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Thioacids and thioamino acids were synthesized in excellent yields from readily available acyl benzotriazoles and sodium hydrosulfide in water at room temperature. The new methodology features mild reaction conditions, high yields, short reaction times, and does not involve the use of organic solvents or bases. The reaction is eco-friendly, and the workup procedure is simple and does not require chromatographic separation.

A novel anil compounds, 1-{(Z)-[(3,5dimethylphenyl)imino]methyl}naphthalen-2-ol (HNMA) and 5- (diethylamino) -2- {(Z)- [(3,5-dimethylphenyl)imino] methyl} phenol (DMSMA), were prepared and characterized on the basis of elemental analyses, X-ray, 1H NMR, 13C NMR, UV–Vis and IR spectral data. Their inhibiting performance for mild steel in 0.5 M H2SO4 solution was evaluated by a series of techniques including potentiodynamic polarization, electrochemical impedance spectroscopy, scanning electronic microscope (SEM), energy-dispersive X-ray spectroscopy (EDX) and theoretical calculations. Findings show that HNMA and DMSMA act as good inhibitors, and their inhibition efficiency increases with increasing their concentration. Polarization data suggested that the Schiff bases molecules used as mixed type inhibitors. Impedance measurements indicating that the corrosion reaction is controlled by charge transfer process. The adsorption of HNMA and DMSMA on the metal surface was found to obey Langmuir adsorption isotherm. Furthermore, theoretical study gives insightful explanations of the inhibition mechanism.

Three novel peptidomimetic cationic surfactants were synthesized in good yields. The chemical configurations of these surfactants were clarified using 1H, 13C NMR and FT-IR spectroscopy. The inhibition capacity and adsorption performance of these compounds on C-steel were studied by electrochemical techniques (Electrochemical impedance spectroscopy (EIS) and Potentiodynamic polarization (PDP) methods). The prepared compounds demonstrated outstanding protection power for the erosion of C-steel in 0.5 M HCl at 323 K. The PDP studies demonstrated that the novel surfactants behaved as mixed-type additives. The protection capacity rises with an increasing surfactant dose, with values ranging from 93.10 to 98.25% at 100 ppm. The adsorption of additives on the electrode interface follows the Langmuir model and contains chemisorption modes. The Monte Carlo (MD) simulations and density functional theory (DFT) calculations support the experimental findings and provide insight into the understanding of the adsorption features and protection performance mechanisms of the examined surfactants.

Herein, we describe the design and synthesis of new benzenesulfonamide derivatives as selective COX-2 inhibitors based on bumetanide scaffold. Benzenesulfonamides bearing both the pyrazole 6b and the triazoles 9a, 9c were good inhibitors of COX-2 with IC50 values of 0.32, 0.28 and 0.17 µM, respectively. These benzenesulfonamides 6b, 9a and 9c exhibited a higher selectivity index than the reference drug celecoxib. Molecular modeling study showed that incorporation of bumetanide led to a unique binding mode that is most likely the reason for the observed significant COX-2 selectivity. The anti-inflammatory activity of synthesized compounds revealed that triazoles 9a and 9c demonstrated higher efficacy than celecoxib upon using in vivo carrageenan-induced rat paw edema model. Most of the prepared compounds possess low ulcerogenic potential when administered orally. Therefore, these compounds have a great potential to be developed as safe therapeutics for inflammation, pain, and other diseases where COX-2 plays important role in their pathophysiology.

SummaryMalignant cells exhibit aerobic glycolysis (the Warburg effect) and become dependent on de novo lipogenesis, which sustains rapid proliferation and resistance to cellular stress. The nuclear receptor liver-X-receptor (LXR) directly regulates expression of key glycolytic and lipogenic genes. To disrupt these oncogenic metabolism pathways, we designed an LXR inverse agonist SR9243 that induces LXR-corepressor interaction. In cancer cells, SR9243 significantly inhibited the Warburg effect and lipogenesis by reducing glycolytic and lipogenic gene expression. SR9243 induced apoptosis in tumors without inducing weight loss, hepatotoxicity, or inflammation. Our results suggest that LXR inverse agonists may be an effective cancer treatment approach.

In this work, two dispiro[3H-indole-3,2′-pyrrolidine-3′,3″-piperidines], C31H29Cl2N3O3 (4a) and C32H31Cl2N3O3 (4b), have been synthesized and characterized by IR, 1H NMR, 13C NMR, 1H 1H COSY, 1H 13C HSQC and single crystal X-ray diffraction. Both compounds were found to be crystallized in the triclinic space group P 1 ¯ with Z = 2. Molecules of the crystalline structure of 4a are linked with intermolecular C H⋯O and N H⋯O hydrogen bonding. Meanwhile, an intermolecular N H⋯O hydrogen bonding was recognized in the crystalline structure of 4b. Molecular mechanics force field (MM+), followed by either semi-empirical AM1 or PM3, has been used to calculate the optimized geometrical parameters for the two compounds. The determined theoretical geometry parameters were found to be in a good agreement with the parameters obtained using X-ray studies. Moreover, the Molecular Electrostatic Potential (MEP) of both compounds have been calculated at B3LYP/6-31G(d,p) level of theory exhibiting that, the most electrophilic site of the synthesized compounds, is the piperidone O3 atom however, the most nucleophilic site is the indolyl N2. Additionally, the Frontier Molecular Orbitals (FMOs) 4a and 4b have been determined by the same technique exhibiting large energy gap between HOMO and LUMO orbitals (3.40, 3.43 eV for 4a and 4b, respectively), inferring good stability, high excitation energies and large chemical hardness of these molecules.

Pyrrolizine derivatives constitute a class of heterocyclic compounds which can serve as promising scaffolds for anticancer drugs. The unique antitumor properties of mitomycin C inspired chemists to develop different pyrrolizine systems and assess their potential antitumor activities against a wide variety of cancer types. Here we review the different classes of pyrrolizines that possess anticancer potency, with an emphasis on their structure activity relationships, in an effort to pave the way for further development in this promising area of research.

The structure–activity relationship study of a diphenylpropanamide series of ROR-γ selective modulators is reported. Compounds were screened using chimeric receptor Gal4 DNA-binding domain (DBD)-NR ligand binding domain cotransfection assay in a two-step format. Three different regions of the scaffold were modified to assess the effects on repression of ROR-γ transcriptional activity and potency. The lead compound 1 exhibits modest mouse pharmacokinetics and an acceptable in vitro profile which makes it a suitable in vivo probe to interrogate the functions of ROR-γ in animal models of disease.

Reactions of readily available and stable 1-(α-alkoxyalkyl)benzotriazoles type 9a,b and 10a–d with a variety of silyl enol ethers 11 or 1,3-dicarbonyl compounds 13 give the expected ketones 12a–l (60–92%), β-keto esters 14a,b (62–67%), and malonates 14c,d (79–88%) in which a tetrahydrofuran or tetrahydropyran moiety has been introduced at the α position. 1-(Benzotriazol-1-yl)alkyl esters 7 are converted by cyanide anion into cyanohydrin esters 15a–i (55–98%).