Platform-agnostic electrochemical sensing app and companion potentiostat.

Electrochemical sensing is ubiquitous in a number of fields ranging from biosensing, to environmental monitoring through to food safety and battery or corrosion characterisation. Whereas conventional potentiostats are ideal to develop assays in laboratory settings, they are in general, not well-suited for field work due to their size and power requirements. To address this need, a number of portable battery-operated potentiostats have been proposed over the years. However, most open source solutions do not take full advantage of integrated circuit (IC) potentiostats, a rapidly evolving field. This is partly due to the constraining requirements inherent to the development of dedicated interfaces, such as apps, to address and control a set of common electrochemical sensing parameters. Here we propose the PocketEC, a universal app that has all the functionalities to interface with potentiostat ICs through a user defined property file. The versatility of PocketEC, developed with an assay developer mindset, was demonstrated by interfacing it, via Bluetooth, to the ADuCM355 evaluation board, the open-source DStat potentiostat and the Voyager board, a custom-built, small footprint potentiostat based around the LMP91000 chip. The Voyager board is presented here for the first time. Data obtained using a standard redox probe, Ferrocene Carboxylic Acid (FCA) and a silver ion assay using anodic stripping multi-step amperometry were in good agreement with analogous measurements using a bench top potentiostat. Combined with its Voyager board companion, the PocketEC app can be used directly for a number of wearable or portable electrochemical sensing applications. Importantly, the versatility of the app makes it a candidate of choice for the development of future portable potentiostats. Finally, the app is available to download on the Google Play store and the source codes and design files for the PocketEC app and the Voyager board are shared via Creative Commons license (CC BY-NC 3.0) to promote the development of novel portable or wearable applications based on electrochemical sensing.

Synthesis and radioligand-binding assay of 2,5-disubstituted thiadiazoles and evaluation of their anticonvulsant activities.

In this study, a number of 2,5-disubstituted 1,3,4-thiadiazoles were synthesized using an appropriate synthetic route, and their anticonvulsant activity was determined by the maximal electroshock seizure (MES) test and their neurotoxicity was evaluated by the rotarod test. Additionally, their hypnotic activity was tested using the pentobarbital-induced sleep test. Compounds 7 (ED50 = 1.14 and 2.72 µmol/kg in the MES and sleep tests, respectively) and 11 (ED50 = 0.65 and 2.70 µmol/kg in the MES and sleep tests, respectively) were the most potent ones in the sleep test and anticonvulsant test, showing a comparable activity with diazepam as the reference drug. The results of in vivo studies, especially the antagonistic effects of flumazenil, and also the radioligand-binding assay confirmed the involvement of benzodiazepine (BZD) receptors in the anticonvulsant and hypnotic activity of compounds 7 and 11. Finally, the docking study of compound 11 in the BZD-binding site of the GABAA (gamma-aminobutyric acid) receptor confirmed the possible binding of the compound to the BZD receptors. We concluded that the novel 1,3,4-thiadiazole derivatives with appropriate substitution at positions 2 and 5 of the heterocyclic ring had a good affinity to BZD receptors and showed significant efficacy in the pharmacological tests.

Molybdenum Oxide Nanoparticles as Recyclable Heterogeneous Catalyst for Synthesis of Arylidene Ethyl Cyanoacetates.

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.

Design, synthesis, biological evaluation, and molecular dynamics of novel cholinesterase inhibitors as anti-Alzheimer's agents.

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.

Synthesis and cytotoxic activity of novel poly-substituted imidazo[2,1-c][1,2,4]triazin-6-amines.

