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1.
Cell ; 180(1): 176-187.e19, 2020 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-31923394

RESUMO

In response to biotic stress, plants produce suites of highly modified fatty acids that bear unusual chemical functionalities. Despite their chemical complexity and proposed roles in pathogen defense, little is known about the biosynthesis of decorated fatty acids in plants. Falcarindiol is a prototypical acetylenic lipid present in carrot, tomato, and celery that inhibits growth of fungi and human cancer cell lines. Using a combination of untargeted metabolomics and RNA sequencing, we discovered a biosynthetic gene cluster in tomato (Solanum lycopersicum) required for falcarindiol production. By reconstituting initial biosynthetic steps in a heterologous host and generating transgenic pathway mutants in tomato, we demonstrate a direct role of the cluster in falcarindiol biosynthesis and resistance to fungal and bacterial pathogens in tomato leaves. This work reveals a mechanism by which plants sculpt their lipid pool in response to pathogens and provides critical insight into the complex biochemistry of alkynyl lipid production.


Assuntos
Di-Inos/metabolismo , Ácidos Graxos/biossíntese , Álcoois Graxos/metabolismo , Lycopersicon esculentum/genética , Resistência à Doença/genética , Di-Inos/química , Ácidos Graxos/metabolismo , Álcoois Graxos/química , Regulação da Expressão Gênica de Plantas/genética , Metabolômica , Família Multigênica/genética , Doenças das Plantas/microbiologia , Folhas de Planta/metabolismo , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Estresse Fisiológico/genética
2.
Biomolecules ; 9(12)2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31861234

RESUMO

Polyacetylenic compounds isolated from Panax species are comprised of non-polar C17 compounds, exhibiting anti-inflammatory, antitumor, and antifungal activities. Panaxynol represents the major component of the essential oils of ginseng. We investigated whether panaxynol isolated from Panax vietnamensis (Vietnamese ginseng, VG) could prevent cisplatin-induced renal damage induced in vitro and in vivo. Cisplatin-induced apoptotic cell death was observed by staining with annexin V conjugated with Alexa Fluor 488, and western blotting evaluated the molecular mechanism. Panaxynol at concentrations above 0.25 µM prevented cisplatin-induced LLC-PK1 porcine renal proximal tubular cell death. LLC-PK1 cells treated with cisplatin demonstrated an increase in apoptotic cell death, whereas pretreatment with 2 and 4 µM panaxynol decreased this effect. Cisplatin demonstrated a marked increase in the phosphorylation of c-Jun N-terminal kinase (JNK), P38, and cleaved caspase-3. However, pretreatment with 2 and 4 µM panaxynol reversed the upregulated phosphorylation of JNK, P38, and the expression of cleaved caspase-3. We confirmed that the protective effect of panaxynol isolated from P. vietnamensis in LLC-PK1 cells was at least partially mediated by reducing the cisplatin-induced apoptotic damage. In the animal study, panaxynol treatment ameliorated body weight loss and blood renal function markers and downregulated the mRNA expression of inflammatory mediators.


Assuntos
Lesão Renal Aguda/tratamento farmacológico , Cisplatino/farmacologia , Di-Inos/farmacologia , Álcoois Graxos/farmacologia , Túbulos Renais Proximais/efeitos dos fármacos , Panax/química , Substâncias Protetoras/farmacologia , Lesão Renal Aguda/induzido quimicamente , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Nitrogênio da Ureia Sanguínea , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Creatinina/sangue , Di-Inos/química , Di-Inos/isolamento & purificação , Álcoois Graxos/química , Álcoois Graxos/isolamento & purificação , Túbulos Renais Proximais/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Substâncias Protetoras/química , Substâncias Protetoras/isolamento & purificação , Suínos
3.
J Pept Sci ; 25(7): e3194, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31215108

RESUMO

Short alphahelical peptide sequences were stabilized through Glaser-Hay couplings of propargylated l- and/or d-serine residues at positions i and i+7. NMR analysis confirmed a full stabilization of the helical structure when a d-Ser (i), l-Ser (i+7) combination was applied. In case two l-Ser residues were involved in the cyclization, the helical conformation is disrupted outside the peptide's macrocycle.


