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Hybrid cis-stilbene Molecules: Novel Anticancer Agents.

The growing interest in anticancer hybrids in the last few years has resulted in a great number of reports on hybrid design, synthesis and bioevaluation. Many novel multi-target-directed drug candidates were synthesized, and their biological activities were evaluated. For the design of anticancer hybrid compounds, the molecules of stilbenes, aromatic quinones, and heterocycles (benzimidazole, imidazole, pyrimidine, pyridine, pyrazole, quinoline, quinazoline) were applied. A distinct group of hybrids comprises the molecules built with natural compounds: Resveratrol, curcumin, coumarin, and olea

Stereoselective synthesis of novel adamantane derivatives with high potency against rimantadine-resistant influenza A virus strains.

A series of (R)- and (S)-isomers of new adamantane-substituted heterocycles (1,3-oxazinan-2-one, piperidine-2,4-dione, piperidine-2-one and piperidine) with potent activity against rimantadine-resistant strains of influenza A virus were synthesized through the transformation of adamantyl-substituted N-Boc-homoallylamines 8 into piperidine-2,4-diones 11 through the cyclic bromourethanes 9 and key intermediate enol esters 10. Biological assays of the prepared compounds were performed on the rimantadine-resistant S31N mutated strains of influenza A - A/California/7/2009(H1N1)pdm09 and modern pand

Inactivation of tyrosinase photoinduced by pterin.

Tyrosinase catalyzes in mammals the first and rate-limiting step in the biosynthesis of the melanin, the main pigment of the skin. Pterins, heterocyclic compounds able to photoinduce oxidation of DNA and its components, accumulate in the skin of patients suffering from vitiligo, a chronic depigmentation disorder in which the protection against UV radiation fails due to the lack of melanin. Aqueous solutions of tyrosinase were exposed to UV-A irradiation (350 nm) in the presence of pterin, the parent compound of oxidized pterins, under different experimental conditions. The enzyme activity in t…

Efficient One-Pot Copper(I)-Catalyzed Azide-Alkyne Cycloaddition in Water: Triazole Synthesis, Catalytic Applications, DFT Studies, and Biological Evaluation.

A series of Cu-N-heterocyclic carbene (Cu-NHC) complexes (3a-e) was successfully synthesized and their structures verified by NMR, HRMS, and elemental analysis. These complexes displayed excellent catalytic performance in the 1,3-dipolar cycloaddition of alkynes with azides, producing 1,4-disubstituted triazoles (4a-e) in isolated yields of 80%-91%. The cycloaddition between phenylacetylene and various azides was also explored theoretically using DFT/B3LYP/6-311+G(d) methods. The cytotoxic properties of the obtained compounds were evaluated against A549, HCT116, and BEAS-2B cell lines, with se

Innovative approaches to the synthesis of five-membered heteroaromatics with emerging synthetic methodologies.

According to statistics, more than 70% of drugs that are available on the market contain heterocyclic units. Among them, five-membered heteroaromatics bearing nitrogen, oxygen, and sulfur have served as the most important structural motifs found in diverse pharmaceuticals. Emerging toolboxes, such as photocatalysis, biocatalysis, electrocatalysis and skeletal editing have showcased unprecedented avenues to access them. In fact, >300 publications on the topic of synthesis of five-membered heteroaromatics by using emerging toolboxes have been recorded in the last ten years, clearly indicating th

Molecular Editing of Ketones through N-Heterocyclic Carbene and Photo Dual Catalysis.

The molecular editing of ketones represents an appealing strategy due to its ability to maximize the structural diversity of ketone compounds in a straightforward manner. However, developing efficient methods for the arbitrary modification of ketonic molecules, particularly those integrated within complex skeletons, remains a significant challenge. Herein, we present a unique strategy for ketone recasting that involves radical acylation of pre-functionalized ketones facilitated by N-heterocyclic carbene and photo dual catalysis. This protocol features excellent substrate tolerance and can be a

Recent progress in metal assisted multicomponent reactions in organic synthesis.

To prepare complicated organic molecules, straightforward, sustainable, and clean methodologies are urgently required. Thus, researchers are attempting to develop imaginative approaches. Metal-catalyzed multicomponent reactions (MCRs) offer optimal molecular diversity, high atomic efficiency, and energy savings in a single reaction step. These versatile protocols are often used to synthesize numerous natural compounds, heterocyclic molecules, and medications. Thus far, the majority of metal-catalyzed MCRs under investigation are based on metal catalysts such as copper and palladium; however, c

NHC-Catalyzed Aza-Benzoin Condensation of N,N'-Dipyridin-2-yl Aminals with Aldehydes.

