano-catalyst was determined to promote the synthesis of 4H-pyrimido[2,1-b]benzothiazole derivatives at 100 °C under solvent-free conditions. CONCLUSIONS: Magnetite nano-catalyst of (FNAOSiPPEA/Cu(II)) is easily separated by an external magnet and successfully reused up at least 3 times with a slight loss of yield of the desired product.

Catalyst-free synthesis of tetrahydrodipyrazolopyridines via an one-pot tandem and green pseudo-six-component reaction in water.

BACKGROUND: A new, green and environmentally friendly protocol has been developed for the synthesis of tetrahydrodipyrazolopyridine derivatives. The structures of these products were determined in terms of melting point, FTIR, NMR and Mass spectroscopy. RESULTS: The tetrahydrodipyrazolopyridine derivatives were synthesized in water through a catalyst-free pseudo-six-component reaction of hydrazine hydrate, ethyl acetoacetate, ammonium acetate and aldehyde at room temperature. CONCLUSIONS: This novel procedure has some advantages such as aqueous media, high yield and simple work-up.

Nano-SiO2/DBN: an efficacious and reusable catalyst for one-pot synthesis of tetrahydrobenzo[b]pyran derivatives.

BACKGROUND: The nano-sized particles enhance the exposed surface area of the active part of the catalyst, thereby increasing the contact between precursors and catalyst considerably. In this study, nano-SiO2/1,5-diazabicyclo[4.3.0]non-5-en was synthesized, characterized and used as a heterogeneous nanocatalyst for the synthesis of tetrahydrobenzo[b]pyran derivatives. Fourier Transform Infrared Spectroscopy, Field Emission Scanning Electron Microscopy, Brunauer-Emmett-Teller plot, Energy Dispersive X-ray Spectroscopy and Thermo Gravimetric Analysis were used to discern nano-SiO2/1,5-diazabicyclo[4.3.0]non-5-en. RESULTS: Tetrahydrobenzo[b]pyrans were synthesized by using nano-SiO2/1,5-diazabicyclo[4.3.0]non-5-en via one-pot three-component condensation of malononitrile, aldehydes and dimedone in H2O/EtOH at 60 °C. The results indicate that tetrahydrobenzo[b]pyrans were synthesized in good to high yields and short reaction times. CONCLUSIONS: The fundamental privileges of this method are short reaction time, plain procedure, recyclability of catalyst and high yields of products.

Rapid four-component synthesis of dihydropyrano[2,3-c]pyrazoles using nano-eggshell/Ti(IV) as a highly compatible natural based catalyst.

Nano-eggshell/Ti(IV) as a novel naturally based catalyst was prepared, characterized and applied for the synthesis of dihydropyrano[2,3-c]pyrazole derivatives. The characterization of nano-eggshell/Ti(IV) was performed using Fourier Transform Infrared spectroscopy, X-ray Diffraction, Field Emission Scanning Electron Microscopy, Energy-Dispersive X-ray Spectroscopy, and Thermo Gravimetric Analysis. Dihydropyrano[2,3-c]pyrazoles were synthesized in the presence of nano-eggshell/Ti(IV) via a four component reaction of aldehydes, ethyl acetoacetate, malononitrile and hydrazine hydrate at room temperature under solvent free conditions. The principal affairs of this procedure are mild condition, short reaction times, easy work-up, high yields, reusability of the catalyst and the absence of toxic organic solvents.

Docking, Synthesis and Evaluation of the Antifungal Activity of Pyrimido [4,5-b]quinolins.

