Integration of plasmonic AgPd alloy nanoparticles with single-layer graphitic carbon nitride as Mott-Schottky junction toward photo-promoted H2 evolution.

Plasmonic AgPd alloy nanoparticles (AgPdNPs) decorated on single-layer carbon nitride (AgPdNPs/SLCN) for the designing of the Mott-Schottky junction were constructed with the ultrasonically assisted hydrothermal method and used toward photo evolution H2 from formic acid (FA) at near room temperature (30 °C). The Pd atom contains active sites that are synergistically boosted by the localized surface plasmon resonance (LSPR) effect of Ag atoms, leading to considerably enhanced photocatalytic properties. The photoactive AgPdNPs/SLCN obtained supreme catalytic activity to produce 50 mL of gas (H2 + CO2) with the initial turnover frequency of 224 h-1 under light irradiation. The catalyst showed stable catalytic performance during successive cycles.

Single-pot tandem oxidative/C-H modification amidation process using ultrasmall PdNP-encapsulated porous organosilica nanotubes.

Herein, we studied a single-pot method with a dual catalysis process towards the conversion of primary aromatic alcohols to amides using ultrasmall PdNPs of controlled uniform size (1.8 nm) inside hybrid mesoporous organosilica nanotubes (MO-NTs). The catalyst exhibited excellent performance in water under mild conditions and showed high stability. The catalytic activity towards the tandem oxidation of alcohols in the presence of amine salts and H2O2 to their corresponding amides without producing byproducts was evaluated, and high yields were obtained for all products. The structure of the organosilica nanotubes containing palladium nanoparticles was investigated using various characterization techniques such as XRD, TEM, BET, solid-state 29Si NMR and solid-state 13C CP MAS NMR. Catalyst recycling tests showed that the catalytic power of PdNPs@B-SNTs was preserved after 8 cycles and a slight decrease in catalyst activity was observed.

Novel Coumarin Containing Dithiocarbamate Derivatives as Potent α-Glucosidase Inhibitors for Management of Type 2 Diabetes.

BACKGROUND: α-Glucosidase is a hydrolyzing enzyme that plays a crucial role in the degradation of carbohydrates and starch to glucose. Hence, α-glucosidase is an important target in carbohydrate mediated diseases such as diabetes mellitus. OBJECTIVE: In this study, novel coumarin containing dithiocarbamate derivatives 4a-n were synthesized and evaluated against α-glucosidase in vitro and in silico. METHODS: These compounds were obtained from the reaction between 4-(bromomethyl)-7- methoxy-2H-chromen-2-one 1, carbon disulfide 2, and primary or secondary amines 3a-n in the presence of potassium hydroxide and ethanol at room temperature. In vitro α-glucosidase inhibition and kinetic study of these compounds were performed. Furthermore, a docking study of the most potent compounds was also performed by Auto Dock Tools (version 1.5.6). RESULTS: Obtained results showed that all the synthesized compounds exhibited prominent inhibitory activities (IC50 = 85.0 ± 4.0-566.6 ± 8.6 µM) in comparison to acarbose as a standard inhibitor (IC50 = 750.0 ± 9.0 µM). Among them, the secondary amine derivative 4d with pendant indole group was the most potent inhibitor. Enzyme kinetic study of the compound 4d revealed that this compound competes with a substrate to connect to the active site of α-glucosidase and therefore is a competitive inhibitor. Moreover, a molecular docking study predicted that this compound interacted with the α-glucosidase active site pocket. CONCLUSION: Our results suggest that the coumarin-dithiocarbamate scaffold can be a promising lead structure for designing potent α-glucosidase inhibitors for the treatment of type 2 diabetes.

N-Cyclohexylimidazo[1,2-a]pyridine derivatives as multi-target-directed ligands for treatment of Alzheimer's disease.

Alzheimer's disease (AD) is the most common form of dementia. While drugs that target several pathways underlying AD have been proposed, effective treatments remain to be discovered. BACE1, an enzyme associated with AD progression, is a promising target for developing anti-Alzheimer drugs. To find novel multifunctional anti-Alzheimer agents, we designed and synthesized a series of new substituted benzyl-1H-1,2,3-triazol-4-yl-N-cyclohexylimidazo[1,2-a]pyridin-3-amine. The in vitro screening results revealed that most of the compounds exhibited moderate to potent BACE1 and BuChE inhibitory and antioxidant activities. Compounds 7f and 7g, bearing dichloro (2,3-Cl2 and 3,4-Cl2) moieties on the benzyl pendant were selected as the most active compounds in our BACE1 inhibitory assay with respective IC50 values of about 12 and 8.9 µM. In addition, compounds 7g and 7h (4-bromo derivative) showed the highest BuChE inhibitory activity with IC50 of 3.2 and 2.5 µM, respectively. Compound 7g also possessed antioxidant activity with an IC50 value of 10.2 µM and metal chelation potential. Moreover, docking studies were performed to investigate the possible mechanism of inhibition. Taken together, we demonstrate that N-cyclohexylimidazo[1,2-a]pyridine containing triazole motif derivatives deserve further investigation for anti-Alzheimer drug development.

