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2,6-Bis(4-iodophenyl)-4-(4-trifluoromethylphenyl)pyridine, as a new aromatic diiodide compound, was synthesized through a one-pot protocol by the sequential diazotization-iodination of 2,6-bis(4-aminophenyl)-4-(4-trifluoromethylphenyl)pyridine with KI/NaNO2/ p -TsOH in acetonitrile at room temperature. A number of new aromatic fluorinated poly(pyridine amide)s containing 2,6-diphenyl-4-(4-trifluoromethylphenyl)pyridine units were prepared via a Pd(PPh3)2Cl2 catalyzed carbonylation polymerization of this diiodide, diamines and carbon monoxide in DMAc in the presence of PPh3 and 1,8-diazabicyclo[5,4,0]-7-undecene. These new polyamides with inherent viscosities of 0.63–0.72 dL/g were amorphous and easily soluble in amide type aprotic solvents such as NMP, DMAc, DMF and dimethyl sulfoxide at room temperature. Thermal analysis data up to 800°C in nitrogen showed their high thermal behavior with 5% weight loss temperature of 428–498°C and char yield of 62–69%. Their limiting oxygen index of 42.3–45.1 showed that the resulting poly(pyridine amide)s could be classified as "self-extinguishing polymers". Also, their thin films exhibited high optical transparency with a cut-off wavelength of 324–373 nm. [ABSTRACT FROM AUTHOR]

We recently reported that synthetic derivatives of rutaecarpine alkaloid exhibited high acetyl cholinesterase (AChE) inhibitory activity and high selectivity for AChE over butyrylcholinesterases (BuChE). To explore novel effective drugs for the treatment of Alzheimer's disease (AD), in this paper, further research results were presented. Starting from a structure-based drug design, a series of novel 2-(2-indolyl-)-4(3 H)-quinazolines derivates were designed and synthesized as the ring-opened analogues of rutaecarpine alkaloid and subjected to pharmacological evaluation as AChE inhibitors. Among them, derivates 3a-c and 3g-h exhibited strong inhibitory activity for AChE and high selectivity for AChE over BuChE. The structure-activity relationships were discussed and their binding conformation and simultaneous interactions mode were further clarified by kinetic characterization and the molecular docking studies. [ABSTRACT FROM AUTHOR]

In this paper, we report a morphology controllable and energetically efficient route to prepare blue-emitting BaMgAl10O17:Eu2+ (BAM) phosphor, a hydrothermal homogeneous precipitation/calcinations method. Utilizing a urea homogeneous hydrolysis reaction within a sealed hydrothermal container with self-generated pressure, well-crystallized BAM with regular morphologies was obtained at a urea dosage of nurea: ncations = 7.5 and a calcining temperature of 1200 °C. The as-prepared phosphor was granular in shape and had an average particle size of about 0.1 µm without using any additional agents. With the template-directed function of polyethylene glycol or β-cyclodextrin, the as-prepared phosphors respectively, had rod-like and flake-like shapes. According to the photoluminescent results, rod-like or flake-like BAM showed similar luminescent characteristics with granular BAM except slightly stronger luminescent intensity. When the calcining temperature was raised to 1400 °C, the emission intensity of the sample prepared by hydrothermal homogeneous precipitation was stronger than that of commercial BAM. [ABSTRACT FROM AUTHOR]

A novel series of N, N′-bis-methylenedioxybenzyl-alkylenediamines 5a- 5g have been designed, synthesized and evaluated as bivalent anti-Alzheimer's disease ligands. The enzyme inhibition assay results indicated that compounds 5e- 5g inhibit both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in the micromolar range (IC50, 2.76-4.24 µM for AChE and 3.02-5.14 µM for BuChE), which was in the same potential as the reference compound rivastigmine (IC50, 5.50 µM for AChE and 1.60 µM for BuChE). It was found that compounds could bind simultaneously to the peripheral and catalytic sites of AChE. β-Amyloid (Aβ) aggregation inhibition assay results showed that compound 5e exhibited highest self-mediated Aβ fibril aggregation inhibition activity (40.3%) with a similar potential as curcumin (41.6%). It was also found that 5e- 5g did not affect neuroblastoma cell viability at the concentration of 50 μM. [ABSTRACT FROM AUTHOR]

A novel method for the synthesis of tetrahydropyridine-fused 1,3-diazaheterocycles was developed via the reaction of heterocyclic ketene aminals (HKAs) with Baylis-Hillman acetates (B-H acetates). [ABSTRACT FROM AUTHOR]

