Triazole Fragment Research Articles

Lanthanide complexes of related click tripodal 1,2,3-triazole-containing ligands on the Ph<sub>3</sub>P(O) platform. The N<sup>2</sup> and N<sup>3</sup> coordination of triazole fragments

The coordination and extraction properties of two related tripodal ligands differed by types of addition of the triazole fragment and linker length in the {2-[(4-Ph-1,2,3-triazol-1-yl)CH2CH2O]C6H4}3P(O) (L1) and {2-[(1-Ph-1,2,3-triazol-4-yl)CH2O]C6H4}3P(O) (L2) are compared. The structures of the complexes [Lа(NO3)3L1] (I) and [Lu(NO3)3L1] (II) are studied in the solid phase (elemental analysis, IR and Raman spectroscopy) and in solutions (IR and multinuclear1H,13C, and31P NMR spectroscopy). A normal coordinate analysis at the TPSS-D4/Def2-SVP level is performed for an isolated molecule of the model complex [La{P(O),N3,N2-L3}(O,O-NO3)3] (L3= {2-[(4-Me-1,2,3-triazol-1-yl)CH2CH2O]C6H4}3-P(O)). According to the set of spectral and quantum chemical data, ligand L1exhibits the tridentate P(O),N2,N2coordination in lanthanide complexes I and II. These are neutral complexes in the solid state and in CD3CN solutions, and the dynamic equilibrium of the neutral and ionic complexes is observed in CDCl3. Unlike ligand L1, ligand L2exhibits the tetradentate P(O),N3,N3,N3coordination in the [Ln(NO3)3L2] complexes with the same metals (Ln = La3+, Lu3+) in solutions. The efficiency of extraction of microquantities offelements from the aqueous phase to 1,2-dichloroethane by compounds L1and L2is discussed in comparison with the structures of the complexes of both ligands in solutions.

PDMS-based copolymers with polyurea blocks and 1,2,3-triazole blocks obtained by CuAAC polymerization for 3D printing

Polydimethylsiloxanes with improved mechanical properties that can be processed by 3D printing are in high demand for scientific and practical applications. In our article, we proposed the synthesis of new PDMS copolymers with urethane and triazole fragments using the CuAAC reaction mechanism, as well as 3D printing with the obtained copolymers. Two types of copolymers, with molecular weights of 3000 and 6000 Da of PDMS block length, were prepared and characterized by GPC, IR spectroscopy, TGA, DSC, TMA, SAXS, and rheological measurements to determine their physicochemical properties. The synthesized copolymers were found to be suitable for processing by extrusion 3D printing. This demonstrated the ability to 3D print macroscale models of varying shapes and complexity. The resulting materials retained their printed shape over time.

Synthesis of triazole AD-1 derivatives and its mechanism of mediating DNA damage of ROS in lung cancer cells

Based on the significant biological activities and the remarkable physical and chemical properties of 1H-1,2,3-triazole pharmacophore, we herein adopted the strategy of click chemistry to combine the triazole fragment and the unique scaffold of 25-OCH3-PPD (AD-1) to design a series of potent compounds inducing apoptosis and DNA damage. The anti-proliferative effect was verified by MTT assay and colony formation assay. DNA double-stand breaks (DSBs) were obtained by observing the nuclear focus formation and the protein expression of γ-H2AX. Cell cycle arrest was evaluated by the cycle-related proteins such as CDK2, CDK4, CDK6, Cyclin D1 and P21. Apoptosis was assessed by flow cytometry, mitochondrial membrane potential (MMP) detection and the expression of apoptosis-related proteins. Reactive oxygen species (ROS) generation was measured with 2′, 7′-dichlorofluorescein diacetate (DCFH-DA) staining. According to SAR analysis, the most potent compound 6a exhibited great inhibitory effect against A549 cells, which IC50 value of 2.84 ± 0.68 μM. Furthermore, 6a remarkably induced DNA damage, cell cycle arrest and apoptosis in A549 cells. 6a treatment increased the levels of ROS. Network pharmacology and molecular docking predicted the potential signaling pathways and ligand-receptor interactions, and the results of western blotting showed that 6a inhibited the PI3K/Akt/Bcl-2 signaling pathway by decreasing PI3K and Bcl-2 and total level of Akt expression, while Bax and Cyt c were increasing in 6a-treated A549 cells. As mentioned above, 6a has a potent inhibitory effect in A549 cells through induction of DNA damage, apoptosis via ROS generation and modulation of PI3K/Akt/Bcl-2 signaling pathway.