A novel series of 3,4-diphenyl-7-(hetero)arylimidazo[2,1-c][1,2,4]triazin-6-amine derivatives were synthesized via three-component reaction of 5,6-diphenyl-1,2,4-triazin-3-amine, various aromatic aldehydes, and cyclohexyl isocyanide. All synthesized compounds were tested against HL60 (human promyelocytic leukemia), MOLT-4 (human T lymphoblastic leukemia), and MCF-7 (human breast adenocarcinoma) cell lines, as cytotoxic agents. The structure-activity relationships study revealed that the introduction of hydroxyl and methoxy groups on the 7-phenyl ring can modulate the cytotoxic activity of these compounds. Among the 7-aryl derivatives, 3-hydroxyphenyl and 3-hydroxy-4-methoxyphenyl derivatives (6h and 6o) were the most potent compounds against HL60 and MCF-7 cells (IC(50s) = 9.8 - 20.4 µM). However, the replacement of the 7-aryl moiety with pyridyl or furan-2-yl resulted in compounds 6p or 6r with more promising cytotoxicity against MOLT-4 cell line (IC50 values 12.1 and 13.0 µM, respectively). Also, the acridine orange/ethidium bromide staining assay in MCF-7 cells suggested that the cytotoxic activity of compound 6r occurs via apoptosis.

Amino-7,8-dihydro-4H-chromenone derivatives as potential inhibitors of acetylcholinesterase and butyrylcholinesterase for Alzheimer's disease management; in vitro and in silico study.

In this article, we present the design and synthesis of amino-7,8-dihydro-4H-chromenone derivatives as possible inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) for the management of Alzheimer's disease (AD). The target compounds were evaluated against AChE and BChE in vitro, and 4k exhibited good potency against BChE (IC50 = 0.65 ± 0.13 µM) compared with donepezil used as a positive control. Kinetic studies revealed that compound 4k exhibited a competitive-type inhibition with a Ki value of 0.55 µM. Molecular docking and molecular dynamics simulations further supported the rationality of our design strategy, as 4k showed promising binding interactions with the active sites of BChE. Overall, our findings highlight the potential of amino-7,8-dihydro-4H-chromenone derivatives as promising candidates for developing novel therapeutics targeting cholinesterase in managing AD.

5,6-Dimethoxybenzofuran-3-one derivatives: a novel series of dual Acetylcholinesterase/Butyrylcholinesterase inhibitors bearing benzyl pyridinium moiety.

BACKGROUND: Several studies have been focused on design and synthesis of multi-target anti Alzheimer compounds. Utilizing of the dual Acetylcholinesterase/Butyrylcholinesterase inhibitors has gained more interest to treat the Alzheimer's disease. As a part of a research program to find a novel drug for treating Alzheimer disease, we have previously reported 6-alkoxybenzofuranone derivatives as potent acetylcholinesterase inhibitors. In continuation of our work, we would like to report the synthesis of 5,6-dimethoxy benzofuranone derivatives bearing a benzyl pyridinium moiety as dual Acetylcholinesterase/Butyrylcholinesterase inhibitors. METHODS: The synthesis of target compounds was carried out using a conventional method. Bayer-Villiger oxidation of 3,4-dimethoxybenzaldehyde furnished 3,4-dimethoxyphenol. The reaction of 3,4-dimethoxyphenol with chloroacetonitrile followed by treatment with HCl solution and then ring closure yielded the 5,6-dimethoxy benzofuranone. Condensation of the later compound with pyridine-4-carboxaldehyde and subsequent reaction with different benzyl halides afforded target compounds. The biological activity was measured using standard Ellman's method. Docking studies were performed to get better insight into interaction of compounds with receptor. RESULTS: The in vitro anti acetylcholinesterase/butyrylcholinesterase activity of compounds revealed that, all of the target compounds have good inhibitory activity against both Acetylcholinesterase/Butyrylcholinesterase enzymes in which compound 5b (IC50 = 52 ± 6.38nM) was the most active compound against acetylcholinesterase. The same binding mode and interactions were observed for the reference drug donepezil and compound 5b in docking study. CONCLUSIONS: In this study, we presented a new series of benzofuranone-based derivatives having pyridinium moiety as potent dual acting Acetylcholinesterase/Butyrylcholinesterase inhibitors.

Virtual Flavor: High-fidelity simulation of real flavor experiences.