Assuntos
Di-Inos/química , Peptídeos/química , Sequência de Aminoácidos , Conformação Proteica em alfa-Hélice , Estabilidade Proteica , Estereoisomerismo
4.
Z Naturforsch C J Biosci ; 74(5-6): 145-150, 2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-30721147

RESUMO

Phytochemical investigation of Polyscias guilfoylei leaves extract (PGE) led to the isolation of nine compounds, that is, ent-labda-8(17),13-diene-15,18-diol (1), stigmasterol (2), spinasterol (3), N-(1,3-dihydroxyoctadecan-2-yl) palmitamide (4), panaxydiol (5), 3-O-ß-d-glucopyranosylstigmasta-5,22-diene-3-ß-ol (6), (8Z)-2-(2 hydroxypentacosanoylamino) octadeca-8-ene-1,3,4-triol (7), 4-hydroxybenzoic acid (8), and tamarixetin 3,7-di-O-α-L-rhamnopyranoside (9). Compound 4 is reported in this study for the first time in nature whereas compound 9 is reported for the second time. Structural elucidation of the compounds was carried out using Nuclear Magnetic Resonance and Electrospray Ionization coupled with Mass Spectrometry spectroscopic analyses. PGE and compounds 4 and 9 exhibited weak cytotoxicity against both MCF-7 and HCT-116 cell lines using 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide assay. The antimicrobial activity of PGE and compounds 4 and 9 was evaluated using the agar diffusion method. Escherichia coli was the most susceptible Gram-negative bacteria toward PGE with a minimum inhibitory concentration value of 9.76 µg/mL, whereas compounds 4 and 9 did not show any antimicrobial activity. Compound 4 exhibited promising inhibition of histamine release using U937 human monocytes with an IC50 value of 38.65 µg/mL.


Assuntos
Anti-Infecciosos/química , Antineoplásicos/química , Araliaceae/química , Antagonistas dos Receptores Histamínicos/química , Extratos Vegetais/química , Anti-Infecciosos/farmacologia , Antineoplásicos/farmacologia , Dissacarídeos/química , Dissacarídeos/farmacologia , Di-Inos/química , Di-Inos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Células HCT116 , Antagonistas dos Receptores Histamínicos/farmacologia , Humanos , Células MCF-7 , Extratos Vegetais/farmacologia , Folhas de Planta/química , Quercetina/análogos & derivados , Quercetina/química , Quercetina/farmacologia , Estigmasterol/análogos & derivados , Estigmasterol/farmacologia
5.
ACS Comb Sci ; 21(4): 316-322, 2019 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-30673274

RESUMO

We present the application of a Glaser-Hay diyne coupling for the synthesis of conformationally constrained Nα-amino acid amides with different diyne ring sizes. Twelve-membered rings were the smallest rings that could be prepared by this approach. We observed the formation of triethylammonium adducts in the cases of smaller (10- and 11-membered) rings. Calculation of the conformational barriers for the cyclization reactions of various ring sizes demonstrated that the formation of amino acid-derived smaller rings by this reaction is thermodynamically unfavorable.


Assuntos
Amidas/síntese química , Aminoácidos/química , Di-Inos/química , Alquinos/química , Aminas/química , Catálise , Ciclização , Modelos Moleculares , Conformação Molecular , Técnicas de Síntese em Fase Sólida/métodos , Termodinâmica
6.
Oxid Med Cell Longev ; 2018: 3153527, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30420908

