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Osteosarcoma is a primary bone malignancy with aggressive metastatic potential and poor prognosis rates. In our earlier work we have investigated the therapeutic potential of curcumin as an anti-invasive agent in osteosarcoma by its ability to regulate the Wnt/beta-catenin signaling pathway. However, the clinical use of curcumin is limited owing to its low potency and poor pharmacokinetic profile. In this study, an attempt was made to achieve more potent Wnt inhibitory activity in osteosarcoma cells by carrying out synthetic chemical modifications of curcumin. We synthesized a total of five series consisting of 43 curcumin analogs and screened in HEK293T cells for inhibition of beta-catenin transcriptional activity. Six promising analogs, which were 6.5- to 60-fold more potent than curcumin in inhibiting Wnt activity, were further assessed for their anti-invasive activity and Wnt inhibitory mechanisms. Western blot analysis showed disruption of beta-catenin protein nuclear translocation following treatment with analogs 2f, 3c and 4f. Using transwell assays, we also found that these compounds were more potent than 1a (curcumin) in impeding the invasion of osteosarcoma cells, possibly through suppressing MMP-9 activity. Structure-activity-relationship studies revealed that Wnt inhibitory effects could be enhanced by shortening and restraining the flexibility of the 7-carbon linker moiety connecting the terminal aromatic rings of curcumin and substituting both rings with appropriate substituents. Our results demonstrate that the synthesized curcumin analogs are more potent Wnt inhibitors in osteosarcoma cell lines as compared to parental curcumin and are good lead compounds for further development. Future in vivo tests with these compounds will define their therapeutic potentials as promising drug candidates for clinical treatment of osteosarcoma.

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Reference:
Synthesis and Crystal Structure of a Chiral C3-Symmetric Oxygen Tripodal Ligand and Its Applications to Asymmetric Catalysis,
Chiral lanthanide(III) complexes of sulphur–nitrogen–oxygen ligand derived from aminothiourea and sodium D-camphor-β-sulfonate

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An efficient double Michael addition of nitromethane to divinyl ketones was established in good to high yields (75?99%). A wide range of cyclohexanones were obtained with excellent diastereocontrol (up to >20:1 dr) and enantioinduction (91?99% ee) in a one-pot fashion. The involvement of basic additive significantly enhanced the reactivity of this cascade sequence.

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Reference:
Synthesis and Crystal Structure of a Chiral C3-Symmetric Oxygen Tripodal Ligand and Its Applications to Asymmetric Catalysis,
Chiral lanthanide(III) complexes of sulphur–nitrogen–oxygen ligand derived from aminothiourea and sodium D-camphor-β-sulfonate

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Cooperative activation by a soft bimetallic catalyst, a hard Bronsted acid, and a hard Bronsted base has allowed the formation of highly enantioenriched, diastereomerically pure masked alpha-amino acids with adjacent quaternary and tertiary stereocenters in a single reaction starting from racemic N-benzoylated amino acids. The products can, for example, be used to prepare bicyclic dipeptides.

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Reference:
Synthesis and Crystal Structure of a Chiral C3-Symmetric Oxygen Tripodal Ligand and Its Applications to Asymmetric Catalysis,
Chiral lanthanide(III) complexes of sulphur–nitrogen–oxygen ligand derived from aminothiourea and sodium D-camphor-β-sulfonate

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A practical, convenient, and safe cyano(nitro)methylation method was developed, in which cyano-aci-nitroacetate served as a synthetic equivalent of anionic nitroacetonitrile. A control of the single/double Michael additions was achieved, which enabled the synthesis of unsymmetrical double Michael adducts. Moreover, the Michael adducts can be used as precursors of pyridine and naphthyridine frameworks.

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Reference:
Synthesis and Crystal Structure of a Chiral C3-Symmetric Oxygen Tripodal Ligand and Its Applications to Asymmetric Catalysis,
Chiral lanthanide(III) complexes of sulphur–nitrogen–oxygen ligand derived from aminothiourea and sodium D-camphor-β-sulfonate

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(Chemical Equation Presented) A new, facile, efficient, “green” and chemoselective procedure for the synthesis of indole derivatives has been developed with pulverization-activation method catalyzed by Bi(NO 3)3·5H2O (PAMC- Bi(NO3) 3·5H2O) through grinding of indoles with aldehydes or Michael acceptors in the presence of catalytic amounts of Bi(NO 3)3·5H2O under solvent-free conditions.

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Reference:
Synthesis and Crystal Structure of a Chiral C3-Symmetric Oxygen Tripodal Ligand and Its Applications to Asymmetric Catalysis,
Chiral lanthanide(III) complexes of sulphur–nitrogen–oxygen ligand derived from aminothiourea and sodium D-camphor-β-sulfonate

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A novel direct transformation of hydrazones to acyloxylated pyrazoles by copper-catalyzed regioselective olefinic C(sp2)-H bond cycloamination and acyloxylation was performed under mild conditions, which combines the formation of the pyrazole skeleton and installation of an acyloxyl group in a single step, using facile carboxylic acids as the acyloxylation reagents.