New benzyl pyridinium derivatives bearing 2,4-dioxochroman moiety as potent agents for treatment of Alzheimer's disease: Design, synthesis, biological evaluation, and docking study.

A new series of benzyl pyridinium-2,4-dioxochroman derivatives 7a-o was synthesized and evaluated as new anti-Alzheimer agents. Among the synthesized compounds, the compounds 7f and 7i exhibited the most potent anti-AChE and anti-BuChE activities, respectively. The kinetic study of the compound 7f revealed that this compound inhibited AChE in a mixed-type inhibition mode. Furthermore, the docking study of the compounds 7f and 7i showed that these compounds bound to both the catalytic site (CS) and peripheral anionic site (PAS) of AChE and BuChE, respectively. The compound 7f also exhibited a greater self-induced Aß peptide aggregation inhibitory activity in compare to donepezil. Furthermore, the neuroprotective activity of this compound at 20 µM was comparable to that of the standard neuroprotective agent (quercetin).

Design, Synthesis, In vitro Cytotoxic Activity Evaluation, and Study of Apoptosis Inducing Effect of New Styrylimidazo[1,2-a]Pyridines as Potent Anti-Breast Cancer Agents.

BACKGROUND: This paper reports synthesis, cytotoxic activity, and apoptosis inducing effect of a novel series of styrylimidazo[1,2-a]pyridine derivatives. OBJECTIVE: In this study, anti-cancer activity of novel styrylimidazo[1,2-a]pyridines was evaluated. METHODS: Styrylimidazo[1,2-a]pyridine derivatives 4a-o were synthesized through a one-pot three-component reaction of 2-aminopyridines, cinnamaldehydes, and isocyanides in high yield. All synthesized compounds 4a-o were evaluated against breast cancer cell lines including MDA-MB-231, MCF-7, and T-47D using MTT assay. Apoptosis was evaluated by acridine orange/ethidium bromide staining, cell cycle analysis, and TUNEL assay as the mechanism of cell death. RESULTS: Most of the synthesized compounds exhibited more potent cytotoxicity than standard drug, etoposide. Induction of apoptosis by the most cytotoxic compounds 4f, 4g, 4j, 4n, and 4m was confirmed through mentioned methods. CONCLUSION: In conclusion, these results confirmed the potency of styrylimidazo[1,2-a]pyridines for further drug discovery developments in the field of anti-cancer agents.

Discovery of imidazopyridines containing isoindoline-1,3-dione framework as a new class of BACE1 inhibitors: Design, synthesis and SAR analysis.

Alzheimer's disease is characterized by chronic neurodegeneration leading to dementia. The main cause of neurodegeneration is considered to be the accumulation of amyloid-ß. Inhibiting BACE1 is a well-studied approach to lower the burden of amyloid-ß aggregates. We designed a series of imidazopyridines-based compounds bearing phthalimide moieties as inhibitors of BACE1. The compounds 8a-o were synthesized by the Groebke-Blackburn-Bienaymé three-component reaction of heteroaromatic amidines, aldehydes and isocyanides. Evaluating the BACE1 inhibitory effects of the synthesized compounds revealed that introducing an aminocyclohexyl moiety in the imidazopyridine core resulted in a significant improvement in its BACE1 inhibitory potential. In this regard, compound 8e was the most potent against BACE1 with an IC50 value of 2.84 (±0.95) µM. Molecular docking revealed that the nitrogen atom of imidazopyridines and the oxygen atom of the phenoxypropyl linker were involved in hydrogen bound interactions with Asp228 and Asp32 of BACE1 active site, respectively. The phthalimide moiety oriented toward the flap pocket and interacted with phe108, lle110, Trp115, Ile118 through van der Waal's and hydrophobic interactions. These findings demonstrate that imidazopyridines-based compounds bearing phthalimide moiety have the potential to decrease amyloid-ß levels and ameliorate the symptoms of Alzheimer's disease.

Novel domino procedures for the synthesis of chromene derivatives and their isomerization.

Novel tricyclic keto diesters have been synthesized by a one-pot three-component procedure via DABCO-catalyzed domino Knoevenagel-Michael addition reactions. Also, an efficient four-component reaction for the synthesis of another new group of tricyclic keto diesters has been developed via domino Knoevenagel-intramolecular oxo-Diels-Alder reactions. A selective thermal isomerization of the synthesized chromenes to fumarates is also described. X-ray analyses confirm unambiguously the structures of the products.

