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1.
J Sep Sci ; 42(24): 3631-3639, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31651081

RESUMO

The interactive behavior of an amphipathic peptide with the Cu2+ , Ni2+ , and Zn2+ complexes of 1,4-bis(triazacyclonon-1-yl)butane), bis(tacn)but , immobilized onto Sepharose CL-4B, has been investigated. The effects of incubation time, as well as the incubation buffer pH and ionic strength, have been examined. The binding data have been interrogated using Langmuir, Langmuir-Freundlich, bi-Langmuir, and Temkin isothermal models and Scatchard plots. These results confirm that this amphipathic peptide binds with relatively high capacities to the immobilized Cu2+ - and Ni2+ -1,4-bis(triazacyclonon-1-yl)butane)-Sepharose CL-4B sorbents via at least two discrete sites. However, the corresponding immobilized Zn2+ -sorbent had low binding capacity. Moreover, the magnitude of the binding capacities of these sorbents was dependent on the pH and ionic strength of the incubation buffer. These results are relevant to the isolation of E. coli expressed recombinant proteins that incorporate this and related amphipathic peptide tags, containing two or more histidine residues, located at the N- or C-terminus of the recombinant protein, and the co-purification of low abundance host cell proteins of diverse structure, by immobilized metal ion affinity chromatographic methods.


Assuntos
Quelantes/química , Ciclobutanos/química , Compostos Organometálicos/química , Tensoativos/química , Zinco/química , Adsorção , Cromatografia de Afinidade , Ciclobutanos/síntese química , Histidina/química , Concentração de Íons de Hidrogênio , Ligantes , Metais Pesados/química , Compostos Organometálicos/síntese química , Peptídeos/química , Resinas Sintéticas/química , Cloreto de Sódio/química , Propriedades de Superfície
2.
Int J Mol Sci ; 20(18)2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31487921

RESUMO

Efficient and versatile synthetic methodologies are reported for the preparation of products that are suitable candidates to be used as surfactants, gelators for hydroxylic solvents or metal cation ligands, with potential use in several fields including biomedical applications. The common structural feature of all the synthesized products is the presence of a cis or trans-1,2- or cis-1,3-difunctionalized cyclobutane ring. In the two first cases, the key intermediates including enantiomerically pure 1,3-diamines and 1,3-amino alcohols have been prepared from ß-amino acid derivatives obtained, in turn, from a chiral half-ester. This compound is also precursor of γ-amino esters. Furthermore, two kind of polydentate ligands have also been synthesized from a symmetric 1,5-diamine obtained from norpinic acid, which was easily prepared from commercial verbenone.


Assuntos
Ciclobutanos/síntese química , Cátions/química , Géis/síntese química , Ligantes , Solventes/síntese química , Tensoativos/síntese química
3.
Molecules ; 24(18)2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31491981

RESUMO

The coupling of 2-bromo-3-benzoyloxycyclobutanone with purine under basic conditions produces two regioisomers consisting of the N-7 and N-9 alkylated products in equal amounts in their racemic forms. The distribution of the isomers is consistent with the charge delocalization between the N-7 and N-9 positions of the purinyl anion. The structural assignments and relative stereochemistry of each regioisomer were based on 1 and 2D NMR techniques. The relative stereochemistry of the C-2 and C-3 substituents in each regioisomer was the trans orientation consistent with steric factors in the coupling step. The N-9 regioisomer was reduced with sodium borohydride to give the all trans cyclobutanol as the major product in a stereoselective manner. The alcohol was debenzoylated with sodium methoxide in a transesterification step to give the nucleoside analogue. The regioisomeric pyrimidine nucleosides were prepared by Vorbrüggen coupling of the 3-hydroxymethylcyclobutanone triflate with either thymine or uracil followed by stereoselective hydride addition. Regiospecificity of the coupling at the N-1 position was observed and stereoselective reduction to the trans-disubstituted cyclobutanol structure assignments was based on NMR data.


