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1.
J Org Chem ; 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31599586

RESUMO

We reported herein an unexpected cinchona alkaloid-derived squaramide-catalyzed asymmetric two-component Ugi-type reaction of α-aryl-substituted isocyanoacetates with C,N-cyclic azomethine imines, which provides concise access to optically active C1-oxazole-substituted tetrahydroisoquinolines in good yields (86-93%) and high enantioselectivities (up to 98% enantiomeric excess) under mild conditions.

2.
Nat Commun ; 10(1): 4285, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31537803

RESUMO

The preparation of fluorescent discrete supramolecular coordination complexes (SCCs) has attracted considerable attention within the fields of supramolecular chemistry, materials science, and biological sciences. However, many challenges remain. For instance, fluorescence quenching often occurs due to the heavy-atom effect arising from the Pt(II)-based building block in Pt-based SCCs. Moreover, relatively few methods exist for tuning of the emission wavelength of discrete SCCs. Thus, it is still challenging to construct discrete SCCs with high fluorescence quantum yields and tunable fluorescence wavelengths. Here we report nine organoplatinum fluorescent metallacycles that exhibit high fluorescence quantum yields and tunable fluorescence wavelengths through simple regulation of their photoinduced electron transfer (PET) and intramolecular charge transfer (ICT) properties. Moreover, 3D fluorescent films and fluorescent inks for inkjet printing were fabricated using these metallacycles. This work provides a strategy to solve the fluorescence quenching problem arising from the heavy-atom effect of Pt(II), and offers an alternative approach to tune the emission wavelengths of discrete SCCs in the same solvent.

3.
Int J Biol Macromol ; 140: 1175-1182, 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31465799

RESUMO

Traditional superhydrophobic cotton fabrics (SCFs) for oil/water separation were usually fabricated by surface coating with inorganic nanoparticles combined with nonrenewable and nonbiodegradable or even toxic fossil-based chemicals, which would lead to secondary environmental pollution after their lifetime. In this study, we report robust, nanoparticle-free, fluorine-free SFC, which was prepared by acid etching followed by surface coating with epoxidized soybean oil resin (CESO) and subsequent modification with stearic acid (STA). No toxic compound and no nanoparticle were included within the SCF and all the raw materials including cotton fabric, CESO and STA are biodegradable and derived from biological resources. The SCF showed excellent mechanical stability and chemical/environmental resistances. The superhydrophobicity of the SFC survived from mechanical abrasion, tape peeling, ultrasonication, solvent erosion and low/high temperature exposure. The SCF also exhibited good acid/alkali resistance with contact angle over 150° toward different pH water droplets. Moreover, the SCF could efficiently separate oil/water mixtures with efficiency above 97.9% and the superhydrophobicity remained after reusing for at least 10 times. The fully biological-derived SCF with excellent mechanical and chemical resistances exhibit great potential for separation of oil/water mixtures.

4.
Angew Chem Int Ed Engl ; 58(25): 8556-8560, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31046184

RESUMO

A new TiIII -mediated reductive epoxide-opening/ Beckwith-Dowd rearrangement process efficiently assembles the bicyclo[3.2.1]octane framework of highly oxidized grayanane diterpenoids. By incorporation of a Cu(tbs)2 -catalyzed (tbs=N-tert-butylsalicylaldiminato) intramolecular cyclopropanation, a diastereoselective oxidative dearomatization-induced Diels-Alder cycloaddition and a MeReO3 -catalyzed Rubottom oxidation, this approach has enabled the first total syntheses of rhodomolleins XX and XXII in 23 and 22 steps, respectively.

5.
Chemistry ; 25(9): 2189-2194, 2019 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-30548680

RESUMO

A new macrobicyclic molecule (BC-DAP5), consisting of a diaminopillar[5]arene cavity and a fused ring, was successfully constructed using a Grubbs metathesis reaction. Further studies indicated that BC-DAP5 possessed a unique molecular behavior, showing a response to acid/base stimuli. In BC-DAP5, protons (acid) acted as a lock, locking the fused ring out of the cavity (pillar[5]arene), and a base served as the key, making the fused ring switch in or out freely. Reversible control of the molecular behavior was achieved simply by adding acid and base alternately.