Synthesis and Anti TB Screening of α-Acyloxy Carboxamides via Passerini MCRs Prompted by GaCl3 and PEG-400 Media

Aims: The Isocyanides based Multi-component reactions (IMCRs), and Passerini reactions were performed by using GaCl3 and PEG-400 media to generate a library of new scaffolds. Background: The Isocyanides Multi-component reactions (IMCRs) have proven their importance due to their major advantages in synthetic and medicinal areas. Among various IMCRs, Passerini stands for their pertinency in the novel adducts articulation and generates an amide functionality which shows unbeatable efficiency towards the generation of lead scaffolds. In the research fields, PEG is acting as a versatile greener solvent due to its beneficial economic advantages. In general, chiral-based separation is always a headache for the chemist and researchers tend to generate routes with major products such as single isomers. Most MCRs studied with metal-based synthesis and rather use Au or Pt-based catalyst, Gallium that has been widely explored in chiral Lewis acid catalysis, organo-catalysis, or cooperative catalysis to generate a library of compounds with high stereoselectivity with mild reaction conditions. Objective: To find diverse scaffolds in the field of organic chemistry using easily accessible metal catalysts. Methods: In this article, Enantiomerically pure, 2-(((1H-benzo[d][1,2,3]triazol-1-yl)methyl)amino)-2-oxo-1-substitutedphenylethyl pyrazine-2-carboxylate (4a-4j), produced through a three-component passerine coupling reaction under GaCl3 as a Lewis acid-promoted conditions with diastereose-letivity ranging from moderate to good. Results: The designed approach exhibited an in situ single-step-economical path to enantiomerically pure, α-acyloxy carboxamides with pyrazine and 1H-benzo[d][1,2,3]triazole fragments employing the greener way of media through “PEG-400”. In an anti-TB screening against H37Rv, the withdrawing groups showed excellent activity compared to the donating groups Conclusion: It was expected that the Lewis acid-PEG pairs could serve as the best catalytic transfor-mations in eco-friendly ways and enrich the pure enantiomer of the adduct. On the medicinal side, the isolated library of compounds was screened for their biological activity against “Mycobacterium Tubercu-losis H37Rv” and 4f featuring “4-F” as a substituent was found to be most active [MIC: 12.5 μg/mL].

Eugenol derivatives containing 1,2,3-triazole-chalcone hybrids for shikimate kinase inhibition

Eugenol, a primary component of clove oil, is a compound of considerable interest in medicinal chemistry due to its demonstrated potential as an effective agent in various therapeutic applications. In this study, a series of eugenol derivatives were designed and synthesized based on the hybridization of eugenol with 1,2,3-triazole and chalcone moieties. Compound 5j and 5k were denoted as lead structures against Mycobacterium tuberculosis Shikimate Kinase (MtSK). Moreover, the docking studies indicated that both the eugenol and triazole fragments in compound 5j and 5k played a pivotal role in the inhibition activity of MtSK, owing to their binding interactions with Arg58, Pro118, and Arg136 residues. Furthermore, in silico drug-likeness prediction analysis suggested that the majority of the synthesized compounds exhibit good oral bioavailability based on their molecular properties and Lipinski’s Rule of Five predictions.