RESUMO

Nuclear factor- (erythroid-derived 2) like 2 (Nrf2) is a transcription factor that regulates the expression of a battery of antioxidant, anti-inflammatory, and cytoprotective enzymes including heme oxygenase-1 (Hmox1, Ho-1) and NADPH:quinone oxidoreductase-1 (Nqo1). The isothiocyanate sulforaphane (SF) is widely understood to be the most effective natural activator of the Nrf2 pathway. Falcarinol (FA) is a lesser studied natural compound abundant in medicinal plants as well as dietary plants from the Apiaceae family such as carrot. We evaluated the protective effects of FA and SF (5 mg/kg twice per day in CB57BL/6 mice) pretreatment for one week against acute intestinal and systemic inflammation. The phytochemical pretreatment effectively reduced the magnitude of intestinal proinflammatory gene expression (IL-6, Tnfα/Tnfαr, Infγ, STAT3, and IL-10/IL-10r) with FA showing more potency than SF. FA was also more effective in upregulating Ho-1 at mRNA and protein levels in both the mouse liver and the intestine. FA but not SF attenuated plasma chemokine eotaxin and white blood cell growth factor GM-CSF, which are involved in the recruitment and stabilization of first-responder immune cells. Phytochemicals generally did not attenuate plasma proinflammatory cytokines. Plasma and intestinal lipid peroxidation was also not significantly changed 4 h after LPS injection; however, FA did reduce basal lipid peroxidation in the mesentery. Both phytochemical pretreatments protected against LPS-induced reduction in intestinal barrier integrity, but FA additionally reduced inflammatory cell infiltration even below negative control.


Assuntos
Dieta , Di-Inos/uso terapêutico , Álcoois Graxos/uso terapêutico , Heme Oxigenase-1/biossíntese , Inflamação/tratamento farmacológico , Inflamação/enzimologia , Intestinos/patologia , Isotiocianatos/uso terapêutico , Animais , Citocinas/sangue , Di-Inos/química , Di-Inos/farmacologia , Indução Enzimática/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Álcoois Graxos/química , Álcoois Graxos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/genética , Inflamação/patologia , Isotiocianatos/química , Isotiocianatos/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Transdução de Sinais/efeitos dos fármacos
7.
Chembiochem ; 19(21): 2293-2299, 2018 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-30136342

RESUMO

A chiral amino alcohol based ligand was found to promote the highly enantioselective addition of terminal conjugated diynes to aromatic and aliphatic aldehydes. The combination of easily available C2 -symmetric (R)- and (S)-BINOL with Ti(OiPr)4 , Zn powder, and EtI was also found to catalyze the asymmetric addition of 1,3-diynes to aldehydes under mild reaction conditions, and thus, both enantiomers of the chiral conjugated diynols could be prepared with high enantioselectivities. The resulting optically active conjugated diynols were found to have potential anticancer activities with significant differences against HepG2 and HeLa cancer cells, and remarkable enantioselective cytotoxicity was observed for the first time.


Assuntos
Aldeídos/química , Amino Álcoois/química , Antineoplásicos/química , Di-Inos/química , Aldeídos/síntese química , Aldeídos/farmacologia , Amino Álcoois/síntese química , Amino Álcoois/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Catálise , Di-Inos/síntese química , Di-Inos/farmacologia , Células HeLa , Células Hep G2 , Humanos , Ligantes , Naftóis/síntese química , Naftóis/química , Naftóis/farmacologia , Neoplasias/tratamento farmacológico , Estereoisomerismo , Titânio/química , Zinco/química
8.
Mini Rev Med Chem ; 18(12): 1064-1070, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29468966

RESUMO

BACKGROUND: The 3,4-diyne substituted isocoumarins have been designed, synthesized and explored as potential anti-proliferative agents. METHOD: Ultrasound assisted synthesis of these compounds was carried out by using a three-step method involving (i) Pd/C-Cu catalyzed cross-coupling between the methyl 2-iodobenzoate and buta- 1,3-diynylbenzene followed by (ii) I2-mediated electrophilic cyclization of the resultant 2-(alk-1- ynyl)benzoate ester and (iii) subsequent alkynylation of 4-iodo-3-(phenylethynyl)-isocoumarin under Pd/C-Cu catalysis. CONCLUSION: The synthesized compounds showed promising growth inhibition when tested against MDA-MB 231 and K562 cancer cell lines.