A simple method for the synthesis of polyfunctionalized pyridine-fused 1,3-diazaheterocycles has been developed via reaction of heterocyclic ketene aminals (HKAs) with bis(methyl�thio)methylene malononitrile. [ABSTRACT FROM AUTHOR]

α-Hypervalent iodo functionalized phosphonium and arsonium ylides 2 can be used as umpolung ylides to react with nucleophiles to give α-heteroatom substituted ylides 4 in good yields. A tandem sequence of nucleophilic substitution then Wittig reaction occurs smoothly to form (Z)-α-halo-α,β-unsaturated esters 6, stereoselectively, in moderate to excellent yields. [Copyright &y& Elsevier]

Abstract: A series of mansonone F (MF) derivatives were designed and synthesized. These compounds were found to be strong inhibitors for topoisomerases, with much more significant inhibition for topoisomerase II rather than topoisomerase I. The best inhibitor showed 20 times stronger anti-topoisomerase II activity than a positive control Etoposide. The cytotoxic activity of these MF derivatives was evaluated against human cancer cell lines CNE-2 and Glc-82, which showed that these compounds were potent antitumor agents. The structure–activity relationships (SARs) study revealed that o-quinone group and pyran ring are important for their cytotoxic activity. [Copyright &y& Elsevier]

Abstract Drug-resistant bacteria associated with biofilm formation are rapidly on the rise, requiring novel therapeutic options to combat biofilm induced drug-resistance. In this study, a class of 3-hydroxy-2-(phenylhydroxy-methyl)-6-methyl-4 H -pyran-4-one derivatives (1a - 1e) were found by screening of an in-house compound library to be potential Pseudomonas aeruginosa biofilm inhibitors. Thirty one novel 2-substituted 3-hydroxy-6-methyl-4 H -pyran-4-one derivatives were synthesized and assayed for their biofilm inhibitory activity. A promising biofilm inhibitor 6a was identified, and showed an obvious biofilm inhibitory effect even at a concentration of 2.5 μM. Further mechanism studies revealed that 6a only shows inhibitory effects on the expression of pqsA-gfp in a fluorescent reporter strain, and the production of a PQS- regulated virulence factor, pyocyanin. This indicates that this type of compound exercises its anti-biofilm activity specifically through the PQS pathway. Novel chemical biofilm inhibitors are described here and guard against biofilm formation associated with Pseudomonas aeruginosa infections. Graphical abstract Image 1 Highlights • Four series of 2-substituted 3-hydroxy-6-methyl-4 H -pyran-4-one derivatives were synthesized. • Potent biofilm inhibitor 6a exhibited excellent Pseudomonas aeruginosa biofilm inhibitory effect were identified. • The PQS pathway specific anti-biofilm mechanism of this type of compound was uncovered. [ABSTRACT FROM AUTHOR]

Obesity, a global pandemic posing a growing threat to human health, necessitates the development of effective and safe anti-obesity agents. Our previous studies highlighted the lipid-lowering effects of indolylquinazoline Bouchardatine and its derivatives. In this study, we employed scaffold hopping and simplification strategies to design and synthesize two new series derivatives by modifying the D ring. Extensive discussions have been conducted regarding the structure-activity relationship between lipid-lowering activity and the new compounds. These discussions have resulted in the discovery of 2-pyrimidinylindole derivatives as a promising scaffold for anti-obesity treatment. The new 2-pyrimidinylindole derivatives exhibited comparable lipid-lowering activity to the previously reported indolylquinazoline derivatives, including SYSU-3d and R17 , with reduced toxicity. The most potent compound, 5a , demonstrated a larger therapeutic index, improved aqueous solubility and oral bioavailability compared to the previous lead compounds. In vivo evaluation indicated that 5a effectively reduced lipid accumulation in adipose tissue, improved glucose tolerance, and mitigated insulin resistance and liver function damage caused by a high-fat and high-cholesterol diet. Mechanism studies indicated that 5a may regulate lipid metabolism through the modulation of the PPARγ signaling pathway. Overall, our study has identified a highly active compound 5a , and provided the basis for further development of 2-pyrimidinylindole as a promising scaffold for obesity treatment. [Display omitted] • Novel pyrimidinylindole derivatives have been developed as potential anti-obesity agents through the modification of indoloquinazoline. • The SAR was explored and promising compound 5a was figured out. • 5a could attenuate HFC-induced obesity and related metabolic syndrome. • 5a may regulate lipid metabolism through the modulation of the PPARγ signaling pathway. • 5a exhibits favorable water solubility and oral bioavailability, thereby presenting valuable avenues and prospects for future applications. [ABSTRACT FROM AUTHOR]