Assuntos
Ciclobutanos/síntese química , Técnicas de Química Sintética , Ciclobutanos/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Purinas/química , Nucleosídeos de Pirimidina/química , Estereoisomerismo
4.
Acta Crystallogr C Struct Chem ; 75(Pt 8): 1091-1101, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31380792

RESUMO

A new set of differently hydrated barium and strontium squarates, namely poly[[triaqua(µ-1,2-dioxocyclobut-3-ene-1,2-diolato)barium] monohydrate], {[Ba(C4O4)(H2O)3]·H2O}n (1), poly[[diaqua(µ-1,2-dioxocyclobut-3-ene-1,2-diolato)strontium] monohydrate], {[Sr(C4O4)(H2O)2]·H2O}n (2), and poly[[triaqua(µ-1,2-dioxocyclobut-3-ene-1,2-diolato)barium/strontium(0.85/0.15)] monohydrate], {[Ba0.85Sr0.15(C4O4)(H2O)3]·H2O}n (3), is reported. The study of their crystal structures indicates that all the complexes crystallize in the triclinic space group P-1. Complexes 1 and 3 have a rare combination of squarate units coordinated through monodentate O atoms to two different metal atoms and through two bidentate O atoms to three different metal atoms. Furthermore, they have three coordinated water molecules to give a coordination number of nine. The squarate ligands in complex 2 exhibit two different coordination modes: (i) monodentate O atoms coordinated to four different Sr atoms and (ii) two monodentate O atoms coordinated to two different metal atoms with the other two O atoms bidentate to four different Sr atoms. All the compounds decompose to give the respective carbonates when heated to 800 °C, as evidenced by thermogravimetry/differential thermal analysis (TG-DTA), which are clusters of nanoparticles. Complexes 1 and 3 show additional endothermic peaks at 811 and 820 °C, respectively, indicating the phase transition of BaCO3 from an orthorhombic (α-Pmcn) to a trigonal phase (ß-R3m). All three complexes have significant DNA-binding constants, ranging from 2.45 × 104 to 9.41 × 104 M-1 against EB-CT (ethidium bromide-calf thymus) DNA and protein binding constants ranging from 1.1 × 105 to 8.6 × 105 with bovine serum albumin. The in vitro cytotoxicity of the complexes is indicated by the IC50 values, which range from 128.8 to 261.3 µg ml-1. Complex 3 shows better BSA binding, antioxidant activity against the DPPH radical and cytotoxicity than complexes 1 and 2.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Ciclobutanos/farmacologia , Depuradores de Radicais Livres/farmacologia , Substâncias Intercalantes/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/metabolismo , Bário/química , Bovinos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Complexos de Coordenação/metabolismo , Cristalografia por Raios X , Ciclobutanos/síntese química , Ciclobutanos/química , Ciclobutanos/metabolismo , DNA/metabolismo , Depuradores de Radicais Livres/síntese química , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/metabolismo , Humanos , Ligação de Hidrogênio , Substâncias Intercalantes/síntese química , Substâncias Intercalantes/química , Substâncias Intercalantes/metabolismo , Ligantes , Células MCF-7 , Estrutura Molecular , Ligação Proteica , Soroalbumina Bovina/metabolismo , Estrôncio/química , Água/química
5.
Molecules ; 24(5)2019 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-30823489

RESUMO

In this work, several benzothiazole-based aminosquaraine dyes, displaying strong absorption within the so-called phototherapeutic window (650⁻800 nm), were synthesized. The ability, of all the new dyes, to generate singlet oxygen was assessed by determining the correspondent phosphorescence emission and through the comparison with a standard. The quantum yields of singlet oxygen generation were determined and exhibited to be strongly dependent on the nature of the amino substituents introduced in the squaric ring. The photodynamic activity of the synthesized dyes was tested against four human tumor cell lines: breast (MCF-7), lung (NCI-H460), cervical (HeLa) and hepatocellular (HepG2) carcinomas; and a non-tumor porcine liver primary cell culture (PLP2). All the compounds synthesized were found to be able to inhibit tumor cells growth upon irradiation more than in the dark, in most of the cases, very significantly. Considering the photodynamic activity exhibited and the low toxicity displayed for the non-tumor cells, some of the synthetized dyes can be regarded as potential candidates as photosensitizers for PDT.