Food and drink are a key part of our lives. While Virtual Reality has the potential to provide high-fidelity simulation of real experiences in virtual worlds, the incorporation of flavor appreciation within these virtual experiences has largely been ignored. This paper introduces a virtual flavor device to simulate real flavor experiences. The goal is to provide virtual flavor experiences, using food safe chemicals for the three components of a flavor (taste, aroma, mouthfeel), which are perceived as "indistinguishable" from the equivalent real experience. Furthermore, because we are delivering a simulation, the same device can be used to take a user on a "flavor discovery journey" from a start flavor to a new, preferred flavor by adding or removing any amount of the components. In the first experiment, participants (N = 28) were exposed to real and virtual samples of orange juice, and the health product, rooibos tea, and asked to rate their similarity. The second experiment investigated how participants (N = 6) could move within "flavor space" from one flavor to another. The results show that it is possible to simulate, with a high degree of precision, a real flavor experience, and precisely controlled "flavor discovery journeys" can be undertaken using virtual flavors.

Exploring the potential of a novel phenoxyethyl piperidine derivative with cholinesterase inhibitory properties as a treatment for dementia: Insights from STZ animal model of dementia.

Alzheimer's disease (AD) is a neurodegenerative disease, often characterized by progressive deficits in memory and cognitive functions. Cholinesterase inhibitors have been introduced as promising agents to enhance cognition and memory in both human patients and animal models of AD. In the current study, we assessed the effects of a synthetic phenoxyethyl piperidine derivative, compound 7c, as a novel dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), on learning and memory, as well as serum and hippocampal AChE levels in an animal model of AD. The model of dementia was induced by intracerebroventricular injection of streptozotocin (STZ, 2 mg/kg) to male Wistar rats. STZ-treated rats received compound 7c (3, 30, and 300 µg/kg) for five consecutive days. ​Passive avoidance (PA) learning and memory, as well as spatial learning and memory using Morris water maze, were evaluated. The level of AChE was measured in the serum and the left and right hippocampus. Findings demonstrated that compound 7c (300 µg/kg) was able to reverse STZ-induced impairments in PA memory, while also reduced the increased AChE level in the left hippocampus. Taken together, compound 7c appeared to act as a central AChE inhibitor, and its role in alleviating cognitive deficits in the AD animal model suggests that it may have therapeutic potential in AD dementia. Further research is required to assess the effectiveness of compound 7c in more reliable models of AD in light of these preliminary findings.

Indole-carbohydrazide linked phenoxy-1,2,3-triazole-N-phenylacetamide derivatives as potent α-glucosidase inhibitors: design, synthesis, in vitro α-glucosidase inhibition, and computational studies.

BACKGROUND: A new series of indole-carbohydrazide-phenoxy-1,2,3-triazole-N-phenylacetamide hybrids 11a-o was designed based on molecular hybridization of the active pharmacophores of the potent α-glucosidase inhibitors. These compounds were synthesized and evaluated against α-glucosidase. METHODS: The 15 various derivatives of indole-carbohydrazide-phenoxy-1,2,3-triazole-N-phenylacetamide scaffold were synthesized, purified, and fully characterized. These derivatives were evaluated against yeast α-glucosidase in vitro and in silico. ADMET properties of the most potent compounds were also predicted. RESULTS: All new derivatives 11a-o (IC50 values = 6.31 ± 0.03-49.89 ± 0.09 µM) are excellent α-glucosidase inhibitors in comparison to acarbose (IC50 value = 750.0 ± 10.0 µM) that was used as a positive control. Representatively, (E)-2-(4-((4-((2-(1H-indole-2-carbonyl)hydrazono)methyl) phenoxy)methyl)-1H-1,2,3-triazol-1-yl)-N-(4-methoxyphenyl)acetamide 11d with IC50 = 6.31 µM against MCF-7 cells, was 118.8-times more potent than acarbose. This compound is an uncompetitive inhibitor against α-glucosidase and showed the lowest binding energy at the active site of this enzyme in comparison to other potent compounds. Furthermore, computational calculations predicted that compound 11d can be an orally active compound. CONCLUSION: According to obtained data, compound 11d can be a valuable lead compound for further structural development and assessments to obtain effective and potent new α-glucosidase inhibitors.

Design, synthesis and biological assessment of new 1-benzyl-4-((4-oxoquinazolin-3(4H)-yl)methyl) pyridin-1-ium derivatives (BOPs) as potential dual inhibitors of acetylcholinesterase and butyrylcholinesterase.