α-Amino ketones are useful compounds because of their synthetic utility and bioactivities. After observing the ability of N,N'-dipyridin-2-yl aminals to form imines in situ, the synthesis of α-amino ketones using N,N'-dipyridin-2-yl aminals was proposed. Through the NHC-catalyzed aza-benzoin reaction between aromatic/aliphatic aldehydes and N,N'-dipyridin-2-yl aminals, α-amino ketones, including aromatic, heterocyclic, and aliphatic versions, were synthesized with yields up to 99%. A direct route toward N-Boc-protected α-amino ketones from N,N,N'-tris-Boc aminals was also discovered, yielding

Near-Infrared Illumination of Native Tissues for Image-Guided Surgery.

Our initial efforts to prepare tissue-specific near-infrared (NIR) fluorescent compounds generated successful correlation between physicochemical properties and global uptake in major organs after systemic circulation and biodistribution. Herein, we focus on the effects on biodistribution based on modulating electronic influencing moieties from donating to withdrawing moieties at both the heterocyclic site and through meso-substitution of pentamethine cyanine fluorophores. These selected modifications harnessed innate biodistribution pathways through the structure-inherent targeting, resulting

Pushing the limits of the heat of detonation via the construction of polynitro bipyrazole.

The trinitromethyl group is a highly oxidized group that is found as an active functionality in many high-energy-density materials. The most frequently used previous synthetic method for the introduction of the trinitromethyl group is the nitration of heterocyclic compounds containing an acetonyl/ethyl acetate/chloroxime group. Now a novel strategy for constructing a trinitromethyl group (5) via nitration of an ethylene bridged compound, dipyrazolo[1,5-a:5',1'-c]pyrazine (2), is reported. In addition, the other two nitrated products (3 and 4) were obtained under different nitrating conditions.…

Synthesis and carbonic anhydrase activating properties of a series of 2-amino-imidazolines structurally related to clonidine1.

The Carbonic Anhydrase (CA, EC 4.2.1.1) activating properties of histamine have been known for a long time. This compound has been extensively modified but only in few instances the imidazole ring has been replaced with other heterocycles. It was envisaged that the imidazoline ring could be a bioisoster of the imidazole moiety. Indeed, we report that clonidine, a 2-aminoimidazoline derivative, was found able to activate several human CA isoforms (hCA I, IV, VA, VII, IX, XII and XIII), with potency in the micromolar range, while it was inactive on hCA II. A series of 2-aminoimidazoline, structu

Oxazolone-1,2,3-Triazole Hybrids: Design, Synthesis and Antimicrobial Evaluation.

BACKGROUND: Oxazolones and 1,2,3-triazoles are among the extensively studied heterocycles in medicinal chemistry. Both of these moieties are reported to possess a broad spectrum of biological activity including antimicrobial. OBJECTIVE: The objective of the current work is to design, synthesize and antimicrobial evaluation of some new oxazolone-1,2,3-triazole hybrids. METHODS: The designed oxazolone-1,2,3-triazole hybrids were synthesized using copper(I)-catalyzed azide-alkyne cycloaddition. The antimicrobial evaluation was carried out using serial dilution method. RESULTS: Most of the synt

Synthesis, antimicrobial and anti-inflammatory activities of some 1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles and 1,2,4-triazolo[3,4-b][1,3,4]thiadiazines bearing trichlorophenyl moiety.

The reaction of 2,3,5-trichlorobenzoic acid hydrazide with carbon disulfide and potassium hydroxide followed by treatment with hydrazine hydrate afforded 3-(2,3,5-trichlorophenyl)-4-amino-1,2,4-triazole-5-thione (6). Alternatively, this triazole was also synthesized by fusing 2,3,5-trichlorobenzoic acid with thiocarbohydrazide. Condensation of (6) with various aromatic carboxylic acids in the presence of phosphorous oxychloride or with phenacyl bromides afforded two series of fused heterocycles namely 6-(substituted aryl)-3-(2,3,5-trichlorophenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadizoles (7) a

Selective oxymetalation of terminal alkynes via 6-endo cyclization: mechanistic investigation and application to the efficient synthesis of 4-substituted isocoumarins.

The cyclization of heteroatom-containing alkynes with π acidic metal salts is an attractive method to prepare heterocycles because the starting materials are readily available and the organometallic compounds are useful synthetic intermediates. A new organometallic species in the heterocyclization provides an opportunity to synthesize heterocycles that are difficult to obtain. Herein, we describe a novel cyclic oxymetalation of 2-alkynylbenzoate with indium or gallium salts that proceeds with an unusual regioselectivity to give isocoumarins bearing a carbon-metal bond at the 4-position. This n

1,3-Dithiolane as a Privileged Scaffold in Bioactive Derivatives: Chiral Resolution and Assignment of Absolute Configuration.

