Synthesis and evaluation of lipoic acid - donepezil hybrids for Alzheimer's disease using a straightforward strategy.

Alzheimer's disease is associated with a progressive loss of neurons and synaptic connections in the cholinergic system. Oxidative stress contributes to neuronal damages and to the development of amyloid plaques and neurofibrillary tangles. Therefore, antioxidants have been widely studied to mitigate the progression of Alzheimer's disease, and among these, lipoic acid has demonstrated a neuroprotective effect.

A Kinetic Approach to Synergize Bactericidal Efficacy and Biocompatibility in Silver-Based Sol-Gel Coatings.

Silver ions are antimicrobial agents with powerful action against bacteria. Applications in surface treatments, as Ag-functionalized sol-gel coatings, are expected in the biomedical field to prevent contaminations and infections. The potential cytotoxicity of Ag cations toward human cells is well known though.

Package-Less Liquid Phase Sensing Using Surface Acoustic Waves on Lithium Tantalate Oxide.

Surface acoustic wave (SAW) transducers propagating shear waves are compatible with sensing chemical compounds in a liquid phase. However, if the liquid surrounding the sensor possesses a higher permittivity than the piezoelectric substrate, then the interdigitated electrodes for converting the incoming electromagnetic wave to acoustic waves are susceptible to capacitive short-circuiting, leading to excessive insertion losses. By using high-permittivity lithium tantalate oxide (LTO), we demonstrate chemical sensing in water without the need for dedicated microfluidic packaging.

Toward conformational identification of molecules in 2D and 3D self-assemblies on surfaces.

The design of supramolecular networks based on organic molecules deposited on surfaces, is highly attractive for various applications. One of the remaining challenges is the expansion of monolayers to well-ordered multilayers in order to enhance the functionality and complexity of self-assemblies. In this study, we present an assessment of molecular conformation from 2D to 3D supramolecular networks adsorbed onto a HOPG surface under ambient conditions utilizing a combination of scanning probe microscopies and atomic force microscopy- infrared (AFM-IR).

Donepezil + chromone + melatonin hybrids as promising agents for Alzheimer's disease therapy.

We describe herein the design, multicomponent synthesis and biological studies of new donepezil + chromone + melatonin hybrids as potential agents for Alzheimer's disease (AD) therapy. We have identified compound 14n as promising multitarget small molecule showing strong BuChE inhibition (IC = 11.90 ± 0.

Synthesis, antioxidant and Aβ anti-aggregation properties of new ferulic, caffeic and lipoic acid derivatives obtained by the Ugi four-component reaction.

We report herein the synthesis antioxidant and Aβ anti-aggregation capacity of (E)-N-benzyl-N-[2-(benzylamino)-2-oxoethyl]-3-(aryl)acrylamides and related (R)-N-benzyl-N-(2-(benzylamino)-2-oxoethyl)-5-(1,2-dithiolan-3-yl)pentanamides 1-12. These compounds have been obtained, via Ugi four-component reaction, from modest to good yields. Their antioxidant analysis, using the DPPH and ORAC assays, allowed us to identify compounds 8 and 9, as potent antioxidant agents, showing also strong Aβ self-aggregation inhibition, two biological properties of interest in pathologies linked to the oxidative stress, such as Alzheimer's disease.

Tetrahydropyranodiquinolin-8-amines as new, non hepatotoxic, antioxidant, and acetylcholinesterase inhibitors for Alzheimer's disease therapy.

Herein we report an efficient two step synthesis and biological assessment of 12 racemic tetrahydropyranodiquinolin-8-amines derivatives as antioxidant, cholinesterase inhibitors and non-hepatotoxic agents. Based on the results of the primary screening, we identified 7-(3-methoxyphenyl)-9,10,11,12-tetrahydro-7H-pyrano[2,3-b:5,6-h']diquinolin-8-amine (2h) as a particularly interesting non-hepatotoxic compound that shows moderate antioxidant activity (1.83 equiv Trolox in the ORAC assay), a non competitive inhibition of hAChE (IC = 0.

Synthesis and Biological Assessment of Racemic Benzochromenopyrimidinimines as Antioxidant, Cholinesterase, and Aβ1-42 Aggregation Inhibitors for Alzheimer's Disease Therapy.

Given the complex nature of Alzheimer's disease (AD), compounds that are able to simultaneously address two or more AD-associated targets show greater promise for development into drugs for AD therapy. Herein we report an efficient two-step synthesis and biological evaluation of new racemic benzochromene derivatives as antioxidants, inhibitors of cholinesterase and β-amyloid (Aβ1-42 ) aggregation. Based on the results of the primary screening, we identified 15-(3-methoxyphenyl)-9,11,12,15-tetrahydro-10H,14H-benzo[5,6]chromeno[2,3-d]pyrido[1,2-a]pyrimidin-14-imine (3 e) and 16-(3-methoxyphenyl)-9,10,11,12,13,16-hexahydro-15H-benzo[5',6']chromeno[2',3':4,5]pyrimido[1,2-a]azepin-15-imine (3 f) as new potential multitarget-directed ligands for AD therapy.