Abstract: Ca10(PO4)6(OH)2 (HAP) and NH4Al(OH)2CO3·H2O (AACHH) whiskers were prepared by a homogeneous precipitation method based on urea hydrolysis reaction. To clarify the growth process of whiskers in the homogeneous system, XRD and SEM results of the products obtained at different reaction time were investigated in detail. A novel observation about budding growth in preparing both whiskers was described. It was indicated that the growth of whiskers went through three stages, which were oversaturation, nucleation, and budding growth. The growth units of whiskers budded from the surfaces of substrates, which were crystallized flakes for HAP preparation and amorphous spherical nuclei for AACHH preparation. Subsequently, the whiskers grew up accompanying with the disappearing substrates. One-dimensional whiskers with fine morphology and large slenderness ratio were finally obtained. Besides, according to the crystal growth and the interface diffusion theories, the effects of the templates and the budding growth mechanism were discussed. [Copyright &y& Elsevier]

Abstract: A novel route for the efficient synthesis of a target psoralen moiety, 4,4′-dimethylxanthotoxol, has been developed, which need only four steps using cheap pyrogallol as a starting material. Subsequently, a range of new glycosylated psoralen derivatives were synthesized in good yields with simple procedures and mild reaction conditions. The experiment of biological activity shows that some of the glycosylated psoralen derivatives have antiproliferative activities against human cancer cell lines. A strong photo-induced antiproliferative effects were found under UVA. All of the glycosylated psoralen derivatives exhibited antioxidant activities against the oxidation of DNA induced by Cu2+/glutathione (GSH). Further experiment also demonstrates that the introduction of sugar moieties in some glycosylated psoralen derivatives can improve their antioxidant activities significantly. [Copyright &y& Elsevier]

Abstract: A series of dual binding site acetylcholinesterase (AChE) inhibitors have been designed, synthesized, and tested for their ability to inhibit AChE, butyrylcholinesterase (BChE), AChE-induced and self-induced β-amyloid (Aβ) aggregation. The new hybrids consist of a unit of 1-azabenzanthrone and a tacrine or its congener, connected through an oligomethylene linker containing an amine group at variable position. These hybrids exhibit high AChE inhibitory activity with IC50 values in the nanomolar range in most cases. Moreover, five out of the 12 hybrids of this series, particularly those bearing a tetrahydroacridine moiety, exhibit a significant in vitro inhibitory activity toward the AChE-induced and self-induced Aβ aggregation, which makes them promising anti-Alzheimer drug candidates. [Copyright &y& Elsevier]

Abstract: A series of quinolino-benzo-[5, 6]-dihydroisoquindolium compounds (3a, 3f, 3g, and 3j) derived from alkaloid berberine were designed and synthesized as novel G-quadruplex ligands. Subsequent biophysical and biochemical evaluation demonstrated that the addition of pyridine ring and amino group into berberine improved the binding ability and selectivity towards G-quadruplex DNA in comparison with the previously reported 9-N-substituted berberine derivatives. Furthermore, qRT-PCR assay showed compound 3j led the down-regulation of c-myc gene transcription in leukemia cell line HL60, while little effect on normal cell line ECV-304, which was consistent with the behavior of an effective G-quadruplex ligand targeting c-myc oncogene. [Copyright &y& Elsevier]

Abstract: A series of graveoline and graveolinine derivatives were synthesized. The biological results showed that most of graveoline derivatives possessed higher cytotoxicity and better inhibitive effect against the adhesion and migration of human umbilical vein endothelial cell (HUVEC) than graveolinine derivatives. Among these compounds, 8d was the most potent agents that also showed significant anti-angiogenesis activities in chick embryo chorioallantoic membrane (CAM) assay. [ABSTRACT FROM AUTHOR]

Abstract: A series of novel rutaecarpine derivatives and related alkaloid derivatives 3-aminoalkanamido-substituted rutaecarpine 4a–f and 7,8-dehydrorutaecarpine 5a–c, and 6-aminoalkanamido-substituted 3-[2-(3-Indolyl)ethyl]-4(3a)-quinazolinones 8a–c, were synthesized and subjected to pharmacological evaluation as acetylcholinesterase (AChE) inhibitors. The synthetic compounds exhibited strong inhibitory activity for AChE and high selectivity for AChE over BuChE. The structure–activity relationships were discussed and their binding conformation and simultaneous interactions mode were further clarified by kinetic characterization and the molecular docking studies. [Copyright &y& Elsevier]