Assuntos
Antineoplásicos/farmacologia , Citotoxinas/farmacologia , Di-Inos/farmacologia , Isocumarinas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citotoxinas/síntese química , Citotoxinas/química , Di-Inos/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Isocumarinas/síntese química , Isocumarinas/química , Relação Estrutura-Atividade
9.
Chem Commun (Camb) ; 54(16): 2008-2011, 2018 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-29411793

RESUMO

Classical synthetic approaches to highly unsaturated polyene/yne natural products rely on iterative cross-coupling of linear fragments. Herein, we present an expeditious and unified approach to the unsaturated backbone of polyacetylenes via domino cuprate addition/4π-electrocyclic ring opening of a stereodefined cyclobutene intermediate. This sets the stage for a detailed biological assessment of the role of Virol A and Cicutoxin as inhibitors of GABA induced chloride currents, providing further insight into the interaction of these highly potent toxins towards the GABAA receptor, including the structure-activity relationship of the derivatives.


Assuntos
Produtos Biológicos/farmacologia , Di-Inos/farmacologia , Álcoois Graxos/farmacologia , Poli-Inos/farmacologia , Receptores de GABA-A/metabolismo , Produtos Biológicos/síntese química , Produtos Biológicos/química , Di-Inos/síntese química , Di-Inos/química , Álcoois Graxos/síntese química , Álcoois Graxos/química , Humanos , Estrutura Molecular , Poli-Inos/química , Isoformas de Proteínas/efeitos dos fármacos , Isoformas de Proteínas/metabolismo , Receptores de GABA-A/química , Água/química
10.
Planta Med ; 84(11): 806-812, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29301145

RESUMO

Three diynes, octadec-17-ene-9,11-diynoate ethyl (1: ), 8-hydroxy-octadeca-13,17-diene-9,11-diynoate ethyl (2: ), and 8-hydroxy-octadec-13-ene-9,11-diynoate ethyl (3: ), were isolated from Ongokea gore seed oil. The structure assignment of these three compounds was based according to chemical and spectroscopic data. They were screened against Plasmodium falciparum, the parasite that causes malaria. In vitro micro-test (Mark III, supported by the World Health Organization) was developed to assess the response of P. falciparum to the isolated three compounds, and statistical analysis were performed for determination of the concentration that inhibits 50% of the parasite maturation (IC50). Two of the three diynes (2: and 3: ) showed a very effective in vitro antimalarial activity with an IC50 of 4.5 and 1.7 µM, respectively. Compound 3: exhibited better activity than quinine (IC50 1.9 µM), the drug reference, while compound 1: had no antimalarial activity (IC50 > 125 µM). In the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cytotoxicity screening, all compounds showed no toxicity (mean IC50 of 90 µM for each compound).


Assuntos
Antimaláricos/farmacologia , Di-Inos/farmacologia , Embriófitas/química , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Antimaláricos/química , Antimaláricos/isolamento & purificação , Pré-Escolar , Di-Inos/química , Di-Inos/isolamento & purificação , Humanos , Masculino , Óleos Vegetais/química , Sementes/química
11.
Macromol Rapid Commun ; 39(4)2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29171703

RESUMO

This study reports the first Co2 (CO)8 -catalyzed [2+2+2] polycyclotrimerization by the transformation of internal ethynyl groups of aromatic diyne monomers. The reaction yields polycyclotrimers of polyphenylene-type with either hyperbranched or partly crosslinked architecture. The homopolycyclotrimerization of the monomers with two ethynyl groups per one molecule, namely 1,4-bis(phenylethynyl)benzene, 4,4'-bis(phenylethynyl)biphenyl, and 4-(phenylethynyl)phenylacetylene, gives partly crosslinked, insoluble polyphenylenes. The soluble, hyperbranched polyphenylenes are generated via copolycyclotrimerization of 1,4-bis(phenylethynyl)benzene with 1,2-diphenylacetylene (average number of ethynyl groups per monomer molecule < 2). This one-step polycyclotrimerization path to hyperbranched or partly crosslinked polyphenylenes is an alternative to the synthesis of these polymers by Diels-Alder transformation of substituted cyclopentadienones. All polyphenylenes prepared exhibit photoluminescence with emission maxima ranging from 381 to 495 nm. Polyphenylenes with a less compact packing of segments are microporous (specific surface area up to 159 m2 g-1 ), which is particularly important in the case of soluble polyphenylenes because they can be potentially used to prepare microporous layers.