Assuntos
Ciclobutanos , Citotoxinas , Hidrocarbonetos Iodados , Neoplasias/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes , Animais , Ciclobutanos/síntese química , Ciclobutanos/química , Ciclobutanos/farmacologia , Citotoxinas/síntese química , Citotoxinas/química , Citotoxinas/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Células Hep G2 , Humanos , Hidrocarbonetos Iodados/síntese química , Hidrocarbonetos Iodados/química , Hidrocarbonetos Iodados/farmacologia , Células MCF-7 , Neoplasias/metabolismo , Neoplasias/patologia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Suínos
6.
Methods Mol Biol ; 1954: 77-88, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30864125

RESUMO

Oligosaccharides equipped with amine-containing linkers can be conjugated to carrier proteins using squaric acid chemistry. In a two-step process, a squarate derivative of such oligosaccharide is formed first, which is followed by its reaction with a protein carrier. Monitoring of the conjugation reaction is achieved by SELDI-TOF-MS or MALDI-TOF-MS. This experimentally simple procedure yields desired glycoconjugates in high yields and with reproducible hapten-protein ratios.


Assuntos
Ciclobutanos/química , Glicoconjugados/química , Haptenos/química , Oligossacarídeos/química , Proteínas/química , Soroalbumina Bovina/química , Animais , Bovinos , Cromatografia em Camada Delgada/métodos , Ciclobutanos/síntese química , Glicoconjugados/síntese química , Oligossacarídeos/síntese química , Proteínas/síntese química , Soroalbumina Bovina/síntese química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Ultrafiltração/métodos
7.
Bioorg Med Chem ; 27(5): 865-879, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30728107

RESUMO

Chagas Disease is caused by infection with the insect-transmitted protozoan Trypanosoma cruzi and affects more than 10 million people. It is a paradigmatic example of a chronic disease without an effective treatment in Latin America where the current therapies, based on Benznidazole and Nifurtimox, are characterised by limited efficacy, toxic side-effects and frequent failures in the treatment. We present a series of new long-chain squaramides, identified based on their 1H and 13C NMR spectra, and their trypanocidal activity and cytotoxicity were tested in vitro through the determination of IC50 values. Compounds 4 and 7 were more active and less toxic than the reference drug Benznidazole, and these results were the basis of promoting in vivo assays, where parasitaemia levels, assignment of cure, reactivation of parasitaemia and others parameters were determined in mice treated in both the acute and chronic phases. Finally, the mechanisms of action were elucidated at metabolic and mitochondrial levels and superoxide dismutase inhibition. The experiments allowed us to select compound 7 as a promising candidate for treating Chagas Disease, where the activity, stability and low cost make long-chain squaramides appropriate molecules for the development of an affordable anti-chagasic agent versus current treatments.


Assuntos
Doença de Chagas/tratamento farmacológico , Ciclobutanos/uso terapêutico , Tripanossomicidas/uso terapêutico , Animais , Chlorocebus aethiops , Ciclobutanos/síntese química , Ciclobutanos/toxicidade , DNA/metabolismo , Feminino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos Endogâmicos BALB C , RNA/metabolismo , Esplenomegalia/tratamento farmacológico , Superóxido Dismutase/metabolismo , Tripanossomicidas/síntese química , Tripanossomicidas/toxicidade , Trypanosoma cruzi/efeitos dos fármacos , Células Vero
8.
Bioorg Med Chem ; 27(4): 579-588, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30626555