Lanthanide Complexes of Related Click Tripodal 1,2,3-Triazole-Containing Ligands on the Ph3P(O) Platform. The N2 and N3 Coordination of Triazole Fragments

Lanthanide Complexes of Related Click Tripodal 1,2,3-Triazole-Containing Ligands on the Ph3P(O) Platform. The N2 and N3 Coordination of Triazole Fragments

Copper-Catalyzed Azide-Alkyne Cycloaddition-Oriented Multifunctional Bio-Orthogonal Linker BPPA: Design, Synthesis and Evaluation.

The multifunctional linker molecules are crucial for the bio-orthogonal reaction for proteomic target profiling. Herein, we wish to present a novel type of biotin-based tetra-functional bio-orthogonal linkers 3a-3h named BPPA which, possessing a unique photolabile phenacyl ester motif, were readily prepared in 85-90% yields by a simple and green one-step protocol from commercially available and inexpensive reagents of biotin acids and 4'-ethynyl/azido 2-bromoacetophenones. The typical click reaction of BPPA linkers 3a and 3e via copper-catalyzed azide-alkyne cycloaddition (CuAAC) took place easily, resulting in the corresponding BPPA-triazole adducts 4a and 4b in nearly quantitative yields. A further cleavability evaluation of 4a and 4b demonstrated that the expected C-O bond detachment could be accomplished efficiently and rapidly by UV irradiation or by ammonia hydrolysis, respectively, resulting in the residual (hydroxyl)acetylphenyl triazole fragment supposed to be attached to proteins during biological manipulations. The BPPA linkers, with dual clickable options of either the terminal azide or alkyne clickable group, exhibit high potentials for various CuAAC-oriented bio-orthogonal reactions.

Environmentally Friendly Synthesis and Self‐Catalytic Hydrolysis of Triazole‐Modified Organosilanes for Polysiloxane Production

AbstractOrganotrialkoxysilanes are unique compounds that play an important role in modern science and industry. Their structure determines their varied use both in production and academic research. The development of the synthesis of organotrialkoxysilanes and polymers based on them, taking into account environmental realities, is an important task. In our work, we present an original approach for the preparation of organotriethoxysilanes, starting from azidoalkyltriethoxysilanes and various types of substrates containing a terminal triple bond, by the azide‐alkyne cycloaddition (CuAAC) mechanism without the use of solvents, catalyst ligands, and amines. We also found the self‐catalyzing effect of the triazole fragment resulting from the azide‐alkyne cycloaddition in the reaction of hydrolysis and condensation of alkoxy groups, which made it possible to obtain a series of silsesquioxane products only by adding water, without the use of catalysts. As a result, a new, original scheme for the preparation of organosilicon organotrialkoxysilanes of a monomeric structure with their subsequent transformation into silsesquioxane polymers under “green” conditions is built.

An overview on 1,2,4-triazole and 1,3,4-thiadiazole derivatives as potential anesthesic and anti-inflammatory agents

The aim. The purpose of this review is to summarize data on the synthesis and structural modification of heterocyclic systems with triazole and thiadiazole fragments in molecules as promising objects in bioorganic and medicinal chemistry.
 Materials and methods. The research based on bibliosemantic and analytical methods using bibliographic and abstract databases, as well as databases of chemical compounds.
 Results. Modern medicinal chemistry faces many challenges, one of which is the determination of the activity and specificity of therapeutic agents. Recent scientific data showed that triazoles and/or thiadiazoles have broad spectrum of biological activities, in particular antimicrobial, antifungal, antiviral, anticancer and anticonvulsant. Synthetic research allows to propose a whole number of new molecular design directions of biological active triazole and/or thiadiazole derivatives, as well as to obtain directed library that include hundreds of new compounds. This review is an effort to summarize data of its analgesic and anti-inflammatory activity over the last decade. We summarized and analyzed the series of triazole and/or thiadiazole derivatives and provided data of their structure-activity relationship. For optimization and rational design of highly active molecules with optimal «drug-like» characteristics and discovering of possible mechanism of action SAR, QSAR analysis and molecular docking were summarized.
 Conclusions. It has been shown that heterocyclic systems containing fragments of triazole and / or thiadiazole are a significant source of promising analgesic and/or anti-inflammatory agents. It has been established that the mentioned heterocyclic derivatives have a high selectivity of action, low toxicity and an effect commensurate with standard drugs