Assuntos
Di-Inos/química , Substâncias Luminescentes/química , Substâncias Macromoleculares/química , Polímeros/química , Catálise , Substâncias Luminescentes/síntese química , Substâncias Macromoleculares/síntese química , Estrutura Molecular , Polimerização , Porosidade
12.
Angew Chem Int Ed Engl ; 56(26): 7444-7448, 2017 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-28561942

RESUMO

In total and formal syntheses of dictyodendrins B, C, E, and F, the key step involved the direct construction of the pyrrolo[2,3-c]carbazole core by the gold-catalyzed annulation of a conjugated diyne with a pyrrole to form three bonds and two aromatic rings. The subsequent introduction of substituents at the C1 (Suzuki-Miyaura coupling), C2 (addition to an aldehyde), N3 (alkylation), and C5 positions (Ullman coupling) provided divergent access to dictyodendrins.


Assuntos
Carbazóis/síntese química , Di-Inos/química , Ouro/química , Pirróis/síntese química , Carbazóis/química , Catálise , Ciclização , Estrutura Molecular , Pirróis/química
13.
Molecules ; 22(1)2017 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-28075366

RESUMO

Despite significant advances in the last three decades towards high yielding syntheses of rotaxanes, the preparation of systems constructed from more than two components remains a challenge. Herein we build upon our previous report of an active template copper-catalyzed azide-alkyne cycloaddition (CuAAC) rotaxane synthesis with a diyne in which, following the formation of the first mechanical bond, the steric bulk of the macrocycle tempers the reactivity of the second alkyne unit. We have now extended this approach to the use of 1,3,5-triethynylbenzene in order to successively prepare [2]-, [3]- and [4]rotaxanes without the need for protecting group chemistry. Whilst the first two iterations proceeded in good yield, the steric shielding that affords this selectivity also significantly reduces the efficacy of the active template (AT)-CuAAC reaction of the third alkyne towards the preparation of [4]rotaxanes, resulting in severely diminished yields.


Assuntos
Reação de Cicloadição/métodos , Rotaxanos/síntese química , Alquinos/química , Azidas/química , Derivados de Benzeno/química , Catálise , Cobre/química , Cristalografia por Raios X , Di-Inos/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular
14.
Molecules ; 22(1)2017 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-28075414

RESUMO

Transition-metal-free synthesis of 4-pyrones via TfOH-promoted nucleophilic addition/cyclization of diynones and water has been developed. This transformation is simple, atom economical and environmentally benign, providing rapid and efficient access to substituted 4-pyrones.


Assuntos
Catálise , Di-Inos/síntese química , Pironas/síntese química , Ciclização , Di-Inos/química , Estrutura Molecular , Pironas/química , Estereoisomerismo , Água/química
15.
Molecules ; 21(10)2016 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-27669203

RESUMO

During a screening program for new agrochemicals from Chinese medicinal herbs, the ethanol extract of Notopterygium incisum rhizomes was found to possess strong nematicidal activity against the two species of nematodes, Bursaphelenchus xylophilus and Meloidogyne incognita. Based on bioactivity-guided fractionation, the four constituents were isolated from the ethanol extract and identified as columbianetin, falcarindiol, falcarinol, and isoimperatorin. Among the four isolated constituents, two acetylenic compounds, falcarindiol and falcarinol (2.20-12.60 µg/mL and 1.06-4.96 µg/mL, respectively) exhibited stronger nematicidal activity than two furanocoumarins, columbianetin, and isoimperatorin (21.83-103.44 µg/mL and 17.21-30.91 µg/mL, respectively) against the two species of nematodes, B. xylophilus and M. incognita. The four isolated constituents also displayed phototoxic activity against the nematodes. The results indicate that the ethanol extract of N. incisum and its four isolated constituents have potential for development into natural nematicides for control of plant-parasitic nematodes.