Novel approaches for the synthesis of a library of fluorescent chromenopyrimidine derivatives.

A library of some new fluorescent chromenopyrimidine derivatives has been synthesized by new approaches. Water-promoted and one-pot reaction can produce new dialkylylamino)-5H-chromeno[2,3-d]pyrimidin-2-yl) phenols. These compounds can also be produced using domino reaction. Two parallel methods are compared. Novel N-alkyl-N-phenyl-5H-chromeno[2,3-d]-pyrimidin-4-amines and 4-alkoxy-5H-chromeno[2, 3-d]pyrimidines are synthesized by Lewis-acid catalyzed reactions. The fluorescence emission intensity of the four compounds from each of libraries after excitation in 290 nm is measured. Compound 2-(4,5-bis(N-methyl-N-phenylamino)-5H-chromeno[2,3-d]pyrimidin-2-yl)phenol was isolated as a byproduct. The details of an interesting exchangeable intramolecular H- bonding of two of the new compounds are reported by X-ray analysis data.

2-Amino-4-(nitroalkyl)-4H-chromene-3-carbonitriles as New Cytotoxic Agents.

A series of 2-amino-4-(nitroalkyl)-4H-chromene-3-carbonitriles were synthesized by an efficient multicomponent reaction in aqueous media using DBU as a catalyst at room temperature. Mild condition, environment friendly procedure and excellent yields are the main advantages of this procedure. The cytotoxic activity of target compounds were evaluated against three cancer cell lines MDA-MB-231, MCF-7 and T47D in comparison with etoposide as reference drug. Generally, all compounds showed good cell growth inhibitory activity with IC(50) values less than 30 µg/mL. Their activities were comparable or more potent than standard drug etoposide. The 6-bromo- derivatives 7e and 7f showed promising cytotoxic activity with IC50 values in the range of 3.46-18.76 µg/mL, being more potent than etoposide against all tested cell lines.

(E)-3-Hy-droxy-5,5-dimethyl-2-(3-phenyl-prop-2-en-1-yl)cyclo-hex-2-en-1-one.

Five of the atoms of the six-membered cyclo-hexene ring of the title compound, C(17)H(20)O(2), are essentially coplanar (r.m.s. deviation = 0.006 Å), with the sixth (the dimethyl-methyl C atom) deviating from the mean plane of the five atoms by 0.610 (2) Å. This plane is nearly perpendicular to the cinnamyl portion, the two planes being aligned at 85.1 (1)°. Two mol-ecules are linked by an O-H⋯O hydrogen bond about a center of inversion. The cyclo-hexene ring is disordered over two directly overlapping positions. As a result, the hy-droxy group and the keto O atom cannot be distinguished from one another.

(E)-2-Bromo-benzaldehyde oxime.

The configuration of the C=N double bond of the title compound, C(7)H(6)BrNO, is E; the non-H atoms are approximately coplanar (r.m.s. deviation = 0.038 Å). In the crystal, pairs of mol-ecules are linked by a pair of O-H⋯N hydrogen bonds about a center of inversion, generating hydrogen-bonded dimers.

(5E)-Dimethyl 2-bromo-methyl-5-cyclo-hexyl-imino-2-phenyl-2,5-dihydro-furan-3,4-dicarboxyl-ate.

The mol-ecule of the title compound, C(21)H(24)BrNO(5), has a planar furan ring [maximum deviation = 0.025 (3) Å]. The carboxy-methyl group in the 3-position is nearly coplanar with this ring [dihedral angle = 7.9 (1)°], whereas that in the 4-position is nearly perpendicular to it [dihedral angle = 78.9 (1) Å].

1-(2-Eth-oxy-2-methyl-2H-chromen-3-yl)ethanone.

The Csp(3) atom of the chromenyl fused-ring system in the title compound, C(14)H(16)O(3), deviates by 0.407 (2) Šfrom the plane of the other atoms (r.m.s. deviation = 0.041 Å). The eth-oxy substituent occupies a pseudo-axial position.

4-(5-Bromo-2-hydroxy-phen-yl)but-3-ene-2-one.

The molecule of the title compound, C(10)H(9)BrO(2), a doubly conjugated unsaturated ketone, is almost planar (r.m.s. deviation of the non-H atoms = 0.039 Å). In the crystal structure, two mol-ecules are linked across a centre of inversion to form a hydrogen-bonded dimer by way of two O-H⋯O links.

N-(1,3-Thia-zol-2-yl)benzamide.

The title compound, C(10)H(8)N(2)OS, features a nonplanar mol-ecule [dihedral angle between the two aromatic rings = 43.6 (1)°]. Two mol-ecules are linked by N-H⋯N hydrogen bonds about a centre of inversion, giving rise to a hydrogen-bonded dimer.