In order to expand the application of Fe3O4@SiO2-SnCl4 in the synthesis of heterocyclic compounds, in this study, we wish to report the use of one-pot three component synthesis of pyrimido [4,5-b]quinolone derivatives ( D1-D16 ) through reaction of 6-amino-2-(methylthio)pyrimidin-4 (3H)-one, dimedone, or 1,3-cyclohexadione and aldehydes in the presence of Fe3O4@SiO2-SnCl4 as an efficient eco-friendly catalyst under ultrasound irradiation. The final aim of this study is evaluation of antifungal activity of resulted products. Synthesis of pyrimido [4,5-b]quinolin derivatives were done via three components coupling reaction of aldehyde, dimedone or 1,3-cyclohexadione and 6-amino-2-(methylthio)pyrimidin-4 (3H)-one in the presence of Fe3O4@SiO2-SnCl4 under ultrasonic irradiation in water at 60 °C. The products structure were studied by FT-IRI, 1H NMR,II and 13C NMRII. All the compounds were screened for antimicrobial activity by broth microdilution methods as recommended by CLSIIII. Considering our results showed that compound ( D13 ) had the most antifungal activity against C. dubliniensis, C. Albicans, C. Tropicalis, and C. Neoformance at concentrations ranging (MIC90) from 1-4 µg/mL. Compounds ( D9 ), ( D10 ), ( D14 ), and ( D15 ) had significant inhibitory activities against C. dubliniensis at concentrations ranging (MIC90) from 4-8 µg/mL, respectively. 5-(3,4-dihydroxyphenyl)-8,8-dimethyl-2-(methylthio)-5,8,9,10-tetrahydropyrimido[4,5-b]quinoline-4,6(3H,7H)-dione ( D13 ) exhibited inhibitory and fungicidal activities against the tested yeasts. The specific binding mode or the binding orientation of more efficient compounds to CYP51 active site, have been also performed by molecular modeling investigations and showed that there is a good correlation with biological test.

Cancer Treatment by Caryophyllaceae-Type Cyclopeptides.

Cancer is one of the leading diseases, which, in the most cases, ends with death and, thus, continues to be a major concern in human beings worldwide. The conventional anticancer agents used in the clinic often face resistance among many cancer diseases. Moreover, heavy financial costs preclude patients from continuing treatment. Bioactive peptides, active in several diverse areas against man's health problems, such as infection, pain, hypertension, and so on, show the potential to be effective in cancer treatment and may offer promise as better candidates for combating cancer. Cyclopeptides, of natural or synthetic origin, have several advantages over other drug molecules with low toxicity and low immunogenicity, and they are easily amenable to several changes in their sequences. Given their many demanded homologues, they have created new hope of discovering better compounds with desired properties in the field of challenging cancer diseases. Caryophyllaceae-type cyclopeptides show several biological activities, including cancer cytotoxicity. These cyclopeptides have been discovered in several plant families but mainly are from the Caryophyllaceae family. In this review, a summary of biological activities found for these cyclopeptides is given; the focus is on the anticancer findings of these peptides. Among these cyclopeptides, information about Dianthins (including Longicalycinin A), isolated from different species of Caryophyllaceae, as well as their synthetic analogues is detailed. Finally, by comparing their structures and cytotoxic activities, finding the common figures of these kinds of cyclopeptides as well as their possible future place in the clinic for cancer treatment is put forward.

One-pot solvent-free synthesis of 2,3-dihydro-2-substituted-1H-naphtho[1,2-e][1,3]oxazine derivatives using Fe3O4@nano-cellulose/TiCl as a bio-based and recyclable magnetic nano-catalyst.

The present study describes an efficient and environmentally benign protocol for the synthesis of 2,3-dihydro-2-substituted-1H-naphtho[1,2-e][1,3]oxazine derivatives. Synthesis is done by one-pot three-component condensation of 2-naphthol, formaldehyde, and primary amines in the presence of Fe3O4@nano-cellulose/TiCl as a bio-based magnetic nano-catalyst under solvent-free conditions at room temperature grinding. This green procedure offers the advantages of high yield, short reaction time, environmental friendliness, easy workup, simple magnetic recovery of the catalyst and its reusability up to ten times without significant loss of catalytic activity. The structure of products was approved by FT-IR, 1H-NMR, 13C-NMR spectroscopy.

Synthesis and biological evaluation of new N-benzylpyridinium-based benzoheterocycles as potential anti-Alzheimer's agents.