Assuntos
Apiaceae/química , Extratos Vegetais/farmacologia , Tylenchida/efeitos dos fármacos , Tylenchoidea/efeitos dos fármacos , Animais , Di-Inos/química , Medicamentos de Ervas Chinesas/farmacologia , Álcoois Graxos/química , Furocumarinas/química , Extratos Vegetais/química , Rizoma/química , Tylenchida/patogenicidade , Tylenchoidea/patogenicidade
16.
BMC Genomics ; 17(1): 621, 2016 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-27514659

RESUMO

BACKGROUND: The treatment of microbial infections is becoming increasingly challenging because of limited therapeutic options and the growing number of pathogenic strains that are resistant to current antibiotics. There is an urgent need to identify molecules with novel modes of action to facilitate the development of new and more effective therapeutic agents. The anti-mycobacterial activity of the C17 diyne natural products falcarinol and panaxydol has been described previously; however, their mode of action remains largely undetermined in microbes. Gene expression profiling was therefore used to determine the transcriptomic response of Mycobacterium smegmatis upon treatment with falcarinol and panaxydol to better characterize the mode of action of these C17 diynes. RESULTS: Our analyses identified 704 and 907 transcripts that were differentially expressed in M. smegmatis after treatment with falcarinol and panaxydol respectively. Principal component analysis suggested that the C17 diynes exhibit a mode of action that is distinct to commonly used antimycobacterial drugs. Functional enrichment analysis and pathway enrichment analysis revealed that cell processes such as ectoine biosynthesis and cyclopropane-fatty-acyl-phospholipid synthesis were responsive to falcarinol and panaxydol treatment at the transcriptome level in M. smegmatis. The modes of action of the two C17 diynes were also predicted through Prediction of Activity Spectra of Substances (PASS). Based upon convergence of these three independent analyses, we hypothesize that the C17 diynes inhibit fatty acid biosynthesis, specifically phospholipid synthesis, in mycobacteria. CONCLUSION: Based on transcriptomic responses, it is suggested that the C17 diynes act differently than other anti-mycobacterial compounds in M. smegmatis, and do so by inhibiting phospholipid biosynthesis.


Assuntos
Antituberculosos/farmacologia , Produtos Biológicos/farmacologia , Di-Inos/farmacologia , Ácidos Graxos/antagonistas & inibidores , Álcoois Graxos/farmacologia , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Mycobacterium smegmatis/efeitos dos fármacos , Diamino Aminoácidos/antagonistas & inibidores , Diamino Aminoácidos/biossíntese , Antituberculosos/química , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Produtos Biológicos/química , Di-Inos/química , Ácidos Graxos/biossíntese , Álcoois Graxos/química , Perfilação da Expressão Gênica , Ontologia Genética , Anotação de Sequência Molecular , Mycobacterium smegmatis/genética , Mycobacterium smegmatis/metabolismo , Fosfolipídeos/biossíntese , Análise de Componente Principal , RNA Bacteriano/antagonistas & inibidores , RNA Bacteriano/biossíntese , RNA Bacteriano/genética , Transcriptoma
17.
Nature ; 532(7600): 484-8, 2016 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-27088605