RESUMO

The antioxidant natural product sulforaphane (SFN) is an oil with poor aqueous and thermal stability. Recent work with SFN has sought to optimize methods of formulation for oral and topical administration. Herein we report the design of new analogs of SFN with the goal of improving stability and drug-like properties. Lead compounds were selected based on potency in a cellular screen and physicochemical properties. Among these, 12 had good aqueous solubility, permeability and long-term solid-state stability at 23 °C. Compound 12 also displayed comparable or better efficacy in cellular assays relative to SFN and had in vivo activity in a mouse cigarette smoke challenge model of acute oxidative stress.


Assuntos
Antioxidantes/farmacologia , Ciclobutanos/farmacologia , Descoberta de Drogas , Isotiocianatos/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Antioxidantes/síntese química , Antioxidantes/farmacocinética , Linhagem Celular , Ciclobutanos/síntese química , Ciclobutanos/farmacocinética , Expressão Gênica , Heme Oxigenase-1/genética , Humanos , Isotiocianatos/síntese química , Isotiocianatos/farmacocinética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Camundongos Endogâmicos C57BL , Estrutura Molecular , Estresse Oxidativo/efeitos dos fármacos , Ratos , Solubilidade , Relação Estrutura-Atividade , Tiocarbamatos/síntese química , Tiocarbamatos/farmacocinética , Tiocarbamatos/farmacologia
9.
Photochem Photobiol Sci ; 18(2): 336-342, 2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30310913

RESUMO

Squaraine dyes have recently attracted interest as potential second generation photosensitizers for photodynamic therapy. Several cationic aminosquaraine dyes bearing benzoselenazole terminal nuclei were synthezised and their cytotoxic activity was tested against four different human tumor cell lines - breast (MCF-7), non-small cell lung (NCI-H460), cervical (HeLa) and hepatocellular (HepG2) carcinomas - and against a non-tumor porcine liver primary cell line (PLP2), both in the absence of light and under irradiation. All dyes, which displayed strong absorption within the phototherapeutic window, were found to exhibit photodynamic activity and were shown to be, in most cases, more cytotoxic, both in the dark and upon irradiation, than their benzothiazole analogues.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Ciclobutanos/síntese química , Ciclobutanos/farmacologia , Fenóis/síntese química , Fenóis/farmacologia , Processos Fotoquímicos , Selênio/química , Antineoplásicos/química , Linhagem Celular Tumoral , Técnicas de Química Sintética , Ciclobutanos/química , Humanos , Fenóis/química
10.
J Am Chem Soc ; 140(50): 17349-17355, 2018 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-30517785

RESUMO

The nickel-catalyzed synthesis of tetrasubstituted cyclobutenes from alkynes is reported. This transformation is uniquely promoted by the use of a primary aminophosphine, an unusual ligand in nickel catalysis. Mechanistic insights for this new transformation are provided, and postreaction modifications of the cyclobutene products to stereodefined cyclic and acyclic compounds are reported, including the synthesis of epi-truxillic acid.


Assuntos
Alquinos/química , Níquel/química , Catálise , Reação de Cicloadição , Ciclobutanos/síntese química , Ligantes , Modelos Químicos , Oxirredução , Fosfinas/química
11.
Chem Commun (Camb) ; 54(95): 13395-13398, 2018 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-30426114

RESUMO

We introduce a novel strategy to enhance the fluorescence brightness of organic-molecule-based nanoparticles in the second near-infrared window (NIR-II, 1000-1700 nm) by fabricating J-aggregate nanoparticles SQP-NPs(J). Our prepared J-aggregate nanoparticles SQP-NPs(J) show an emission maximum near 1100 nm, and the emission intensity is 4.8-fold higher than that of H-aggregate SQP-NPs(H). In addition, SQP-NPs(J) can be used for NIR-II imaging guided photothermal therapy on MCF-7 tumor-bearing mice due to the fact that SQP-NPs(J) have highly effective photothermal properties, which are significant for precise tumor diagnostics and treatments.