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Reference:
Synthesis and Crystal Structure of a Chiral C3-Symmetric Oxygen Tripodal Ligand and Its Applications to Asymmetric Catalysis,
Chiral lanthanide(III) complexes of sulphur–nitrogen–oxygen ligand derived from aminothiourea and sodium D-camphor-β-sulfonate

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Amidinohydrazone compounds are very important synthetic intermediates and can serve as versatile precursors in synthesis of many natural products and drug molecules. The use of ultrasound, p-dodecylbenzenesulfonic acid (DBSA) and water as solvent improved the synthesis of different 2-(1,5-diaryl-1,4- pentadien-3-ylidene)-hydrazinecarboximidamide hydrochlorides. The best reaction conditions for the condensation of 1,5-diphenyl-1,4-pentadien-3-one with aminoguanidine hydrochloride were as follows: 1,5-diphenyl-1,4-pentadiene-3-one (1, 1 mmol), aminoguanidine hydrochloride (1.1 mmol), DBSA (0.5 mmol), water 10 mL, reaction temperature 25-27C, irradiation frequency 25 kHz. 2a was achieved in 94% yield within 2 h. The other seven amidinohydrazones were obtained in 84-94% yield within 2-3 h under the same conditions. Compared to the method involving catalysis by hydrochloric acid in refluxing EtOH, the advantages of present procedure are milder conditions, shorter reaction times, higher yields, and environmental friendly conditions, which make it a useful strategy for the synthesis of analogues.

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Reference:
Synthesis and Crystal Structure of a Chiral C3-Symmetric Oxygen Tripodal Ligand and Its Applications to Asymmetric Catalysis,
Chiral lanthanide(III) complexes of sulphur–nitrogen–oxygen ligand derived from aminothiourea and sodium D-camphor-β-sulfonate

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New 6-amino and 6,8-diamino-2-aryl-2,3-dihydro-4-styryl-1H- pyrimido[4,5-b][1,4]diazepines were obtained in the reaction of 2,4,5,6-tetraaminopyrimidine 1a and 4,5,6-triaminopyrimidine 1b with one equivalent of the diarylideneacetones 2 in absolute ethanol with acetic acid as the catalyst. Structure analysis of 6-amino and 6,8-diamino-2-aryl-2,3-dihydro-4-styryl-1H- pyrimido[4,5-b][1,4]diazepines 3a-i, determined by detailed nmr measurements, reveals a high regioselectivity of this reaction.

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Reference:
Synthesis and Crystal Structure of a Chiral C3-Symmetric Oxygen Tripodal Ligand and Its Applications to Asymmetric Catalysis,
Chiral lanthanide(III) complexes of sulphur–nitrogen–oxygen ligand derived from aminothiourea and sodium D-camphor-β-sulfonate

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Diazaspiro[5.5]undecane-1,3,5,9-tetraones and 3-thioxo-diazaspiro[5.5]undecane-1,5,9-trione have been synthesized via double Michael addition of 1,5-diphenyl-1,4-pentadien-3-one with active methylene heterocycles N,N-dimethyl barbituric acid, barbituric acid and thiobarbituric acid in water:ethanol (1:1) using TBAB as catalyst. The solvent effect on photophysical behavior of these compounds showed that stokes shift increases with increase in polarity of solvents. The solvent effect on the spectral properties has been investigated by using the Lippert-Mataga and Reichardt methods. The solvatochromism is analyzed by linear solvation energy relationship using the new four-parameter Catalan polarity scales. The relative fluorescence quantum yield of these diazaspiro compounds varies in solvents of different polarity. The HOMO and LUMO energies have been calculated by TDDFT (B3LYP/6-311G (d, p)) approach. TDDFT calculations were also used to compare the experimental and theoretical absorption spectra.

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Reference:
Synthesis and Crystal Structure of a Chiral C3-Symmetric Oxygen Tripodal Ligand and Its Applications to Asymmetric Catalysis,
Chiral lanthanide(III) complexes of sulphur–nitrogen–oxygen ligand derived from aminothiourea and sodium D-camphor-β-sulfonate

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Photoexcitation of dibenzalacetones (1a-d) in homogeneous media and solid state yields a mixture of products with poor conversions. Irradiation of the reactants complexed to gamma-cyclodextrin predominantly affords a single dimer (syn adduct 6) despite the possibility for several monomeric and dimeric products. High selectivity in the cavitand-mediated reaction along with the structural characterization of the inclusion complex provides insight into the supramolecular interactions that drive the self-assembly of the host-guest system.

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Reference:
Synthesis and Crystal Structure of a Chiral C3-Symmetric Oxygen Tripodal Ligand and Its Applications to Asymmetric Catalysis,
Chiral lanthanide(III) complexes of sulphur–nitrogen–oxygen ligand derived from aminothiourea and sodium D-camphor-β-sulfonate