Heteroaryl-Fused Triazapentalenes: Synthesis and Aggregation-Induced Emission.

A pyridine-fused triazapentalene shows weak fluorescence in solution and is readily accessible via nitrene-mediated cyclization. In this study, a modified Cadogan reaction was used to synthesize . Palladium-catalyzed reactions have been used as post-functionalization methods.

Simple generation of cleavable labels for multiplexed imaging.

The most common methods for multiplexed immunohistochemistry rely on cyclic procedures, whereby cells or tissues are repeatedly stained, imaged, and regenerated. Here, we present a simple and inexpensive approach for amine-targeted labeling of antibodies using a linker that can be easily cleaved by a mild reducing agent. This method requires only inexpensive and readily-available reagents, and can be carried out without synthetic experience in a simple one-pot reaction.

Host-Guest Assemblies of Polyoxovanadate Clusters as Supramolecular Catalysts.

Supramolecular functional materials can be used to overcome some of the most challenging tasks in materials science, where the dynamic nature of supramolecular interactions can be leveraged to fine-tune the properties of the material for a given task. The Lindqvist hexavanadate family of polyoxometalates (POMs) have emerged as particularly interesting candidates to be used in supramolecular materials due to their redox and Lewis acid properties that enable their application in the fields of energy conversion/storage or catalysis. Despite their promising potential, hexavanadate clusters are underrepresented in the field of supramolecular materials, mainly due to the synthetic challenges related to their inherent reactivity.

Synthesis of 3-heteroaryl-pyrrolo[2,3-b]pyridines as potent inhibitors of AP-2-associated protein kinase 1 (AAK1) with antiviral activity.

Inhibition of AP-2-associated protein kinase 1 (AAK1) has been shown to be a promising avenue for the development of broad-spectrum antiviral agents. On a previously described AAK1 inhibitor based on a pyrrolo[2,3-b]pyridine scaffold, the concept of isosterism was applied, by replacing a carboxamide linker by various five-membered heterocycles. It led to the discovery of a novel series of AAK1 inhibitors with IC values in the low nM range, that also displayed antiviral activity against the dengue virus and Venezuelan equine encephalitis virus.

Multi-Stimuli-Responsive Biocompatible Magnetic Nanocarrier as Drug Delivery System to MCF-7 Breast Cancer Cells.

Introduction: The last strategy in targeted drug delivery systems is to deliver the anticancer drug to the tumor tissue to increase its therapeutic effect and minimize its undesirable side effects. In line with this goal in this research, the redox/pH-responsive disulfide magnetic nanocarriers based on PF127-NH2/L-cysteine-CM-β-CD-FA were synthesized and evaluated in a doxorubicin delivery system.

Methods: We effectively surrounded Fe3O4 nanoparticles with SiO2 using the sol-gel method, and then confidently coated them with oleic acid on Fe3O4@SiO2 nanoparticles.

Structure-Aided Computational Design of Triazole-Based Targeted Covalent Inhibitors of Cruzipain.

Cruzipain (CZP), the major cysteine protease present in , the ethiological agent of Chagas disease, has attracted particular attention as a therapeutic target for the development of targeted covalent inhibitors (TCI). The vast chemical space associated with the enormous molecular diversity feasible to explore by means of modern synthetic approaches allows the design of CZP inhibitors capable of exhibiting not only an efficient enzyme inhibition but also an adequate translation to anti- activity. In this work, a computer-aided design strategy was developed to combinatorially construct and screen large libraries of 1,4-disubstituted 1,2,3-triazole analogues, further identifying a selected set of candidates for advancement towards synthetic and biological activity evaluation stages.

Synthesis and evaluation of isothiazolo[4,5-]pyridines as cyclin G-associated kinase (GAK) inhibitors.

Isothiazolo[4,3-]pyridines have been extensively explored as inhibitors of cyclin G-associated kinase (GAK). In order to expand the structure-activity relationship study and to discover other chemotypes that act as GAK inhibitors, the closely related isothiazolo[4,5-]pyridine scaffold was explored. An easy and efficient synthetic procedure to access 3,5- and 3,6-dihalogenated isothiazolo[4,5-]pyridines as key building blocks was developed.

Benzo-Fused BOPAM Fluorophores: Synthesis, Post-functionalization, Photophysical Properties and Acid sensing Applications.

A novel category of asymmetric boron chromophores with the attachment of two BF moieties denoted as BOPAM has been successfully synthesized via a one-pot three-step reaction starting from N-phenylbenzothioamide. This synthetic route results in the production of [a] and [b]benzo-fused BOPAMs along with post-functionalization of the [a]benzo-fused BOPAMs. The photophysical properties of these compounds have been systematically investigated through steady-state absorption and fluorescence emission measurements in solvents at both ambient and cryogenic temperatures, as well as in the solid state.