Novel aminotetrazole derivatives as selective STAT3 non-peptide inhibitors.

The development of inhibitors blocking STAT3 transcriptional activity is a promising therapeutic approach against cancer and inflammatory diseases. In this context, the selectivity of inhibitors against the STAT1 transcription factor is crucial as STAT3 and STAT1 play opposite roles in the apoptosis of tumor cells and polarization of the immune response. A structure-based virtual screening followed by a luciferase-containing promoter assay on STAT3 and STAT1 signaling were used to identify a selective STAT3 inhibitor.

Donepezil-ferulic acid hybrids as anti-Alzheimer drugs.

Background: Due to the complex nature of Alzheimer's disease, there is a renewed and growing search for multitarget drugs.

Results: Donepezil-ferulic acid hybrids (DFAHs) were prepared by the one-pot Ugi-4CR in low-to-moderate yields. DFAHs are potent antioxidant agents, showing oxygen radical absorbance capacity values in the range 4.

Novel tacrine-grafted Ugi adducts as multipotent anti-Alzheimer drugs: a synthetic renewal in tacrine-ferulic acid hybrids.

Herein we describe the design, multicomponent synthesis, and biological, molecular modeling and ADMET studies, as well as in vitro PAMPA-blood-brain barrier (BBB) analysis of new tacrine-ferulic acid hybrids (TFAHs). We identified (E)-3-(hydroxy-3-methoxyphenyl)-N-{8[(7-methoxy-1,2,3,4-tetrahydroacridin-9-yl)amino]octyl}-N-[2-(naphthalen-2-ylamino)2-oxoethyl]acrylamide (TFAH 10 n) as a particularly interesting multipotent compound that shows moderate and completely selective inhibition of human butyrylcholinesterase (IC50 =68.2 nM), strong antioxidant activity (4.

Quinolone-benzylpiperidine derivatives as novel acetylcholinesterase inhibitor and antioxidant hybrids for Alzheimer disease.

Design, synthesis and evaluation of new acetylcholinesterase inhibitors by combining quinolinecarboxamide to a benzylpiperidine moiety are described. Then, a series of hybrids have been developed by introducing radical scavengers. Molecular modeling was performed and structure activity relationships are discussed.

Self-assembly of a halogenated molecule on oxide-passivated Cu(110).

The supramolecular self-assembly of brominated molecules was investigated and compared on Cu(110) and Cu(110)-O(2×1) surfaces under ultrahigh vacuum. By using scanning tunnelling microscopy, we show that brominated molecules form a disordered structure on Cu(110), whereas a well-ordered supramolecular network is observed on the Cu(110)-O(2×1) surface. The different adsorption behaviors of these two surfaces are described in terms of weakened molecule-substrate interactions on Cu(110)-O(2×1) as opposed to bare Cu(110).

Noncovalent bicomponent self-assemblies on a silicon surface.

Two-dimensional supramolecular multicomponent networks on surfaces are of major interest for the building of highly ordered functional materials with nanometer-sized features especially designed for applications in nanoelectronics, energy storage, sensors, etc. If such molecular edifices have been previously built on noble metals or HOPG surfaces, we have successfully realized a 2D open supramolecular framework on a silicon adatom-based surface under ultrahigh vacuum with thermal stability up to 400 K by combining molecule-molecule and molecule-silicon substrate interactions. One of these robust open networks was further used to control both the growth and the periodicity of the first bicomponent arrays without forming any covalent bond with a silicon surface.

Dipole-driven self-organization of zwitterionic molecules on alkali halide surfaces.

We investigated the adsorption of 4-methoxy-4'-(3-sulfonatopropyl)stilbazolium (MSPS) on different ionic (001) crystal surfaces by means of noncontact atomic force microscopy. MSPS is a zwitterionic molecule with a strong electric dipole moment. When deposited onto the substrates at room temperature, MSPS diffuses to step edges and defect sites and forms disordered assemblies of molecules.

Reversible single molecular switch operating at 300 K on a surface.

A single 4-pyridylazobenzene molecule is observed at room temperature on a Si(111)-B surface by using scanning tunnel microscopy. The reversible conformational switching of this molecule is induced by tunneling electrons and observed at room temperature. This process is based on an intramolecular rotation of a single phenyl group without isomerization of the N=N double bond.