6.
Org Biomol Chem ; 17(3): 639-645, 2019 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-30575842

RESUMO

An efficient organocatalytic asymmetric tandem conjugate addition-protonation of α-substituted isocyanoacetates to 2-chloroacrylonitrile catalyzed by dihydroquinine-derived thiourea has been investigated, affording the corresponding adducts with two non-adjacent tertiary-quaternary stereocenters in excellent yields (up to 99%) along with good to excellent diastereo- and enantioselectivities (up to 20 : 1 dr, up to 95% ee) under mild conditions. The adduct can also be transformed into chiral γ-lactam by synthetic transformations.

7.
Eur J Pharmacol ; 834: 30-35, 2018 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-30012501

RESUMO

Inhibition of excessive osteoclast differentiation and activity is a valid approach for the treatment of osteoporosis. T63 is a small-molecule compound identified from a high throughput screening based on RUNX2 transcriptional activity, and has been reported to stimulate osteoblast formation. However, whether the compound has any effect on osteoclast differentiation remains unknown. Here, we examined the in vitro effect of T63 on osteoclastogenesis. T63 was found to inhibit the number of TRAP-positive cells in an osteoblast-osteoclast co-culture system, and inhibited Rankl expression in the preosteoblast MC3T3-E1 cells. The compound also directly suppressed RANKL-induced osteoclast differentiation in both dose- and time-dependent manner, as evidenced by the decrease of TRAP activity, F-actin formation and osteoclastogenesis-related genes expression in RAW264.7 cells. Moreover, pretreatment with T63 markedly decreased the activation of mitogen-activated protein kinases and Akt, both of which are positively involved in the regulation of osteoclastogenesis. Collectively, our findings suggest T63 has a protective effect against bone loss by inhibiting bone resorption. Its regulatory effect on bone metabolism makes the compound a more promising candidate for the potential application in the treatment of osteoporosis.

8.
Org Biomol Chem ; 16(25): 4641-4649, 2018 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-29901066

RESUMO

We have developed an efficient diastereo- and enantioselective Mannich/cyclization cascade reaction of α-substituted isocyanoacetates with 4-aryl-3-carbonyl-1,2,5-thiadiazole-1,1-dioxide type cyclic sulfamide ketimines cooperatively catalyzed by cinchona alkaloid-derived squaramide and AgOAc. The corresponding optically active 2,3,3a,4-tetrahydroimidazo[1,5-b][1,2,5]thiadiazole-1,1-dioxide derivatives were obtained in excellent yields (up to 99%) and good to excellent stereoselectivities (up to >20 : 1 dr, up to 94% ee).

9.
Dalton Trans ; 47(15): 5144-5148, 2018 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-29557473

RESUMO

A supramolecular organic framework, P5-bpy-SOF, made of perhydroxyl-pillar[5]arene (P5) and 4,4-bipyridine (bpy) and prepared by using a co-crystallization approach, showed a different hydrogen bonding pattern and a 3D molecular arrangement from that in the perhydroxyl-pillar[5]arene-based supramolecular organic framework (P5-SOF). TGA analyses, powder X-ray diffraction and gas absorption study confirmed P5-bpy-SOF's structural stability, permanent porosity, and, especially, selectivity of absorption of CO2 over N2.

10.
Org Biomol Chem ; 16(12): 2186, 2018 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-29512673

RESUMO

Correction for 'Guest-regulated chirality switching of planar chiral pseudo[1]catenanes' by Ya-Fen Yang et al., Org. Biomol. Chem., 2018, DOI: 10.1039/c8ob00156a.

11.
Org Biomol Chem ; 16(12): 2028-2032, 2018 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-29460948

RESUMO

pseudo[1]Catenane 3 is in a self-included conformation in chloroform, but in dichloromethane, it exists in an equilibrium between the self-included conformational state and a de-threading one. The planar chirality inversion of 3 can be triggered by the host-guest complexation of 3 with adiponitrile G, but the extent of such chiral switching depends on the length of self-included bis(pyrazin-2-yloxy)alkane chains in 3 - longer chains are more favored than shorter ones in the inversion.