Abstract: A series of icariin derivatives were synthesized. Their multidrug resistance (MDR) reversal activities were evaluated by MTT assay and the results indicated that the derivatives were the potent modulators of MDR. It was showed that the derivatives significantly increased the intracellular accumulation of ADR in MCF-7/ADR cells compared with drug sensitive MCF-7 cells. The results of bi-directional assay and reverse transcription polymerase chain reaction (RT-PCR) assay showed that the derivatives had high inhibitory activity against P-gp efflux function and significantly down-regulated on the expression of P-gp. [Copyright &y& Elsevier]

Abstract: Aporphine alkaloids, isolated from Chinese medicinal herb, are important natural products. We recently reported that synthetic derivatives of oxoisoaporphine alkaloids exhibited high acetylcholinesterase inhibitory activity and high selectivity for AChE over BuChE (Bioorg. Med. Chem. Lett. 2007, 17, 3765–3768). In this paper, further research results were presented. A series of novel derivatives of oxoaporphine alkaloids (5a–j, 4-carboxylic amide-7-oxo-7H-dibenzo[de,g]quinoline, Ar-CONH(CH2)nNR) and their quaternary methiodide salts (6a–h, Ar-CONH(CH2)nN+(CH3)RI−) were designed and synthesized as acetylcholinesterase (AChE) and/or butyrylcholinesterase (BuChE) inhibitors. The AChE inhibition potency of synthetic oxoaporphine derivatives was decreased about 2–3 orders of magnitude as compared with that of oxoisoaporphine derivatives. Non-competitive binding mode was found for both kinds of derivatives. Molecular docking simulations on the oxoisoaporphine derivatives 7 series and oxoaporphine derivatives 6 series with AChE from Torpedo californica have demonstrated that the ligands bound to the dual-site of the enzyme. [Copyright &y& Elsevier]

Abstract: A series of 9-N-substituted berberine derivatives (2a–j) were synthesized and evaluated as a new class of G-quadruplex binding ligands. G-quadruplex of DNA had been proven to be the transcription controller of human c-myc gene. The interaction of 9-N-substituted berberine derivatives with G-quadruplex DNA in c-myc was examined via EMSA, CD spectroscopy, FRET-melting method, PCR-stop assay, competitive dialysis, cell proliferation assay, and RT-PCR assay. The experiment results indicated that these derivatives could selectively induce and stabilize the formation of intramolecular parallel G-quadruplex in c-myc, which led to down-regulation of transcription of the c-myc in the HL60 lymphomas cell line. The related structure–activity relationships were also discussed. [Copyright &y& Elsevier]

Abstract: A series of novel oxoisoaporphine alkaloid derivatives, 9-aminoalkanamido-1-azabenzanthrone (general formula Ar–NHCO(CH2) n NR2, Ar=1-azabenzanthrone, n =1, 2 or 3), had been synthesized. Compared with 1-azabenzanthrone, the derivatives had significantly higher DNA binding affinity with calf thymus DNA, and higher potent cytotoxicity against different tumor cell lines. The cytotoxicity and the structure–activity relationship of the prepared compounds were studied. The derivatives with two methylene groups (n =2), and piperidine or ethanolamine functional group in the side chain exhibited highest DNA binding affinity and cytotoxicity. [Copyright &y& Elsevier]

Abstract: The interaction of berberine and its 9-substituted derivatives with human telomeric DNA d[G3(T2AG3)3](telo21) has been investigated via CD spectroscopy, fluorescence spectroscopy, PCR-stop assay, competitive dialysis, and telomerase repeat amplification protocol (TRAP) assay. The results indicated that these semisynthesized compounds could induce and stabilize the formation of anti-parallel G-quadruplex of telomeric DNA in the presence or absence of metal cations. Compared with berberine, the 9-substituted derivatives exhibit stronger binding affinity with G-quadruplex and higher inhibitory activity for telomerase. Introduction of a side chain with proper length of methylene and terminal amino group to the 9-position of berberine would significantly strengthen the binding affinity with G-quadruplex, resulting in increasing inhibitory effects on the amplification of telo21 DNA and on the telomerase activity. [Copyright &y& Elsevier]

Abstract: A series of 9-aminoalkanamido-1-azabenzanthrones derviatives (3a–i Ar–NHCO(CH2) n NR1R2) and their quaternary methiodide salts (4a–g Ar–NHCO(CH2) n N+(CH3)R1R2I−) were designed and synthesized as acetylcholinesterase (AChE) or butyrylcholinesterase (BuChE) inhibitors. The synthetic compounds exhibited high AChE inhibitory activity with IC50 values in the nanomolar range and high selectivity for AChE over BuChE (45- to 1980-fold). The structure–activity relationships (SARs) were discussed. [Copyright &y& Elsevier]

