One-pot three-component azide-alkyne cycloaddition: Synthesis of new pyrazole, 1,2,3-triazole,and oxadiazole tethered and their anti-inflammatory,quantitative structure-activity relationship,and docking studies

A simple and efficient one-pot three-component azide-alkyne cycloaddition of 5-chloro-1-phenyl-pyrazole-4-carbaldehyde with 2-(prop-2-yn-1-ylthio)-5-(substituted phenoxy)methyl-1,3,4-oxadiazole and sodium azide is reported. The newly synthesized compounds were characterized by spectral and analytical data. They were screened for in vitro anti-inflammatory activity by bovine serum albumin denaturation assay. All the tested compounds showed moderate anti-inflammatory activity, whereas three compounds ( 4d , 4i , and 4k ) showed excellent activity comparable with that of the standard drug diclofenac sodium. The quantitative structure-activity relationship (QSAR) study was carried out for anti-inflammatory activities of the synthesized compounds and developed a QSAR model. Inspired by their in vitro anti-inflammatory activities, they were docked to the active site of COX-2 to know the anti-inflammatory potency in silico.     

Ionic liquid mediated synthesis and in vitro mechanistic exploration of polycyclic cage-like heterocyclic hybrid

A three-component, [3 + 2]-cycloaddition/annulation domino protocol is described for the synthesis in excellent yield of a polycyclic cage-like heterocyclic hybrid (PCHH) that comprises various advantaged structural units viz., α,β-unsaturated ketone moiety, 4-pyridinone and pyrroloisoquinoline in a cage-like framework. The antitumor activity of PCHH on human breast (MCF7), colon (HCT116), cervical (JURKAT) and lung (NCI-H460) malignant cell lines inhibited the propagation of all cell lines. This hybrid molecule displayed increased broad-spectrum anticancer activity with higher doses of PCHH. Furthermore, the compound induced 45.21% of early apoptosis and 46.32% of late apoptosis in the Jurkat cancer cell line. Cell cycle analysis showed that this cage-like compound caused cell cycle arrest of Jurkat cells at the S phase and sub G0/G1 phase. Additionally, it led to increased DNA fragmentation and mitochondrial membrane permeabilization through activation of caspase-3 enzyme. Present investigation demonstrates the specific cytotoxic activity of the cage-like compound and the induction of apoptosis through the intrinsic pathway of Jurkat cells.     

Inhibition of Thiol-Mediated Uptake with Irreversible Covalent Inhibitors

Thiol-mediated uptake is emerging as method of choice to penetrate cells. This study focuses on irreversible covalent inhibitors of thiol-mediated uptake. High-content high-throughput screening of the so far largest collection of hypervalent iodine reagents affords inhibitors that are more than 250 times more active than Ellman’s reagent and rival the best dynamic covalent inhibitors. Comparison with other irreversible reagents reveals that inhibition within one series follows reactivity, whereas inhibition across series deviates from reactivity. These trends support that molecular recognition, besides dynamic covalent exchange, contributes significantly to thiol-mediated uptake. The most powerful inhibitors besides the best hypervalent iodine reagents were Fukuyama’s nosyl protecting group and super-cinnamaldehydes that have been introduced as irreversible activators of the pain receptor TRPA1. Considering that several viruses use different forms of thiol-mediated uptake to enter cells, the identification of new irreversible inhibitors of thiol-mediated uptake is of general interest for the discovery of new antivirals.     

Synthesis and Biological Studies of O3-Aryl Galactosides as Galectin Inhibitors

β-Galactose derivatives have recently been reported to selectively inhibit galectin-3, and a library of O3-arylated galactosides with varying substitution patterns was designed to study such inhibitions further. The O3-arylated galactosides were synthesized using diaryliodonium salts under mild and transition metal free conditions, providing the target products in moderate to good yields. An O3-trifluoroethylated galactoside was also synthesized using iodonium salt chemistry. Azido-substituted products were subsequently transformed into the corresponding triazoles. After deprotection, a selection of galactoside derivatives were evaluated for inhibitory potencies against galectins-1, 3, 4 N (N-terminal domain), 4 C (C-terminal domain), 7, 8 N, 8 C, 9 N, and 9 C and one compound with promising affinity and selectivity for both the N- and C-terminal domain of galectin-9 was discovered.     

Chemical Composition and Antioxidant Activity of the Leaf Essential Oil of Schefflera venulosa

Chemistry of Natural Compounds -     

Brønsted acid catalyzed synthesis of 2-aryl-quinazolinones via cyclization of 2-aminobenzamide with benzonitriles in PEG

A simple and efficient Brønsted acid catalyzed synthesis of 2-aryl-quinazolinones via cyclization of 2-aminobenzamides with benzonitrile in PEG under metal and ligand-free condition. All substituted benzonitriles were also well participated with the formation of the corresponding products in moderate to good yields.     

Thermodynamic Modeling of Nitric Acid Speciation Using eUNIQUAC Activity Coefficient Model

Journal of Solution Chemistry - The speciation of nitric acid was modeled using eUNIQUAC activity coefficient model and the thermodynamic dissociation constant was estimated by solving the...     

Physico-Chemical Characterization of Binary and Ternary Mixtures of Imidazolium Based Cation and Common Anion Ionic Liquids with Lactams

Journal of Solution Chemistry - Excess molar volumes, $$V_{{}}^{{\text{E}}}$$ , excess isentropic compressibilities, $$\kappa_{{\text{S}}}^{{\text{E}}}$$ of binary 1-butyl-2,3-dimethylimidazolium...     

Greener approach toward synthesis of biologically active s-Triazine (TCT) derivatives: A recent update

The greener methodology to synthesize s-triazine derivatives (also known as TCT) is described, including synthesis through microwave, ultrasound, and solvent-free conditions. This review mainly focuses on reactions of TCT (2,4,6-trichloro-1,3,5-triazine) with various substituents having amine and hydroxy functionalities to give corresponding triazine derivatives under a greener approach. The results of reactions indicate that, unlike classical methods, green methods result in better yields of the product, through a rapid reaction, under mild reaction conditions, and by easy workup procedures.     

2- and 2,7-Substituted para-N-Methylpyridinium Pyrenes: Syntheses,Molecular and Electronic Structures,Photophysical, Electrochemical,and Spectroelectrochemical Properties and Binding to Double-Stranded (ds) DNA

Two N-methylpyridinium compounds and analogous N-protonated salts of 2- and 2,7-substituted 4-pyridyl-pyrene compounds were synthesised and their crystal structures, photophysical properties both in solution and in the solid state, electrochemical and spectroelectrochemical properties were studied. Upon methylation or protonation, the emission maxima are significantly bathochromically shifted compared to the neutral compounds, although the absorption maxima remain almost unchanged. As a result, the cationic compounds show very large apparent Stokes shifts of up to 7200 cm⁻¹. The N-methylpyridinium compounds have a single reduction at ca. −1.5 V vs. Fc/Fc⁺ in MeCN. While the reduction process was reversible for the 2,7-disubstituted compound, it was irreversible for the mono-substituted one. Experimental findings are complemented by DFT and TD-DFT calculations. Furthermore, the N-methylpyridinium compounds show strong interactions with calf thymus (ct)-DNA, presumably by intercalation, which paves the way for further applications of these multi-functional compounds as potential DNA-bioactive agents.