Effects of Terahertz Radiation on the Aggregation of Alzheimer's Aß42 Peptide.

The pathophysiology of Alzheimer's disease is thought to be directly linked to the abnormal aggregation of ß-amyloid (Aß) in the nervous system as a common neurodegenerative disease. Consequently, researchers in many areas are actively looking for factors that affect Aß aggregation. Numerous investigations have demonstrated that, in addition to chemical induction of Aß aggregation, electromagnetic radiation may also affect Aß aggregation. Terahertz waves are an emerging form of non-ionizing radiation that has the potential to affect the secondary bonding networks of biological systems, which in turn could affect the course of biochemical reactions by altering the conformation of biological macromolecules. As the primary radiation target in this investigation, the in vitro modeled Aß42 aggregation system was examined using fluorescence spectrophotometry, supplemented by cellular simulations and transmission electron microscopy, to see how it responded to 3.1 THz radiation in various aggregation phases. The results demonstrated that in the nucleation aggregation stage, 3.1 THz electromagnetic waves promote Aß42 monomer aggregation and that this promoting effect gradually diminishes with the exacerbation of the degree of aggregation. However, by the stage of oligomer aggregation into the original fiber, 3.1 THz electromagnetic waves exhibited an inhibitory effect. This leads us to the conclusion that terahertz radiation has an impact on the stability of the Aß42 secondary structure, which in turn affects how Aß42 molecules are recognized during the aggregation process and causes a seemingly aberrant biochemical response. Molecular dynamics simulation was employed to support the theory based on the aforementioned experimental observations and inferences.

Peptidyl Virus-Like Nanovesicles as Reconfigurable "Trojan Horse" for Targeted siRNA Delivery and Synergistic Inhibition of Cancer Cells.

The self-assembly of peptidyl virus-like nanovesicles (pVLNs) composed of highly ordered peptide bilayer membranes that encapsulate the small interfering RNA (siRNA) is reported. The targeting and enzyme-responsive sequences on the bilayer's surface allow the pVLNs to enter cancer cells with high efficiency and control the release of genetic drugs in response to the subcellular environment. By transforming its structure in response to the highly expressed enzyme matrix metalloproteinase 7 (MMP-7) in cancer cells, it helps the siRNA escape from the lysosomes, resulting in a final silencing efficiency of 92%. Moreover, the pVLNs can serve as reconfigurable "Trojan horse" by transforming into membranes triggered by the MMP-7 and disrupting the cytoplasmic structure, thereby achieving synergistic anticancer effects and 96% cancer cell mortality with little damage to normal cells. The pVLNs benefit from their biocompatibility, targeting, and enzyme responsiveness, making them a promising platform for gene therapy and anticancer therapy.

Visible-Light-Mediated Oxidative Cyclization of 2-Aminobenzyl Alcohols and Secondary Alcohols Enabled by an Organic Photocatalyst.

This paper describes a visible-light-mediated oxidative cyclization of 2-aminobenzyl alcohols and secondary alcohols to produce quinolines at room temperature. This photocatalytic method employed anthraquinone as an organic small-molecule catalyst and DMSO as an oxidant. According to this present procedure, a series of quinolines were prepared in satisfactory yields.

Recent Advances in c-Jun N-Terminal Kinase (JNK) Inhibitors.

c-Jun N-Terminal Kinases (JNKs), members of the Mitogen-Activated Protein Kinase (MAPK) signaling pathway, play a key role in the pathogenesis of many diseases including cancer, inflammation, Parkinson's disease, Alzheimer's disease, cardiovascular disease, obesity, and diabetes. Therefore, JNKs represent new and excellent target by therapeutic agents. Many JNK inhibitors based on different molecular scaffolds have been discovered in the past decade. However, only a few of them have advanced to clinical trials. The major obstacle for the development of JNK inhibitors as therapeutic agents is the JNKisoform selectivity. In this review, we describe the recent development of JNK inhibitors, including ATP competitive and ATP non-competitive (allosteric) inhibitors, bidentatebinding inhibitors and dual inhibitors, the challenges, and the future direction of JNK inhibitors as potential therapeutic agents.

Design, synthesis, and biological evaluation of 1-substituted -2-aryl imidazoles targeting tubulin polymerization as potential anticancer agents.

A series of novel 1-substituted-2-aryl imidazoles (SAI) were designed and synthesized based on our previously reported ABI (2-Aryl-4-Benzoyl Imidazole) analogs and on the structure of combretastatin A-4 (CA-4). These compounds showed potent antiproliferative activities against six human cancer cell lines with IC50 values in nano molar range. Among them, compound 3X exhibited the best anticancer activity with an average IC50 value of ∼100 nM. The compound maintains the mechanism of action by inhibiting tubulin polymerization, thus causing cell arrest at G2/M phase and apoptosis. In vivo efficacy studies indicated that 3X was highly effective in suppressing tumor growth in a MDA-MB-468 xenograft model of nude mouse with a TGI (Tumor Growth Suppression) of 77% at 60 mg/kg without causing significant toxicity. In addition, 3X displayed significantly better water solubility (36.70 µg/mL) than CA-4 (2.83 µg/mL). Molecular modeling study indicated that 3X binds well to the colchicine binding site in tubulin. Our results suggest that the novel SAI analogs deserve further investigation as potential anticancer agents.