Assuntos
Ciclobutanos/uso terapêutico , Corantes Fluorescentes/uso terapêutico , Neoplasias Mamárias Experimentais/diagnóstico por imagem , Neoplasias Mamárias Experimentais/tratamento farmacológico , Nanopartículas/química , Fenóis/uso terapêutico , Fototerapia , Animais , Ciclobutanos/síntese química , Ciclobutanos/química , Feminino , Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Humanos , Raios Infravermelhos , Injeções Intravenosas , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Fenóis/síntese química , Fenóis/química
12.
J Am Chem Soc ; 140(42): 13634-13639, 2018 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-30289691

RESUMO

Substituted 1,3-dienes are valuable synthetic intermediates used in myriad catalytic transformations, yet modern catalytic methods for their preparation in a highly modular fashion using simple precursors are relatively few. We report here an aerobic boron Heck reaction with cyclobutene that forms exclusively linear 1-aryl-1,3-dienes using (hetero)arylboronic acids, or 1,3,5-trienes using alkenylboronic acids, rather than typical Heck products (i.e., substituted cyclobutenes). Experimental and computational mechanistic data support a pericyclic mechanism for C-C bond cleavage that enables the cycloalkene to circumvent established limitations associated with diene reagents in Heck-type reactions.


Assuntos
Alcenos/síntese química , Ácidos Borônicos/química , Alcenos/química , Ácidos Borônicos/síntese química , Técnicas de Química Sintética , Ciclobutanos/síntese química , Ciclobutanos/química , Oxigênio/química , Estereoisomerismo
13.
Artigo em Inglês | MEDLINE | ID: mdl-30188772

RESUMO

A synthesis of cyclobutene nucleoside analogs in which the nucleobase is tethered by a methylene group is described. The coupling of 6-chloropurine with 3-hydroxymethyl-cyclobutanone proceeds via its triflate to give both N-7 and N-9 regioisomers with relative yields corresponding to the calculated charge distribution of the 6-chloropurinyl anion. The stereoselective reduction of the N-alkylated ketones yielded quantitatively one stereoisomer in each case. The structural assignments were based on spectroscopic data and single crystal X-ray diffraction. Attempts to photoexcite the N-7 and N-9 ketones in order to promote ring-expansion did not ensue. Preliminary evidence suggests a photodecarbonylation to cyclopropanes took place.


Assuntos
Ciclobutanos/síntese química , Adenina/análogos & derivados , Adenina/síntese química , Adenina/química , Ciclobutanos/química , Nucleosídeos/síntese química , Nucleosídeos/química , Purinas/química , Estereoisomerismo
14.
Angew Chem Int Ed Engl ; 57(31): 9901-9905, 2018 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-29874408

RESUMO

The reaction of an aryne with an alkyne to generate a benzocyclobutadiene (BCB) intermediate is rare. We report here examples of this reaction, revealed by Diels-Alder trapping of the BCB by either pendant or external electron-deficient alkynes. Mechanistic delineation of the reaction course is supported by DFT calculations. A three-component process joining the benzyne first with an electron-rich and then with an electron-poor alkyne was uncovered. Reactions in which the BCB functions in a rarely observed role as a 4π diene component in Diels-Alder reactions are reported. The results also shed new light on aspects of the hexadehydro-Diels-Alder reaction used to generate the benzynes.