The 1,3-dithiolane ring has been recently rehabilitated as a chemical scaffold in drug design. However, for derivatives that are substituted in position 4, the introduction of a chiral center on the heterocycle demands the separation and characterization of the stereoisomers. We report the first chiral resolution and absolute configuration (AC) assignment for (1,4-dithiaspiro[4.5]decan-2-yl)methanol (R/S)-1, a key synthon for dithiolane-based biologically active compounds. Using (semi)preparative enantioselective HPLC, we isolated enantiomeric 1. The AC was assigned by using (+)-1 for the enan

Leuverdazyls как Novel Potent Inhibitors of Enterovirus Reference.

Интровирусы (ЭМ) являются важными патогенами, вызывающими болезни человека с различными клиническими проявлениями. На сегодняшний день лечение интоевиральных инфекций в основном поддерживается, поскольку для их профилактики или лечения не принимаются никакие вакцины или противовирусные препараты. Здесь мы описываем антивирусные свойства и механизмы действий лейвавердазил-новельных гетероцикличных соединений с антиоксидантным потенциалом. Свинцовое соединение, 1а, продемонстрировало низкую цитотоксичность наряду с высокой активностью антиоксидантов и вирусов. Был выбран вирусный штамм, резистен

Совпадение в аннотации оригинала
Enteroviruses (EV) are important pathogens causing human disease with various clinical manifestations. To date, treatment of enteroviral inf … atment. Here, we describe the antiviral properties and mechanisms of action of leucoverdazyls-novel heterocyclic compounds with antioxidant potential. The lead compound, 1a, demonstrated low cytotoxicity along with high antioxidant and virus-inhibiting activity. A viral strain resistant to 1a was selected, and the development of resistance was shown to be accompanied by …

Cytotoxic Activity of Piperazin-2-One-Based Structures: Cyclic Imines, Lactams, Aminophosphonates, and Their Derivatives.

N-Heterocycles are considered as desirable scaffolds for the development of novel lead compounds for anticancer drug research. Among them, phosphorus-containing amino-derivatives play a crucial role. A series of imines and products of their further reactions with P-nucleophiles were obtained starting from vicinal bisamines. Reaction of ethylenediamine and α-carbonyl esters yielded in novel unexpected products, which structures were confirmed by crystallographic measurements. The cytotoxic activity evaluation was done on a variety of cell lines including HUH7, AKH12, DAOY, UW228-2, D283, D425,

[(1,2,5,6-η)-Cyclo-octa-1,5-diene](1-ethyl-3-isopropyl-1,3-imidazol-2-yl-idene)(tri-phenyl-phosphane)rhodium(I) tetra-fluorido-borate.

A new N-heterocyclic cationic rhodium(I) complex with a tetra-fluorido-borate counter-anion, [Rh(C8H14N2)(C8H12)(C18H15P)]BF4, has been prepared and structurally characterized. The cationic complex exhibits a distorted square-planar environment around the rhodium(I) ion. Two connections are made from rhodium(I) to the carbon atom of an N-heterocylic carbene ligand and to the phospho-rus atom of a tri-phenyl-phosphane ligand. The remaining two coordination sites are made via a bidentate inter-action from the two olefinic bonds of cyclo-octa-diene to the rhodium(I) ion. The compound includes an

Synthesis and Evaluation of Antibacterial and Antifungal Activities In vitro and In silico of Novel Morpholinoalkoxychalcones.

INTRODUCTION: Chalcone compounds exhibit diverse bioactivities, attracting significant interest. Morpholine is a heterocycle commonly used in medicinal chemistry. It could enhance the potency, pharmacokinetics, and bioactivities of its compounds. METHODS: Adding morpholine into the chalcone scaffold could help create new compounds with favorable bioactivities. In this study, a new parallel synthesis procedure has been developed. Using this procedure, 18 novel morpholinoalkoxychalcones have been successfully synthesized. They had chains with morpholine appended on ring A or ring B. All the syn

MIB guides: [89Zr]Zr-DFO-trastuzumab and [64Cu]Cu-NOTA-Trastuzumab for Preclinical Cancer Imaging.

Radiopharmaceuticals based on antibody biomolecules are widely used in oncology for positron emission tomography (PET). Trastuzumab, an antibody that targets the epidermal growth factor receptor 2 (HER2), has been extensively studied for both preclinical and clinical cancer imaging. This MIB guide specifically focuses on the radiolabeling of the antibody trastuzumab with zirconium-89 (89Zr) and copper-64 (64Cu) for PET imaging. The guide describes the steps for conjugating trastuzumab with p-SCN-Bn-deferoxamine (DFO) or 2,2',2''-(1,4,7-triazacyclononane-1,4,7-triyl)triacetic acid (p-SCN-Bn-NOT