Ditopic pyridyl-benzothiazole – Pyridylmethylene-2-thiohydantoin conjugates: Synthesis and study in complexation with CuCl2

New ditopic ligands (L) consisting of 2-(2-pyridyl)benzothiazole and 5-pyridylmethylene-2-thioimidazol-4-one moieties linked with polymethylene chains of various lengths (compounds 4) or triazole-containing linker (compounds 9, 11) were synthesized and their coordination properties in the reactions with CuCl2 were investigated. All the obtained copper complexes had the LCuCl2 composition. Ligands 4 with polymethylene linkers coordinate CuCl2 initially at the 5-pyridylmethylene-2-thioimidazolone moiety, but then copper chloride migrates to the 2-pyridylbenzothiazole fragment. In contrast, ligands 9, 11 with the triazole-containing linkers coordinate CuCl2 at 5-pyridylmethylene-2-thio-imidazolone and triazole fragments, and then the structure of the complex in the solution does not change. In DMF, the initially formed Cu2+ complexes may be reduced to Cu1+ compounds, based on electrochemical investigation data.

Photophysical and Electrical Properties of Highly Luminescent 2/6-Triazolyl-Substituted Push-Pull Purines.

New push–pull N(9)-alkylated 6-piperidino-2-triazolylpurine and 2-piperidino-6-triazolylpurine derivatives are synthesized, and their optical and optoelectronic properties are comprehensively characterized with experimental and computational methods. The compounds possess intense violet or blue fluorescence with fluorescence quantum yields of up to 91% in solution and 40% in host-free films. Depending on their structural composition, the compounds have ionization energy in the range of 5.25–6.04 eV, electron affinity of 2.18–3.15 eV, and triplet energy of 2.52–2.95 eV. Due to the presence of hole-transporting purine and electron-transporting triazole fragments, compounds exhibit bipolar charge-transportation ability. Despite the favorable emissive properties of the studied push–pull purines, their electroluminescence in thin films is quenched owing to large current densities that are present even at a moderate driving voltage. This marks application directions related to a predominantly charge-transportation functionality as the most suitable for this compound class.

DFT Quantum-Chemical Calculation of Thermodynamic Parameters and DSC Measurement of Thermostability of Novel Benzofuroxan Derivatives Containing Triazidoisobutyl Fragments.

New derivatives of benzofuroxan containing triazidoisobutyl fragments, opening the way for the creation of highly effective compositions with an increased value of energy characteristics, were synthesized for the first time. Such compounds are also an excellent platform for further modification and for the preparation of new biologically-active compounds containing tetrazole and triazole fragments. Calculations of heats of formation performed with the DFT (density functional theory) method showed that the studied compounds are high-energetic density ones, the enthalpies of formation of which are comparable to the enthalpies of formation of similar benzofuroxan derivatives and exceeds experimental enthalpy of formation of CL-14 (5,7-diamino-4,6-dinitrobenzofuroxan). The analysis of DSC indicates a sufficiently high thermal stability of the synthesized azidobenzofuroxans, which are acceptable for their use as components in the creation of highly efficient compositions with an increased value of energy characteristics.

Competing N vs. P(O),C(O)-coordination in complexes of mono- and bis-1,2,3-triazole ligands modified by carbamoylmethylphosphine oxide fragments with palladium(II), uranyl(II), and lanthanum(III): Solid and solution structures