A novel series of benzylpyridinium-based benzoheterocycles (benzimidazole, benzoxazole or benzothiazole) were designed as potent acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors. The title compounds 4a-q were conveniently synthesized via condensation reaction of 1,2-phenylenediamine, 2-aminophenol or 2-aminothiophenol with pyridin-4-carbalehyde, followed by N-benzylation using various benzyl halides. The results of in vitro biological assays revealed that most of them, especially 4c and 4g, had potent anticholinesterase activity comparable or more potent than reference drug, donepezil. The kinetic study demonstrated that the representative compound 4c inhibits AChE in competitive manner. According to the ligand-enzyme docking simulation, compound 4c occupied the active site at the vicinity of catalytic triad. The compounds 4c and 4g were found to be inhibitors of Aß self-aggregation as well as AChE-induced Aß aggregation. Meanwhile, these compounds could significantly protect PC12 cells against H2O2-induced injury and showed no toxicity against HepG2 cells. As multi-targeted structures, compounds 4c and 4g could be considered as promising candidate for further lead developments to treat Alzheimer's disease.

Nano-kaolin/Ti4+/Fe3O4: a magnetic reusable nano-catalyst for the synthesis of pyrimido[2,1-b]benzothiazoles.

Herein, nano-kaolin/Ti4+/Fe3O4 as a new magnetic nano-catalyst was synthesized, and its structural properties were characterized using various techniques such as Fourier transform infrared (FTIR) spectroscopy, field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), a vibrating sample magnetometer (VSM), thermogravimetric analysis (TGA) and energy-dispersive X-ray spectroscopy (EDX). This catalyst was used for the synthesis of pyrimido[2,1-b]benzothiazoles via the one-pot condensation of 2-aminobenzothiazole, an aldehyde and ß-keto ester under solvent-free conditions at 100 °C. This simple protocol has many advantages such as easy workup, high product yields, short reaction times and reusability of the catalyst.

Nano-SnCl4.SiO2, an efficient catalyst for synthesis of benzimidazole drivatives as antifungal and cytotoxic agents.

The concept of green chemistry has made significant impact on many frontages including the use of green solvents or sustainable catalyst materials. Benzimidazole ring is an important nitrogen-containing heterocyclic, which exhibits a broad spectrum of bioactivities and are widely utilized by the medicinal chemists for drug discovery. A simple and efficient method was developed for the synthesis of some benzimidazole derivatives via reaction of o-phenylenediamine and substituted aldehydes in the presence of nano-SnCl4/SiO2 as a mild catalyst. Ten 2-substituted benzimidazole compounds ( J1-J10 ) were synthesized. All compounds were evaluated against different species of yeasts and filament fungi using broth micro dilution method as recommended by clinical and laboratory standard institute. Among these compounds, the active ones were chosen for their cytotoxic activities evaluation against MCF-7 and A549 cell lines using MTT method. Compound J2 showed the best antifungal activity against all tested species. Compounds J5-J7 had also desirable antifungal activities. Our cytotoxic results were also similar to the antifungal activities except for J7 which had no cytotoxic activity.

Synthesis of Linear and Cyclic Disulfide Heptapeptides of Longicalycinin A and Evaluation of Toxicity on Cancerous Cells HepG2 and HT-29.

In this work, linear and cyclic disulfide heptapeptides of Longicalycinin A have been successfully synthesized by solid phase methodology with Fmoc /t-Bu and solution phase, respectively. 2-Chlorotrityl chloride resin (2-CTC) was used as a solid support. The synthesized linear disulfide analogue of Longicalycinin A was cleaved from the resin as a protected peptide. The final deprotection was performed by treatment with TFA 95% containing scavengers to achieve the deprotected linear disulfide analogue of Longicalycinin A which was characterized by different instrumental methods using LC-MS and FT-IR. Macrocyclization of deprotected linear peptide was done by an oxidating reagent. Linear and cyclic disulfide heptapeptides of Longicalycinin A were evaluated their toxic activity against cell lines of HepG2 and HT-29 using 3- (4, 5-dimethylthiazol-2-yl) -2, -5-diphenyltetrazolium bromide reagent in MTT assay. The synthetic analogues showed a relative good activity against cell lines of HepG2 and HT-29 with IC50 values from 10.33 µg/mL to 12.45 µg/mL, in comparison to the standard drug 5-fluorouracil (5-FU). Safety profiles of the synthesized linear and cyclic disulfide analogues of Longicalycinin A were also examined on skin fibroblast cells. Between the linear and cyclic disulfide heptapeptides of Longicalycinin A, the cyclic peptide showed a considerable toxic activity on the cancerous cell lines along with a low safety result on normal cells. Therefore, the linear disulfide heptapeptide of Longicalycinin A would be encouraging to develop new anticancer agents.