Alzheimer's disease (AD), is among the most growing neurodegenerative diseases, which is mainly caused by the acetylcholine neurotransmitter loss in the hippocampus and cortex. Emerging of the dual Acetylcholinesterase (AChE)/Butyrylcholinesterase (BuChE) inhibitors has increased for treating Alzheimer disease. In this study, we would like to report the design and synthesis of a new sequence of 1-benzyl-4-((4-oxoquinazolin-3(4H)-yl)methyl) pyridin-1-ium derivatives (BOPs) assessed as BuChE and AChE inhibitors. Ellman's approach was used for the evaluation of AChE and BuChE inhibitory activities. Moreover, docking research was conducted to predict the action mechanism. Among all synthesized compounds, 1-(3-bromobenzyl)-3-((4-oxoquinazolin-3(4H)-yl)methyl) pyridin-1-ium bromide (BOP-1) was found to be the most active compound with dual activity for inhibition of AChE (IC50 = 5.90 ± 0.07µM), and BuChE (IC50 = 6.76 ± 0.04µM) and 1-(4-chlorobenzyl)-3-((6,7-dimethoxy-4-oxoquinazolin-3(4H)-yl)methyl) pyridin-1-ium chloride (BOP-8) showed the highest AChE inhibitory activity (IC50s = 1.11 ± 0.09 µM). The synthesized compounds BOP-1 and BOP-8 could be proposed as valuable lead compounds for further drug discovery development against AD.

Microwave-assisted preparation of ZnFe2O4@methyl cellulose as a new nano-biomagnetic photocatalyst for photodegradation of metronidazole.

In the present study, ZnFe2O4@methyl cellulose (MC) nano-biomagnetic photocatalyst was rapidly prepared based on a microwave-assisted method. FTIR, FESEM, EDS, UV-DRS, XRD, and VSM were performed to characterize the structure of as-prepared ZnFe2O4@MC. The removal efficiency of Metronidazole (MNZ) degradation was 92.65% and 71.12% in synthetic and real samples under optimal conditions, respectively. The removal efficiency of TOC was also reported to be 77.87% under optimal conditions. The kinetic linear models showed that the photocatalytic degradation of MNZ follows either a pseudo-first-order kinetic or the Langmuir-Hinshelwood model. The correlation coefficients (R2) were 0.92, 0.97, 0.99, and 0.94, respectively at 5, 10, 20, and 30 mg/L. The equilibrium adsorption coefficient (KL-H) of the Langmuir-Hinshelwood model and the superficial reaction rate constant (Kc) were 0.633 Lmg-1 and 0.203 mg/L min-1, respectively. The participation of active species such as holes and hydroxyl and superoxide radicals was studied during MNZ photodegradation with organic and inorganic radical scavengers. Finally, the nano-biomagnetic catalyst could be reused for six further runs without remarkable changes in catalytic efficiencies. In this study, we present a new magnetic nanocomposite and a novel strategy for antibiotic removal from aqueous media.

The efficacy of a traditional medicine preparation on second-degree burn wounds in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Lime Salve (L.S) has been well documented from the 9th to the 19th century AD by traditional Iranian medicine (TIM) as an effective remedy for burn healing. AIM OF THE STUDY: The present study was undertaken to evaluate the healing effect and related underlying mechanisms of Lime Salve in a model of deep second-degree thermal burn in male Wistar rats. MATERIALS AND METHOD: L.S was made up of a combination of refined calcium hydroxide powder, beeswax and sesame oil and its quality control was assessed. A deep second-degree burn was created by a hot plate in 48 male Wistar rats. Afterwards, they were randomly divided into four groups including normal saline (C group), L.S (T group), basement of formulation composed of beeswax and sesame oil (B group) and silver sulfadiazine (S group). On days 5, 10, 17 and 24, the wounds were digitally photographed by a camera and after sacrifice of the rats, skin samples were obtained for performing qRT-PCR, immunohistochemistry staining and histological examination. RESULTS: L.S prominently augmented the wound closure rate, neovascularization on day 10 and collagen formation on days 17 and 24 in comparison with the C group. Furthermore, the Salve-exposed specimens showed a significant higher epithelialization during the experiment with a peak on day 24. qRT-PCR also showed that on day 10, VEGF and TGF-ß1 genes were significantly higher in the T group as compared with the C group. Also, MMP-9 and MMP-2 genes had a significant peak of expression on day 17 and rapid reduction of expression on day 24. Expression levels of IL-6 and TNF-α genes peaked on day 10 in the T group, followed by a progressive reduction until the end of the examination. CONCLUSION: L.S could effectively accelerate the healing process of deep second-degree burn wounds and therefore, it may be recommended as a promising topical medication for treating burn wounds in the future clinical trials.