Synthesis and Investigation of Biological Activity of New Betulonic Acid Derivatives Containing 1,2,3-Triazole Fragments.

The results of this study showed that the compounds synthesized by the authors have significant potential due to their antibacterial and cytotoxic properties. The apparent antibacterial activity demonstrated by the compounds suggests that they are active antimicrobial agents against common microbial pathogens that cause various socially significant infectious diseases. Compound showed pronounced antimicrobial activity against the Gram-positive test strain ATCC 6538, and compound demonstrated pronounced antimicrobial activity against the Gram-negative test strain ATCC 25922 (MIC = 6.

Chemical space exploration with Molpher: Generating and assessing a glucocorticoid receptor ligand library.

Computational exploration of chemical space is crucial in modern cheminformatics research for accelerating the discovery of new biologically active compounds. In this study, we present a detailed analysis of the chemical library of potential glucocorticoid receptor (GR) ligands generated by the molecular generator, Molpher. To generate the targeted GR library and construct the classification models, structures from the ChEMBL database as well as from the internal IMG library, which was experimentally screened for biological activity in the primary luciferase reporter cell assay, were utilized.

Exploring the influence of hydrogen bond donor groups on the microstructure and intermolecular interactions of amorphous solid dispersions containing diflunisal structural analogues.

Drug-polymer intermolecular interactions, and H-bonds specifically, play an important role in the stabilization process of a compound in an amorphous solid dispersion (ASD). However, it is still difficult to predict whether or not interactions will form and what the strength of those interactions would be, based on the structure of drug and polymer. Therefore, in this study, structural analogues of diflunisal (DIF) were synthesized and incorporated in ASDs with poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA) as a stabilizing polymer.

Palladium-Catalyzed Arylations towards 3,6-Diaryl-1,3a,6a-triazapentalenes and Evaluation of Their Fluorescence Properties.

Methyl 4-(1,3a,6a-triazapentalen-3-yl)benzoate () shows interesting properties as a small molecule fluorophore. In the search for post-functionalization methods, palladium-catalyzed arylation reactions were demonstrated. Direct CH arylation reactions of with various aryl halides resulted in 3,6-diaryltriazapentalenes , although mostly in poor yields.

Voltammetric Sensing of Chloride Based on a Redox-Active Complex: A Terpyridine-Co(II)-Dipyrromethene Functionalized Anion Receptor Deposited on a Gold Electrode.

A redox-active complex containing Co(II) connected to a terpyridine (TPY) and dipyrromethene functionalized anion receptor (DPM-AR) was created on a gold electrode surface. This host-guest supramolecular system based on a redox-active layer was used for voltammetric detection of chloride anions in aqueous solutions. The sensing mechanism was based on the changes in the redox activity of the complex observed upon binding of the anion to the receptor.

On the origin of cooperativity effects in the formation of self-assembled molecular networks at the liquid/solid interface.

In this work we investigate the behaviour of molecules at the nanoscale using scanning tunnelling microscopy in order to explore the origin of the cooperativity in the formation of self-assembled molecular networks (SAMNs) at the liquid/solid interface. By studying concentration dependence of alkoxylated dimethylbenzene, a molecular analogue to 5-alkoxylated isophthalic derivatives, but without hydrogen bonding moieties, we show that the cooperativity effect can be experimentally evaluated even for low-interacting systems and that the cooperativity in SAMN formation is its fundamental trait. We conclude that cooperativity must be a local effect and use the nearest-neighbor Ising model to reproduce the coverage concentration curves.

Charge Transfer-Promoted Excited State of a Heavy-Atom-Free Photosensitizer for Efficient Application of Mitochondria-Targeted Fluorescence Imaging and Hypoxia Photodynamic Therapy.

Conventional photosensitizers (PSs) used in photodynamic therapy (PDT) have shown preliminary success; however, they are often associated with several limitations including potential dark toxicity in healthy tissues, limited efficacy under acidic and hypoxic conditions, suboptimal fluorescence imaging capabilities, and nonspecific targeting during treatment. In response to these challenges, we developed a heavy-atom-free PS, denoted as , by incorporating ethyl carbazole into a thiophene-fused BODIPY core. A comprehensive investigation into the photophysical properties of was conducted through a synergistic approach involving experimental and computational investigations.

Synthesis of a 3,7-Disubstituted Isothiazolo[4,3-]pyridine as a Potential Inhibitor of Cyclin G-Associated Kinase.