Six new complexes [PdCl2(L1)2] (1), [PdCl2(L2)2]·2H2O (2), [PdCl2(L3)] (3), [UO2(L2)(NO3)2]·MeCN, (4), [(UO2)2(L3)(NO3)4] (5), [La(L2)2(NO3)3] (6) (L1 – 1-phenyl-4-propyl-1,2,3-triazole, L2, and L3 – mono- and bis-1,2,3-triazole ligands decorated with carbamoylmethylphosphine oxide (CMPO) fragments, respectively) were synthesized and characterized by elemental analysis and IR and Raman spectroscopy. The structures of complexes 1, 2, 4–6 have been determined by single-crystal X-ray crystallography. The ligands L2 and L3 display P(O),C(O) coordination mode with U(VI), and La(III), but N3 mode with Pd(II) in both solid state and solutions. Various intra- and intermolecular hydrogen bonding interactions involving nitrogen and hydrogen atoms of 1,2,3-triazole fragments were revealed in all studied crystalline complexes irrespective of whether triazole fragment coordinates to metal cation (1, 2) or not 4–6). The complex 1 displayed non-classical triazolyl CH…Cl– hydrogen bonding. These hydrogen bonds were also studied by QTAIM theory. Normal coordinate analysis of the vibrations at the DFT level was performed for the ligand L1 and its complex 1. Solution structure of all complexes has been investigated by IR and multinuclear (1H, 13C, and 31P) NMR spectroscopy. Extraction efficiency of Pd(II), U(VI), and La(III) from 3 M HNO3 into 1,2-dichloroethane using extractants L2 and L3 and the known CMPO extractant – Ph2P(O)CH2C(O)NBu2 is discussed in comparison with structure of the corresponding complexes in solutions.

α-naphthoflavone-derived cytochrome P450 (CYP)1B1 degraders specific for sensitizing CYP1B1-mediated drug resistance to prostate cancer DU145: Structure activity relationship

We previously discovered extrahepatic cytochrome P450 1B1 (CYP1B1) degraders able to overcome drug resistance toward docetaxel using a PROTACs technology, however, the underexplored structure activity relationships and poor water solubility posed a major hurdle in the development of CYP1B1 degraders. Herein, continuous efforts are made to develop more promising α-naphthoflavone (ANF)-derived chimeras for degrading CYP1B1. Guided by the strongest ANF-derived CYP1B1 degrader 3a we ever reported, 17 ANF analogues are designed and synthesized to evaluate the CYP1B1 degradation and resultant resistance reversal. In degrading CYP1B1 and sensitizing drug resistance, 4d with a 1, 5-cis triazole coupling mode at (C3′) of B ring of ANF exhibited the similar potency as 3a carrying a 1, 4-trans triazole fragment at (C4′) of B ring, but more obvious selectivity of 4d toward CYP1B1 over CYP1A2 is observed. When an oxygen was inserted into the linker of 4d, 4f demonstrated better water solubility, a more potent ability in degrading CYP1B1 and reversing drug resistance, and a promising selectivity. Collectively, a substitution position, an alkyne-azide cyclization and a liker type significantly affect the ability of ANF-thalidomide conjugates in eliminating drug resistance of CYP1B1-expressing DU145 (DU145/CY) cells to docetaxel via targeted CYP1B1 degradation.

Identification of a BAZ2A Bromodomain Hit Compound by Fragment Joining.

The bromodomains of BAZ2A and BAZ2B (bromodomain adjacent to zinc finger domain proteins 2) are among the most hard to drug of the 61 human bromodomains. While little is known about the role of BAZ2B, there is strong evidence for the opportunity of targeting BAZ2A in various cancers. Here, a benzimidazole–triazole fragment that binds to the BAZ2A acetyl lysine pocket was identified by a molecular docking campaign and validated by competitive binding assays and X-ray crystallography. Another ligand was observed in close proximity by soaking experiments using the BAZ2A bromodomain preincubated with the benzimidazole–triazole fragment. The crystal structure of BAZ2A with the two ligands was employed to design a few benzimidazole–triazole derivatives with increased affinity. We also present the engineering of a BAZ2A bromodomain mutant for consistent, high-resolution crystallographic studies.

