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1.
Chem Pharm Bull (Tokyo) ; 68(2): 173-178, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32009085

RESUMO

An ion-channel-forming natural peptide, gramicidin A (1), exhibits potent antimicrobial activity against Gram-positive bacteria, although medical applications are limited to topical use due to its mammalian cytotoxicity. We recently reported that the artificial macrocyclic analogue 2 provides a promising starting point for developing new ion-channel-based systemic antibacterial agents because of its low mammalian cytotoxicity compared to that of the parent 1. To dissect the molecular factors involved in the species selectivity of 2, we evaluated the ion transport activities, phospholipid affinities, and conformational properties of 1 and 2 using various compositions of phospholipids. A combination of lipid dot blot assays and circular dichroism (CD) analysis with H+/Na+ exchange assays revealed that the higher H+/Na+ exchange activity of 2 than that of 1 in liposomes containing 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) or 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (POPG) is attributable to its higher affinity towards the phospholipids than that of 1. Notably, we also discovered that 2 showed weaker H+/Na+ exchange activity in liposomes containing 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylethanolamine (POPE). CD analysis of 2 in liposomes indicated that the weak H+/Na+ exchange activity is induced by disturbance of the ion-conducting ß6.3-helical conformation in the POPE-containing lipid bilayer. These results suggest that the POPE-induced attenuation of the ion-conducting activity of 2 contributes to the alleviation of undesirable mammalian cytotoxicity of 2 compared to that of 1.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Gramicidina/análogos & derivados , Gramicidina/farmacologia , Fosfolipídeos/metabolismo , Antibacterianos/toxicidade , Bactérias Gram-Positivas/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Gramicidina/toxicidade , Humanos , Transporte de Íons/efeitos dos fármacos , Bicamadas Lipídicas/metabolismo , Compostos Macrocíclicos/química , Compostos Macrocíclicos/farmacologia
3.
Chem Soc Rev ; 49(4): 1144-1172, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-31971181

RESUMO

The emergence of aggregation-induced emission luminogens (AIEgens) has significantly stimulated the development of luminescent supramolecular materials because their strong emissions in the aggregated state have resolved the notorious obstacle of the aggregation-caused quenching (ACQ) effect, thereby enabling AIEgen-based supramolecular materials to have a promising prospect in the fields of luminescent materials, sensors, bioimaging, drug delivery, and theranostics. Moreover, in contrast to conventional fluorescent molecules, the configuration of AIEgens is highly twisted in space. Investigating AIEgens and the corresponding supramolecular materials provides fundamental insights into the self-assembly of nonplanar molecules, drastically expands the building blocks of supramolecular materials, and pushes forward the frontiers of supramolecular chemistry. In this review, we will summarize the basic concepts, seminal studies, recent trends, and perspectives in the construction and applications of AIEgen-based supramolecular materials with the hope to inspire more interest and additional ideas from researchers and further advance the development of supramolecular chemistry.


Assuntos
Substâncias Luminescentes/química , Imagem Óptica , Nanomedicina Teranóstica , DNA/química , Portadores de Fármacos/química , Humanos , Compostos Macrocíclicos/química , Microscopia Confocal , Neoplasias/diagnóstico por imagem , Peptídeos/química
4.
Chemphyschem ; 21(3): 257-262, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-31793133

RESUMO

The choice between adaptive and preorganized architectures, or of the most effective hydrogen bonding groups to be selected, are dilemmas that supramolecular chemists must address in designing synthetic receptors for such a challenging guest as carbohydrates. In this paper, structurally related architectures featuring two alternative hydrogen bonding motifs were compared to ascertain the structural and functional origin of their binding differences and the advantages that can be expected in monosaccharide recognition. A set of structurally related macrocyclic receptors were prepared, and their binding properties were measured by NMR and ITC techniques in chloroform vs a common saccharidic target, namely, the ß-octyl glycoside of D-glucose. Results showed that the diaminocarbazolic motif, recently reported as the constituting unit of highly effective receptors for saccharides in water, is a superior hydrogen bonding motif compared to the previously described diaminopyrrolic motif, which was successfully employed in molecular recognition of carbohydrates in polar organic solvents, due to intrinsic structural and functional factors, rather than to hydrophobic contributions. In addition, the occurrence of a rare example of a thermodynamic template effect exerted by the beta-glucoside has been ascertained, enhancing the synthesis outcome of the otherwise low yielding preparation of the described macrocyclic receptors.