Disubstituted isothiazolo[4,3-]pyridines are known inhibitors of cyclin G-associated kinase. Since 3-substituted-7-aryl-isothiazolo[4,3-]pyridines remain elusive, a strategy was established to prepare this chemotype, starting from 2,4-dichloro-3-nitropyridine. Selective C-4 arylation using ligand-free Suzuki-Miyaura coupling and palladium-catalyzed aminocarbonylation functioned as key steps in the synthesis.

Identification of novel human CC chemokine receptor 8 (CCR8) antagonists via the synthesis of naphthalene amide and sulfonamide isosteres.

The human CC chemokine receptor 8 (CCR8) has been extensively pursued as target for the treatment of various inflammatory disorders. More recently, the importance of CCR8 in the tumor microenvironment has been demonstrated, spurring the interest in CCR8 antagonism as therapeutic strategy in immuno-oncology. On a previously described naphthalene sulfonamide with CCR8 antagonistic properties, the concept of isosterism was applied, leading to the discovery of novel CCR8 antagonists with IC values in the nM range in both the CCL1 competition binding and CCR8 calcium mobilization assay.

A Highly Efficient Strategy for One-Pot and Pseudo-Six-Component Synthesis of Hexahydroquinolines.

In this study, a homogeneous acid-catalyzed reaction of a series of benzaldehydes, benzylamines, and Meldrum's acid was presented, allowing the novel one-pot and multicomponent synthesis of hexahydroquinolines with high stereoselectivity. The current strategy has advantages including high regioselectivity, good efficiency, reasonable diversity, utilization of an inexpensive and safe catalyst, and easy purification of products by simple recrystallization. The current reaction utilizes 2 equiv of Meldrum's acid, 3 equiv of benzaldehyde derivatives, and one equiv of amine derivatives to yield (4'S,5'S,7'S)-1'-benzyl-2,2-dimethyl-4',5',7'-triphenyl-3',4',7',8'-tetrahydro-1'-spiro[[1,3]dioxane-5,6'-quinoline]-2',4,6(5')-trione derivatives.

Discovery of a novel androgen receptor antagonist, MEL-6, with stereoselective activity and optimization of its metabolic stability.

A new chemical scaffold with antagonistic activity towards the androgen receptor (AR) was identified. The parent compound, (3-Methoxy-N-[1-methyl-2-(4-phenyl-1-piperazinyl)-2-(2-thienyl)ethyl]benzamide) referred to as MEL-6, binds in the ligand binding pocket of AR and induces an antagonistic conformation of the ligand binding domain, even in presence of the antagonist-to-agonist switch mutations W741C, T877A and F876L-T877A. MEL-6 has antiproliferative effects on several AR positive prostate cancer cell lines.

Cycloaddition reactions of heterocyclic azides with 2-cyanoacetamidines as a new route to ,-diheteroarylcarbamidines.

A novel and efficient base-catalyzed, transition-metal-free method for the synthesis of diheterocyclic compounds connected by an amidine linker, including apart from the common 1,2,3-triazole ring, either an additional pyrimidinedione, 4-nitroimidazole, isoxazole, 1,3,4-triazole, 2-oxochromone or thiazole ring, has been developed. The process was facilitated by a strong base and includes the cycloaddition reaction of 3,3-diaminoacrylonitriles (2-cyanoacetamidines) to heterocyclic azides followed by a Cornforth-type rearrangement to the final products. The reaction is tolerant to various -monosubstituted 3,3-diaminoacrylonitriles and to different heterocyclic azides.

Covalent immobilization of N-heterocyclic carbenes on pristine carbon substrates: from nanoscale characterization to bulk catalysis.

To control the synthesis of designer catalysts on graphitic materials up to the nanometer scale, methods should be provided that combine both nanoscale characterization and bulk scale experiments. This work reports the grafting of N-heterocyclic carbene (NHC)-type catalysts on graphite, both at nanometer and bulk scale, as it allows increased insights into the nature of the immobilized catalysts.

Exploration of 1,2,3-triazolo fused triterpenoids as inhibitors of human coronavirus 229E targeting the viral nsp15 protein.

The coronavirus disease-19 (COVID-19) pandemic has raised major interest in innovative drug concepts to suppress human coronavirus (HCoV) infections. We previously reported on a class of 1,2,3-triazolo fused betulonic acid derivatives causing strong inhibition of HCoV-229E replication via the viral nsp15 protein, which is proposedly related to compound binding at an intermonomer interface in hexameric nsp15. In the present study, we further explored the structure-activity relationship (SAR), by varying the substituent at the 1,2,3-triazolo ring as well as the triterpenoid skeleton.