Dyeing of polyester fibers with sulfur- and nitrogen-containing anthraquinone derivatives

A series of disperse dyes, 9,10-anthraquinone containing dithiocarbamate, thiourea and triazole fragments, were prepared via consecutive refunctionalization of aminoanthraquinones in our previous studies and their structures were confirmed by the 1H-, 13C-NMR, IR spectra, LC-MS and elemental analysis data. The obtained compounds were applied on polyester fabrics by the exhaustion method at 130?C at pH 4.0-5.0, and their dyeing properties were evaluated by color measurements, the washing fastness test and the light fastness test. Many of these dyes gave solid and level dyeings on polyester fabric with low % concentration of dye. The dyed samples displayed very good color fastnesses. The color change and staining test results were quite good with ratings of ?4-5? or above. The light fastness test results were also satisfactory for the most of the dyed samples.

New tripodal ligand on the triphenylphosphine oxide platform with 1,2,3-triazole side arms: synthesis, structure, coordination, and extraction properties

New hybrid tripodal propeller ligands on the triphenylphosphine oxide platform with triazole rings in the side arms and alkyl and aryl substituents in the triazole fragments have been synthesized by the click reaction. Composition and structure of the prepared compounds have been established by vibrational (IR, Raman) and multinuclear (1H, 13C, 31P) NMR spectroscopy, elemental analysis, and mass spectrometry. Coordination and extraction properties of the prepared compounds toward Pd(II) have been studied by the example of one of the ligands.

Synthesis, characterization and cytotoxic activity evaluation of 4-(1,2,3-triazol-1-yl) salicylic acid derivatives

A novel series of 4-(1,2,3-triazol-1-yl) salicylic acid derivatives was synthesized from 4-azidosalicylic acid and diverse alkynes using copper catalyzed azide-alkyne cycloaddition as key process and fully characterized by using different analytical techniques. The in vitro antiproliferative activity of these new compounds was explored against a series of tumoral cell lines which included U251 (human glioblastoma), PC-3 (human prostate cancer cell line), K562 (human leukemia), HCT-15 (human colorectal adenocarcinoma), MCF-7 (human breast adenocarcinoma) and SKLU (human lung adenocarcinoma), showing selective activity in some compounds. Moreover, molecular docking studies suggest a strong interaction between ARG-154 in STAT3 and the triazole fragment which can explain the inhibitory activity observed in these compounds.

New terpyridine derivatives of thiacalix[4]arenes in solution and at the water-air interface

New di- and tetrasubstituted thiacalix[4]arenes in cone and 1,3-alternate configurations containing terpyridine and triazole fragments at the lower rim of the macrocycle, as well as model triazole-terpyridine, are synthesized. The structures and purity of the compounds are confirmed by NMR spectroscopy and high-resolution MALDI mass spectrometry. The compounds form luminescent complexes with lanthanide cations (europium and terbium) in a chloroform-methanol (10: 1) system during fluorimetric titration. The possibility of antenna ef ect during fluorescence sensitization in lanthanides by the thiacalixarene ligands is demonstrated. Successful immobilization of the terpyridine receptors on a solid substrate makes it possible to consider the Langmuir-Blodgett films on the basis of these receptors as promising adsorbents of lanthanide from nonaqueous media or organic salts and also provides new opportunities for the investigation of the luminescence characteristics of lanthanide complexes in thin films.

Synthesis and Spectral Study of a New Family of 2,5-Diaryltriazoles Having Restricted Rotation of the 5-Aryl Substituent.

Efficient synthesis of 2,5-diaryl substituted 4-azido-1,2,3-triazoles by the reaction of sodium azide with dichlorosubstituted diazadienes was demonstrated. The optical properties of the prepared azidotriazoles were studied to reveal a luminescence maximum in the 360–420 nm region. To improve the luminescence quantum yields a family of 4-azido-1,2,3-triazoles bearing ortho-propargyloxy substituents in the 5 position was prepared. Subsequent intramolecular thermal cyclization permits to construct additional triazole fragment and obtain unique benzoxazocine derivatives condensed with two triazole rings. This new family of condensed heterocycles has a flattened heterocyclic system structure to provide more conjugation of the 5-aryl fragment with the triazole core. As a result, a new type of UV/“blue light-emitting” materials with better photophysical properties was obtained.