Abstract: A series of novel calix[4]arenocrowns 1a–c were efficiently synthesized by a one-pot reaction of calix[4]monohydroquinone diacetate 5 with ditosylate 6 and its analogues in the presence of sodium hydroxide. It was found that the calix[4]arenocrowns could form stable pseudorotaxane-type complexes 2a–c with paraquat, and further self-assemble into calix[4]areno[2]catenanes 3a–c with dicationic salt 8 and p-bis(bromomethyl)benzene. [Copyright &y& Elsevier]

Abstract: A series of tri-O-alkylated inherently chiral fluorescent calix[4]crowns in the cone conformations and a series of tetra-O-alkylated inherently chiral fluorescent calix[4]crowns in the partial cone conformations have been synthesized. By condensing with chiral auxiliary (S)-BINOL, the resulting diastereomers could be separated via preparative TLC. We found that the size of the crown moiety effected the separation of the diastereomers. Further, removal of the BINOL unit by hydrolysis furnished pairs of enantiomers with optical purity. Moreover, we found that a tetra-O-alkylated inherently chiral fluorescent calix[4]crown-6 in the partial cone conformation 6c showed considerable enantioselective recognition capability towards chiral leucinol. [Copyright &y& Elsevier]

Abstract: The synthesis, structure and ring-closing metathesis (RCM) reactions of polyether bridged biscalix[4]arenes 6 in the partial cone conformation with upper rim allyl substituents are reported. The RCM reaction modes depend on the length of polyether chain. Diethylene glycolic chain produced the dimer 7a and linear oligomer 7a′ with multi-cavities, whereas triethylene and tetraethylene glycolic chains allowed direct cyclization through intramolecular head-to-tail pattern to yield novel bridged biscalix[4]arenes 7b–c. [Copyright &y& Elsevier]

A family of novel calix[4]arene derivatives containing nucleoside bases were designed and synthesized. Coupling reaction between para mono- or bis-amino calix[4]arenes 5, 6 or 7 and thymin-1-ylacetic acid in the presence of DCC afforded mono- or bis-thymine-substituted calix[4]arenes 8, 9 or 10 in over 70% yield. Owing to the low solubility of adenine-N9-ylacetic acid in DMF and DMSO and the weak nucleophilicity of aminocalix[4]arene derivatives, alternatively, the substitution reaction of bromoacetylated aminocalix[4]arenes derivatives 11, 12, 13 with adenine in the presence of sodium hydride was carried out to synthesize mono- or bis-adenine-substituted calix[4]arenes. Two kinds of isomers 15 and 16 or 17 and 18 were obtained due to the non-regiospecific alkylation of adenine, and their structures have been confirmed by 13C NMR and 1H NMR spectra. [Copyright &y& Elsevier]

Discovery of novel anti-obesity agents is a challenging and promising research area. Based on our previous works, we synthesized 40 novel β -indoloquinazoline analogues by altering the skeleton and introducing preferential side chains, evaluated their lipid-lowering activity and summarized the structure-activity relationships. In combination with an evaluation of the lipid-lowering efficacies, AMP-dependent activated protein kinase (AMPK) activating ability and liver microsomal stability, compound 23 (named as IQZ23) was selected for further studies. IQZ23 exerted a high efficacy in decreasing the triglyceride level (EC 50 = 0.033 μM) in 3T3-L1 adipocytes. Mechanistic studies revealed the lipid-lowering activity of IQZ23 was dependent on the AMPK pathway by modulating ATP synthase activity. This activation was accompanied by mitochondrial biogenesis and oxidation capacity increased, and insulin sensitivity enhanced in pertinent cell models by various interventions. Correspondingly, IQZ23 (20 mg/kg, i.p.) treatment significantly reversed high fat and cholesterol diet (HFC)- induced body weight increases and accompanying clinical symptoms of obesity in mice but without indicative toxicity. These results indicate that IQZ23 could be a useful candidate for the treatment of obesity and related metabolic disorders. Image 1 • 40 novel novel β -indoloquinazoline analogues were designed and synthesized. • The lipid-lowering activity was evaluated based on 3T3-L1 adipocyte model. • Compound IQZ23 shows a good drug-like properties and effectiveness on obesity mice. • Compound IQZ23 activates AMPK pathway by modulating ATP synthase activity. [ABSTRACT FROM AUTHOR]