Nickel Ferrite (NiFe2O4) Nanoparticles as Magnetically Recyclable Nanocatalyst for Highly Efficient Synthesis of 4H-Chromene Derivatives.

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.

Highly Significant Scaffolds to Design and Synthesis Cholinesterase Inhibitors as Anti-Alzheimer Agents.

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.

Synthesis, and molecular modeling of bis(3-(piperazine-1-yl)propyl)tungstate (BPPT) nanoparticles, and its first catalytic application for one-pot synthesis of 4H-chromene derivatives.

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 facile and green method for synthesis of ZnFe2O4@CMC as a new magnetic nanophotocatalyst for ciprofloxacin removal from aqueous media.

This study aimed to synthesize a ZnFe2O4@carboxymethyl cellulose (CMC) nanophotocatalyst using a simple, facile, and green hydrothermal method for ciprofloxacin (CIP) removal from aqueous solutions. At first, ZnFe2O4@CMC was synthesized using the hydrothermal method, and then it was characterized. To assay the photocatalytic activity of ZnFe2O4@CMC, its ability was investigated in CIP and total organic carbon (TOC) removal by considering the effect of some variables such as initial CIP concentrations (5-30 mg/L), pH (3-11), nanophotocatalyst loading (0.1-0.5 g), and reaction time (20-120 min). The kinetic performance of the process was assessed by the pseudo-first order and Langmuir-Hinshelwood models. The concentration of CIP and TOC in the samples was determined using high performance liquid chromatography and a TOC analyzer, respectively. The influence of competitive compounds was examined on the efficiency of the nanophotocatalyst through its application for a real wastewater sample. Moreover, the reusability and chemical stability of ZnFe2O4@CMC were studied. Advantages of this technique are as follows: •ZnFe2O4@CMC as a high potent magnetically separable photocatalyst is designed by a green, simple, and fast hydrothermal method.•ZnFe2O4@CMC displays significant photocatalytic activity in photocatalytic degradation processes for ciprofloxacin removal.•ZnFe2O4@CMC exhibits good chemical stability and reusability.

Phenoxyethyl Piperidine/Morpholine Derivatives as PAS and CAS Inhibitors of Cholinesterases: Insights for Future Drug Design.

Acetylcholinesterase (AChE) catalyzes the conversion of Aß 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.

Synthesis, biological evaluation, and computational studies of novel fused six-membered O-containing heterocycles as potential acetylcholinesterase inhibitors.

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.

Efficient drug delivery of ß-estradiol encapsulated in Zn-metal-organic framework nanostructures by microwave-assisted coprecipitation method.

Metal-organic frameworks (MOFs) are structures made up of inorganic nodes, which can be either single ions or clusters of ions and organic linkers. This study reports on a novel processing route for producing ß-estradiol encapsulated in Zn-MOF nanocomposites by microwave-assisted coprecipitation as a facile and fast method. Zn-MOF nanocomposites were synthesized with the aid of Zn(OAc)2⋅2H2O and 2,6-pyridine dicarboxylic acid ammonium as an organic ligand. Furthermore, we studied encapsulated ß-estradiol which is one of the most important classes of estrogenic compounds that are used in the treatment of prostate cancer and breast cancer. The effects of ß-estradiol concentration and microwave irradiation on the morphology, particle size, distribution, and in vitro photoluminescence spectroscopy experiments of ß-estradiol entrapped in Zn-MOF nanocomposites were characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy, and Brunauer-Emmett-Teller spectroscopy. These nanostructures can be a good option for thawing hydrophilic and hydrophobic drugs over time. Zn-MOF nanocomposites with high porosity, total pore volume (0.04665 cm3g-1), and nanostructures have provided the platform to load ß-estradiol such as low soluble drugs. Maximum of drug release was about 82% at pH 8.9 after 8 h.