Assuntos
Alquinos/química , Ciclobutanos/síntese química , Reação de Cicloadição , Ciclobutanos/química , Teoria da Densidade Funcional , Estrutura Molecular
15.
Eur J Med Chem ; 154: 233-252, 2018 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-29803996

RESUMO

Fatty acid binding proteins (FABPs) serve as critical modulators of endocannabinoid signaling by facilitating the intracellular transport of anandamide and whose inhibition potentiates anandamide signaling. Our previous work has identified a novel small-molecule FABP inhibitor, α-truxillic acid 1-naphthyl monoester (SB-FI-26, 3) that has shown efficacy as an antinociceptive and anti-inflammatory agent in rodent models. In the present work, we have performed an extensive SAR study on a series of 3-analogs as novel FABP inhibitors based on computer-aided inhibitor drug design and docking analysis, chemical synthesis and biological evaluations. The prediction of binding affinity of these analogs to target FABP3, 5 and 7 isoforms was performed using the AutoDock 4.2 program, using the recently determined co-crystal structures of 3 with FABP5 and FABP7. The compounds with high docking scores were synthesized and evaluated for their activities using a fluorescence displacement assay against FABP3, 5 and 7. During lead optimization, compound 3l emerged as a promising compound with the Ki value of 0.21 µM for FABP 5, 4-fold more potent than 3 (Ki, 0.81 µM). Nine compounds exhibit similar or better binding affinity than 3, including compounds 4b (Ki, 0.55 µM) and 4e (Ki, 0.68 µM). Twelve compounds are selective for FABP5 and 7 with >10 µM Ki values for FABP3, indicating a safe profile to avoid potential cardiotoxicity concerns. Compounds 4f, 4j and 4k showed excellent selectivity for FABP5 and would serve as other new lead compounds. Compound 3a possessed high affinity and high selectivity for FABP7. Compounds with moderate to high affinity for FABP5 displayed antinociceptive effects in mice while compounds with low FABP5 affinity lacked in vivo efficacy. In vivo pain model studies in mice revealed that exceeding hydrophobicity significantly affects the efficacy. Thus, among the compounds with high affinity to FABP5 in vitro, the compounds with moderate hydrophobicity were identified as promising new lead compounds for the next round of optimization, including compounds 4b and 4j. For select cases, computational analysis of the observed SAR, especially the selectivity of new inhibitors to particular FABP isoforms, by comparing docking poses, interaction map, and docking energy scores has provided useful insights.


Assuntos
Analgésicos/farmacologia , Ciclobutanos/farmacologia , Ésteres/farmacologia , Proteínas de Ligação a Ácido Graxo/antagonistas & inibidores , Analgésicos/síntese química , Analgésicos/química , Animais , Desenho Assistido por Computador , Ciclobutanos/síntese química , Ciclobutanos/química , Relação Dose-Resposta a Droga , Desenho de Fármacos , Ésteres/síntese química , Ésteres/química , Proteínas de Ligação a Ácido Graxo/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade
16.
Org Biomol Chem ; 16(4): 521-525, 2018 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-29210413

RESUMO

A collection of systematically substituted 3-cyclo-butylcarbamoyl hydantoins was synthesized by a regioselective multicomponent domino process followed by easy coupling reactions. Calculations, NMR studies and X-ray analysis show that these scaffolds are able to project their side chains similar to common secondary structures, such as the α-helix and ß-turn, with favourable enthalpic and entropic profiles.


Assuntos
Ciclobutanos/química , Hidantoínas/química , Peptidomiméticos/química , Ciclobutanos/síntese química , Hidantoínas/síntese química , Ligação de Hidrogênio , Modelos Químicos , Modelos Moleculares , Conformação Molecular , Peptidomiméticos/síntese química
17.
J Am Chem Soc ; 139(39): 13628-13631, 2017 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-28922911

RESUMO

The enantioselective intermolecular gold(I)-catalyzed [2+2] cycloaddition of terminal alkynes and alkenes has been achieved using non-C2-chiral Josiphos digold(I) complexes as catalysts, by the formation of the monocationic complex. This new approach has been applied to the enantioselective total synthesis of rumphellaone A.