12.
Inorg Chem ; 57(7): 3516-3520, 2018 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-29251490

RESUMO

A new discrete supramolecular metallacage functionalized with an alkynylplatinum(ll) 2,6-bis(benzimidazole-2'-yl)-pyridine (bzimpy) moiety has been successfully constructed via coordination-driven self-assembly. A study on the hierarchical self-assembly behavior of the obtained metallacage revealed that it displayed a solvent-induced emission switch accompanied by enhancement of the emission intensity as a result of the change in intermolecular Pt···Pt and π-π interactions. More interestingly, the metallacage has been found to spontaneously self-assemble into a transparent metallogel at room temperature without a heating-cooling process.

13.
Nat Commun ; 8(1): 1619, 2017 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-29158496

RESUMO

Optically active spirocyclic compounds play an important role in drug discovery, and new synthetic strategies for the efficient generation of spiro stereocenters are in much demand. Here we report a catalytic enantioselective cycloaddition using spirocyclic donor-acceptor cyclopropanes as a promising approach for the generation of spiro stereocenters. A diastereo- and enantioselective [3 + 3] cycloaddition of spirocyclopropyl oxindoles with both aldonitrones and ketonitrones is developed. The key to reaction development is the activation of spirocyclopropyl oxindoles by a suitable electron-withdrawing N-protecting group. This activation approach offers the promise of a general solution to enable spirocyclopropyl oxindoles as synthons for catalytic enantioselective synthesis of spirocyclic oxindoles featuring a C3 spiro stereocenter, a prominent structural motif in drugs and pharmaceutically active compounds. This protocol also constitutes the catalytic enantioselective reaction using unactivated achiral ketonitrones to construct tetrasubstituted carbon stereocenters.

14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 25(5): 1518-1523, 2017 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-29070136

RESUMO

OBJECTIVE: To explore the factors which may have influences on hematopoietic reconstitution of the auto-peripheral blood stem cell transplantation(auto-PBHSCT). METHODS: The successful rate, the time of hematopoietic reconstitution and implantation status at 28 days after transplantation of 177 patients received auto-PBSCT were retropectively analyzed, in order to explore the factors which may have influences on hematopoietic reconstitution. RESULTS: The median time of neutrophil recovery was 12 days (8-21 days), implantation rate was 98.9%, all patients' neutrophil were recovered in 28 days. The median time of platelet recovery was 17 days (7-420 days), implantation rate was 95.5%, the cumulative incidence of platelet recovery at day 28 was 80.8%. Univariate analysis showed that the CD34+ cell number and the use of TPO had effect on neutrophils recovery time; the disease kinds, conditioning regimen and the infused CD34+ cell number had influence on platelets recovery time. Multivariate analysis showed that the CD34+ cell number was the independent influencing factor of neutrophils reconstitution time; the disease kinds, the CD34+ cell number were the independent influencing factors of platelet reconstitution time. Disease kinds and the CD34+ cell number were the independent influencing factors of hematopoietic reconstitution status of 28 days after transplantation. CONCLUSION: In auto-PBHSCT patients, disease kinds, conditioning regimen, the infused CD34+ cell number and the use of TPO have been confirmed to be independent influencing factors on hematopoietic reconstitution.


Assuntos
Transplante de Células-Tronco de Sangue Periférico , Antígenos CD34 , Plaquetas , Contagem de Células , Glicosídeos , Transplante de Células-Tronco Hematopoéticas , Humanos , Neutrófilos , Pregnanos
15.
Yi Chuan ; 39(10): 897-907, 2017 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-29070485

RESUMO

Wnt signaling pathway plays important roles in the development and homeostasis of multicellular organisms. Through their bindings with the Frizzled receptors, the Wnt ligands regulate a wide range of developmental processes, such as axis patterning, cell division, and cell fate specification. Wnt signaling plays vital roles in the development of inner ear of the mouse. In the early stages of inner ear development, Wnt signaling specifies the size of the placode and the formation of the otic vesicle. In later stages, Wnt signaling mediates hair cell specification and orients the stereociliary bundles in a uniform direction. In this review, we summarize the current knowledge on the roles of Wnt signaling in hair cell differentiation and regeneration, which may provide references and insights for investigators in the field.