RESUMO

In the classic Diels-Alder [4 + 2] cycloaddition reaction, the overall degree of unsaturation (or oxidation state) of the 4π (diene) and 2π (dienophile) pairs of reactants dictates the oxidation state of the newly formed six-membered carbocycle. For example, in the classic Diels-Alder reaction, butadiene and ethylene combine to produce cyclohexene. More recent developments include variants in which the number of hydrogen atoms in the reactant pair and in the resulting product is reduced by, for example, four in the tetradehydro-Diels-Alder (TDDA) and by six in the hexadehydro-Diels-Alder (HDDA) reactions. Any oxidation state higher than tetradehydro (that is, lacking more than four hydrogens) leads to the production of a reactive intermediate that is more highly oxidized than benzene. This increases the power of the overall process substantially, because trapping of the reactive intermediate can be used to increase the structural complexity of the final product in a controllable and versatile manner. Here we report an unprecedented overall 4π + 2π cycloaddition reaction that generates a different, highly reactive intermediate known as an α,3-dehydrotoluene. This species is in the same oxidation state as a benzyne. Like benzynes, α,3-dehydrotoluenes can be captured by various trapping agents to produce structurally diverse products that are complementary to those arising from the HDDA process. We call this new cycloisomerization process a pentadehydro-Diels-Alder (PDDA) reaction-a nomenclature chosen for chemical taxonomic reasons rather than mechanistic ones. In addition to alkynes, nitriles (RC≡N), although non-participants in aza-HDDA reactions, readily function as the 2π component in PDDA cyclizations to produce, via trapping of the α,3-(5-aza)dehydrotoluene intermediates, pyridine-containing products.


Assuntos
Reação de Cicloadição , Hidrogênio/química , Tolueno/análogos & derivados , Benzeno/química , Ciclização , Di-Inos/química , Hidrogenação , Isomerismo , Nitrilos/química , Oxirredução , Piridinas/química , Terminologia como Assunto , Tolueno/síntese química , Tolueno/química
18.
Anal Chem ; 88(7): 3804-9, 2016 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-26974586

RESUMO

We report herein the fabrication of novel microarrays based on air-stable functional lipid monolayers over silicon using a combination of e-beam lithography and lift-off. We demonstrate these microarrays can be use as ultrasensitive platform for Kelvin probe force microscopy in sensing experiments. Specificity of the detection is given by the functional group grafted at the lipid headgroup. The arrays developed for the detection of ferric ions, Fe(3+), using a γ-pyrone derivative chelator, demonstrate subpicomolar limit of detection with high specificity. In addition, the technique takes advantage of the structure of the array with the silicon areas playing the role of reference for the measurement, and we determine critical pattern dimensions below which the probe size/shape impacts the measured results.


Assuntos
Ferro/análise , Membranas Artificiais , Análise em Microsséries/instrumentação , Di-Inos/química , Limite de Detecção , Fosfatidilcolinas/química , Pironas/química , Silício/química
19.
Macromol Rapid Commun ; 37(8): 685-90, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26924039

RESUMO

Diarylbutadiyne derivatives are ideal monomers for providing the π-electron-conjugated system of polydiacetylenes (PDAs). The geometrical parameters for diacetylene topochemical polymerization are known. However, control of the molecules under these parameters is yet to be addressed. This work shows that by simply tailoring diarylbutadiyne with amide side-chain substituents, the arrangement of the substituents and the resulting hydrogen bond framework allows formation of π-electron-conjugated PDA.


Assuntos
Polímeros/síntese química , Poli-Inos/síntese química , Amidas/química , Di-Inos/química , Elétrons , Ligação de Hidrogênio , Estrutura Molecular , Polímero Poliacetilênico , Polímeros/química , Poli-Inos/química
20.
Org Lett ; 18(5): 1162-5, 2016 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-26886865

RESUMO

The first total synthesis of the polyacetylene natural product atractylodemayne A is reported. Stereoselective construction of the conjugated 8(Z),10(E)-diene moiety was achieved through a tethered ring-closing metathesis approach, comprising a Ru-catalyzed RCM followed by a base-induced elimination. A Pd-catalyzed Cadiot-Chodkiewicz coupling was used for the synthesis of the diyne. Overall, atractylodemayne A was synthesized in nine steps for the longest linear sequence.


Assuntos
Produtos Biológicos/síntese química , Di-Inos/síntese química , Polienos/síntese química , Produtos Biológicos/química , Catálise , Ciclização , Di-Inos/química , Álcoois Graxos , Estrutura Molecular , Polienos/química , Estereoisomerismo
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