N-Heterocyclic carbene copper catalyzed quinoline synthesis from 2-aminobenzyl alcohols and ketones using DMSO as an oxidant at room temperature.

A facile and practical process for the synthesis of quinolines through an N-heterocyclic carbene copper catalyzed indirect Friedländer reaction from 2-aminobenzyl alcohol and aryl ketones using DMSO as an oxidant at room temperature is reported. A series of quinolines were synthesized in acceptable yields.

Cyclometalated iridium(III)-guanidinium complexes as mitochondria-targeted anticancer agents.

Guanidinium-functionalized molecules are commonly studied for their use as pharmaceutically active compounds and drugs carriers. Herein, four cyclometalated iridium(III) complexes containing guanidinium ligands have been synthesized and characterized as potential anticancer agents. These complexes exhibit moderate antitumor activity in HeLa, MCF-7, HepG2, CNE-2, and A549 human tumor cells. Interestingly, all complexes showed higher cytotoxicity than cisplatin against a cisplatin-resistant cell line A549R, and less cytotoxicity on the nontumorigenic LO2 cells. Intracellular distribution studies suggest that these complexes are selectively localized in the mitochondria. Mechanism studies indicate that these complexes arrested the cell cycle in the G0/G1 phase and can influence mitochondrial integrity, inducing cancer cell death through reactive oxygen species (ROS)-dependent pathways.

Direct conversion of allyl arenes to aryl ethylketones via a TBHP-mediated palladium-catalyzed tandem isomerization-Wacker oxidation of terminal alkenes.

A TBHP-mediated palladium-catalyzed tandem isomerization-Wacker oxidation of terminal alkenes was developed. This methodology provides a new efficient and simple route for conversion of a range of allyl arenes directly into aryl ethylketones in good yields with high chemoselectivity.

Palladium-catalyzed Csp(2)-H carbonylation of aromatic oximes: selective access to benzo[d][1,2]oxazin-1-ones and 3-methyleneisoindolin-1-ones.

A highly selective palladium-catalyzed carbonylation of Csp(2)-H bonds with aromatic oximes for the synthesis of benzo[d][1,2]oxazin-1-ones and 3-methyleneisoindolin-1-ones has been developed. Interestingly, we found that the N-OH group of the oximes could be used as a directing group and/or an internal oxidant under different conditions. This transformation is supposed to proceed through a hydroxyl-directed ortho-Csp(2)-H carbonylation or activation of vinyl Csp(2)-H bond/ortho-Csp(2)-H carbonylation process. The uses of readily available starting materials, atmospheric pressure of carbon monoxide, as well as operational simplicity make this practical and atom-economical method particularly attractive.

A convenient regioselective synthesis of cyclopentadienones via palladium-catalyzed [2+2+1] cyclocarbonylation of alkynes.

A simple and efficient synthesis of cyclopentadienones via palladium-catalyzed cyclocarbonylation of alkynes under atmospheric pressure of carbon monoxide has been developed. The transformation was carried out under mild and ligand-free conditions, a wide range of substrates and exceptional functional group tolerance.

An efficient synthesis of 2,5-diimino-furans via Pd-catalyzed cyclization of bromoacrylamides and isocyanides.

A novel palladium-catalyzed cyclization of bromoacrylamides with isocyanides gives substituted 2,5-diimino-furans, which can be used as the precursor of maleamides. This synthesis likely proceeds, after isonitrile insertion into C­Pd(II) bond, through the coordination of the amide oxygen atom to the Pd(II) centre as a key step.

Palladium-catalyzed coupling of alkynes with unactivated alkenes in ionic liquids: a regio- and stereoselective synthesis of functionalized 1,6-dienes and their analogues.

A palladium-catalyzed regio- and stereoselective intermolecular tandem reaction of alkynes and unactivated 1,6-enols in ionic liquids is described, providing a practical, efficient, and versatile method for the synthesis of functionalized 1,6-dienes in moderate to good yields. The present reaction has high functional-group tolerance and gives products on a gram scale. Mechanistic studies indicate that the reaction might proceed via a chain-walking mechanism.

Metal-free synthesis of 2-aminobenzothiazoles via aerobic oxidative cyclization/dehydrogenation of cyclohexanones and thioureas.

A metal-free process for the synthesis of 2-aminobenzothiazoles from cyclohexanones and thioureas has been developed using catalytic iodine and molecular oxygen as the oxidant under mild conditions. Various 2-aminobenzothiazoles, 2-aminonaphtho[2,1-d]thiazoles, and 2-aminonaphtho[1,2-d]thiazoles were prepared via this method in satisfactory yields.

(Z)-5-Benzyl-idene-3-butyl-4-phenyl-1,3-oxazolidin-2-one.

In the title compound, C(20)H(21)NO(2), the benzyl group and the oxazolidin-2-one unit are each essentially planar, with maximum deviations of 0.026 (2) and 0.031 (2) Å, respectively. The dihedral angle between the phenyl ring and the oxazolidin-2-one unit is 69.25 (2)°. In the crystal, mol-ecules are linked by weak inter-molecular C-H⋯O and C-H⋯π inter-actions.