Assuntos
Células Ciliadas Auditivas/citologia , Regeneração , Via de Sinalização Wnt/fisiologia , Animais , Diferenciação Celular , Células Ciliadas Auditivas/fisiologia , Humanos , Trombospondinas/fisiologia
16.
Sci Rep ; 7(1): 10397, 2017 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-28871136

RESUMO

Osteoporosis results from the imbalance between bone resorption and bone formation, and restoring the normal balance of bone remodeling is highly desirable for identification of better treatment. In this study, using a cell-based high-throughput screening model representing Runt-related transcription factor 2 (RUNX2) transcriptional activity, we identified a novel small-molecular-weight compound, T63, as an efficient up-regulator of osteogenesis. T63 increased the alkaline phosphatase (ALPL) activity and mineralization as well as gene expression of Alpl and other osteogenic marker genes in mouse osteoblasts and mesenchymal stem cell-like cells. Upon induction of osteoblast differentiation, T63 inhibited adipogenic differentiation in the pluripotent mesenchymal cells. Consistently, T63 up-regulated RUNX2 mRNA and protein levels, and knockdown of RUNX2 reduced the osteogenic role of T63. Mechanistically, T63 activated both BMPs and WNT/ß-catenin signaling pathways. Inhibition of either signaling pathway with specific inhibitor suppressed T63-induced RUNX2 expression and the osteogenic phenotypes. Moreover, T63 markedly protected against bone mass loss in the ovariectomized and dexamethasone treated rat osteoporosis model. Collectively, our data demonstrate that T63 could be a promising drug candidate and deserves further development for potential therapeutics in osteoporosis.

17.
Angew Chem Int Ed Engl ; 56(46): 14438-14442, 2017 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-28961361

RESUMO

By simple ligand exchange of the cationic transition-metal complexes [(Cp*)M(acetone)3 ](OTf)2 (Cp*=pentamethylcyclopentadienyl and M=Ir or Rh) with pillar[5]arene, mono- and polynuclear pillar[5]arenes, a new class of metalated host molecules, is prepared. Single-crystal X-ray analysis shows that the charged transition-metal cations are directly bound to the outer π-surface of aromatic rings of pillar[5]arene. One of the triflate anions is deeply embedded within the cavity of the trinuclear pillar[5]arenes, which is different to the host-guest behavior of most pillar[5]arenes. DFT calculation of the electrostatic potential revealed that the metalated pillar[5]arenes featured an electron-deficient cavity due to the presence of the electron-withdrawing transition metals, thus allowing encapsulation of electron-rich guests mainly driven by anion-π interactions.

18.
Biochem Biophys Res Commun ; 488(1): 15-21, 2017 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-28465233

RESUMO

Aesculin (AES), a coumarin compound derived from Aesculus hippocasanum L, is reported to exert protective role against inflammatory diseases, gastric disease and cancer. However, direct effect of AES in bone metabolism is deficient. In this study, we examined the effects of AES on osteoclast (OC) differentiation in receptor activator of NF-κB ligand (RANKL)-induced RAW264.7 cells. AES inhibits the OC differentiation in both dose- and time-dependent manner within non-toxic concentrations, as analyzed by Tartrate Resistant Acid Phosphatase (TRAP) staining. The actin ring formation manifesting OC function is also decreased by AES. Moreover, expressions of osteoclastogenesis related genes Trap, Atp6v0d2, Cathepsin K and Mmp-9 are decreased upon AES treatment. Mechanistically, AES attenuates the activation of MAPKs and NF-κB activity upon RANKL induction, thus leading to the reduction of Nfatc1 mRNA expression. Moreover, AES inhibits Rank expression, and RANK overexpression markedly decreases AES's effect on OC differentiation and NF-κB activity. Consistently, AES protects against bone mass loss in the ovariectomized and dexamethasone treated rat osteoporosis model. Taken together, our data demonstrate that AES can modulate bone metabolism by suppressing osteoclastogenesis and related transduction signals. AES therefore could be a promising agent for the treatment of osteoporosis.