Assuntos
Ciclobutanos/síntese química , Ouro/química , Sesterterpenos/síntese química , Catálise , Reação de Cicloadição , Ciclobutanos/química , Estrutura Molecular , Sesterterpenos/química , Estereoisomerismo
18.
Chemistry ; 23(71): 17973-17980, 2017 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-28940842

RESUMO

The design of fluorescent molecular platforms capable of responding to multiple analytes is a topic of great interest. Herein, the use of a Zn2+ -complexed unsymmetrical squaraine dye, Sq-Zn2+ , as a chemical platform for recognizing structurally distinct analytes is reported. The squaraine ring is substituted on one side with a dipicolylamine unit, which acts as the metal ion receptor, whereas the other part of the molecule carries a dibutylaniline moiety, which is an electron donor. The molecular system is unique because it can respond specifically to different types of analytes, namely, atmospheric carbon dioxide, cyclic phosphates, and picric acid. Moreover, the interaction of these analytes can be monitored colorimetrically and fluorimetrically, which favors both qualitative and quantitative analyses. The distinct response towards cyclic and linear phosphates, as well as the selective response towards picric acid, among the various nitroaromatic compounds was achieved with sensitivity at the ppm level. The flexible coordination offered by Zn2+ plays a significant role in the discrimination of these analytes with high specificity. Dye Sq-Zn2+ introduced herein is a single-molecule construct that can be used for the selective and sensitive response towards analytes of environmental and biological relevance.


Assuntos
Ciclobutanos/química , Corantes Fluorescentes/química , Fenóis/química , Dióxido de Carbono/análise , Colorimetria , Ciclobutanos/síntese química , Corantes Fluorescentes/síntese química , Espectroscopia de Ressonância Magnética , Fenóis/síntese química , Fosfatos/análise , Picratos/análise , Termodinâmica , Água/química , Zinco/química
19.
Chem Commun (Camb) ; 53(76): 10604-10607, 2017 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-28902227

RESUMO

We have identified an aminoacyl-tRNA synthetase/tRNA pair for the efficient and site-specific incorporation of a cyclobutene-containing amino acid into proteins in response to an amber nonsense codon. Fast and fluorescent labeling of purified proteins and intact proteins in live cells was demonstrated using the inverse electron demand Diels-Alder reaction with a tetrazine.


Assuntos
Aminoacil-tRNA Sintetases/genética , Códon sem Sentido/genética , Ciclobutanos/química , Escherichia coli/citologia , Corantes Fluorescentes/química , RNA de Transferência/genética , Aminoácidos/química , Aminoacil-tRNA Sintetases/química , Aminoacil-tRNA Sintetases/metabolismo , Sobrevivência Celular , Reação de Cicloadição , Ciclobutanos/síntese química , Elétrons , Corantes Fluorescentes/síntese química , Proteínas de Fluorescência Verde/química , Modelos Moleculares , Estrutura Molecular , RNA de Transferência/química , RNA de Transferência/metabolismo , Coloração e Rotulagem
20.
Bioorg Med Chem Lett ; 27(18): 4467-4470, 2017 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-28807437

RESUMO

The synthesis of several aminosquaraine cationic dyes displaying strong absorption within the so-called phototherapeutic window (650-850nm) is described. Their cytotoxicity, under dark and illuminated conditions, was tested against several human tumor cell lines (breast, lung, cervical and hepatocellular carcinomas) and non-tumor porcine liver primary cells. All compounds showed to inhibit the growth of the tumor cells upon irradiation more than in the absence of light, in more or less extension, clearly exhibiting photodynamic activity. The photosensitizing ability against some cell lines, together with the low toxicity for the non-tumor primary PLP2 cells displayed by some of the compounds synthetized, turns them into potential candidates as photosensitizers for PDT.


Assuntos
Antineoplásicos/farmacologia , Ciclobutanos/farmacologia , Fenóis/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Ciclobutanos/síntese química , Ciclobutanos/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Fenóis/síntese química , Fenóis/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Relação Estrutura-Atividade , Suínos
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