Assuntos
Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Esculina/farmacologia , Osteogênese/efeitos dos fármacos , Ligante RANK/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Esculina/administração & dosagem , Esculina/química , Camundongos , Conformação Molecular , Ligante RANK/metabolismo , Células RAW 264.7 , Relação Estrutura-Atividade
19.
Cell Death Dis ; 7(11): e2486, 2016 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-27882937

RESUMO

Lidamycin (LDM) is a novel member of the enediyne antibiotics identified in China with potent antitumor activity. However, it remains unclear whether LDM has potential molecular targets that may affect its antitumor activity. Enhancer of zeste homolog 2 (EZH2) functions as a histone lysine methyltransferase and mediates trimethylation on histone 3 lysine 27 (H3K27me3). High EZH2 level is found to be positively correlated with the aggressiveness, metastasis and poor prognosis of cancer. Here, we aim to study the role of EZH2 in LDM-induced senescence, as well as in the cytotoxicity of LDM in human colon cancer cells. LDM is found to be relatively more potent in inhibiting the colon cancer cells harboring high EZH2 level and induces irreversible cellular senescence at IC50 dose range, as evidenced by senescence-associated ß-galactosidase staining, cell cycle arrest and molecular changes of senescence regulators including p21 in HCT116 and SW620 cells. More importantly, LDM is found to markedly inhibit EZH2 expression at both protein and mRNA levels upon the induction of p21 and cellular senescence. LDM also selectively inhibits EZH2 expression as compared with other histone lysine methyltransferases. Knockdown of p21 with siRNAs abolishes LDM-induced senescence, whereas EZH2 knockdown markedly increases p21 expression and causes senescent phenotype. Enrichment of both EZH2 and H3K27me3 levels in the p21 promoter region is reduced by LDM. Moreover, EZH2 overexpression reduces cellular senescence, p21 expression and DNA damage response upon LDM exposure. LDM also demonstrates potent antitumor efficacy in xenografted animal models. Collectively, our work provides first demonstration that EZH2 may mediate, at least partially, the senescence-inducing effects of LDM by regulating p21 expression and DNA damage effect. Thus, EZH2 may serve as a potential target and biomarker to indicate the clinical efficacy of the potent enediyne antitumor drug.


Assuntos
Aminoglicosídeos/farmacologia , Senescência Celular/efeitos dos fármacos , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Inibidor de Quinase Dependente de Ciclina p21/genética , Enedi-Inos/farmacologia , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Antineoplásicos/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Dano ao DNA , Relação Dose-Resposta a Droga , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Células HCT116 , Células HT29 , Humanos , Concentração Inibidora 50 , Gradação de Tumores , Regiões Promotoras Genéticas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 24(4): 1155-62, 2016 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-27531792

RESUMO

OBJECTIVE: To establish the S1PR5 gene knockout mouse model by using CRISPR/Cas9 gene editing technique so as to provide the tool for studying the regulating role of sphingosine-1-phosphate receptor 5 (S1PR5) in allogeneic hematopoietic stem cell transplantation. METHODS: Single guide RNA (sgRNA) plasmids against the exon 3 of S1PR5 were designed and constructed. Then the sgRNA and hCas9 were transcribed by T7 RNA polymerase in vitro. Cas9 mRNA and sgRNA were mixed and microinjected into fertilized eggs of C57BL/6 mice. T7E1 digestion and gene sequencing were used to detect the mutations of S1PR5. Quantitative PCR (qPCR) and Western blot were used to detect the expression of S1PR5. RESULTS: Finally 2 kinds of F2 generation of homozygous S1PR5 deficent mice (S1PR5-170/-170 mice and S1PR5-215/-215 mice) were gained, and in these 2 model mice the S1PR5 did not express at mRNA and protein levels. CONCLUSION: A mouse model with S1PR5 dificiency has been successfully established, which shall lay a foundation for future investigation of S1PR5.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Animais , Técnicas de Inativação de Genes , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microinjeções , Mutação , Plasmídeos , RNA Guia , Receptores de Lisoesfingolipídeo , Zigoto
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