Assuntos
Carbazóis/química , Glucosídeos/química , Compostos Macrocíclicos/química , Pirróis/química , Receptores Artificiais/química , Ligações de Hidrogênio , Ligantes , Conformação Molecular , Termodinâmica
5.
Chemistry ; 26(1): 49-88, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31483909

RESUMO

Drugs in the chemical space beyond the rule of 5 (bRo5) can modulate targets with difficult binding sites while retaining cell permeability and oral absorption. Reviewing the syntheses of bRo5 drugs approved since 1990 highlights synthetic chemistry's contribution to drug discovery in this space. Initially, bRo5 drugs were mainly natural products and semi-synthetic derivatives. Later, peptidomimetics and de novo designed compounds, that include up to seven chiral centres and macrocyclic rings became dominant. These drugs are prepared by total synthesis, sometimes by routes of more than 25 steps with stereocentres originating from the chiral pool, or being installed by chiral induction or enzymatic resolution. Interestingly, ring-closing metathesis proved to be the method of choice for macrocyclisation in hepatitis C virus protease inhibitors. We conclude that structural simplification, planning of synthetic routes regarding incorporation of stereocentres and macrocyclisation, as well as incorporation of structural knowledge and consideration of chameleonic properties in design, should facilitate drug discovery in bRo5 space.


Assuntos
Descoberta de Drogas , Preparações Farmacêuticas/síntese química , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Sítios de Ligação , Hepacivirus/enzimologia , Compostos Macrocíclicos/síntese química , Compostos Macrocíclicos/química , Compostos Macrocíclicos/metabolismo , Peptidomiméticos , Preparações Farmacêuticas/química , Preparações Farmacêuticas/metabolismo , Inibidores de Proteases/síntese química , Inibidores de Proteases/química , Inibidores de Proteases/metabolismo , Ribossomos/química , Ribossomos/metabolismo , Proteínas Virais/química , Proteínas Virais/metabolismo
6.
J Photochem Photobiol B ; 203: 111739, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31855719

RESUMO

A mono-N-substituted probe L containing a bromosalicylaldehyde pendant arm attached to a tetraazamacrocyclic "tet a" moiety was synthesized via straight forward reaction. The probe L crystallizes in a monoclinic P21/n space group. The probe L displayed quick sensitivity and selectivity towards Hg2+ ions due to its hopeful Chelation Enhancement Quenching (CHEQ) feature. Interestingly, the probe L exhibits turn-off fluorescence response to Hg2+ ion and turn-on fluorescence signals to HSO4- ions. When the probe L was complexed with HSO4- in 1:1 mode (L + HSO4- formation), improved turn-on fluorescence emission was detected due to the chelation enhanced fluorescence effect through sensor complex. The macrocyclic "tet a" probe L exhibited a binding constant value of 3.89 × 106 M-1 and 5.58 × 105 M-1 for Hg2+ and HSO4-, respectively. Probe L exhibited good selectivity to Hg2+ rather than other common metal ions and HSO4- over other common anions. The limit of detection (LOD) of Hg2+ and HSO4- were found to be 1 nM and 7 µM, respectively. The time-resolved fluorescence emission single-photon counting study was used to determine the average lifetime value for the probe L and L + HSO4- ions as 0.47 and 1.02 ns, respectively. The practical application of the probe in visualizing intracellular Hg2+ and HSO4- ions distribution in live Artemia salina was demonstrated. Furthermore, the probe L with Hg2+cations was found to be cytotoxic against breast cancer cells in nature and can be delivered as an anticancer agent. Besides the probe L with HSO4- exhibit strong fluorescence emission with low cytotoxicity, and it can be recommended for live-cell imaging.


Assuntos
Corantes Fluorescentes/química , Compostos Macrocíclicos/química , Mercúrio/análise , Microscopia de Fluorescência/métodos , Sulfitos/análise , Animais , Ânions/química , Artemia/crescimento & desenvolvimento , Cátions/química , Linhagem Celular Tumoral , Humanos , Larva/química , Larva/metabolismo , Limite de Detecção , Conformação Molecular
7.
Talanta ; 207: 120311, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31594615

RESUMO

Detection of glutathione in human serum is of great importance for clinical diagnosis of various diseases, such as AIDS, diabetes mellitus, Alzheimer disease and cancer. In this work, a new water-soluble bismacrocyclic polyamine-derived compound, namely L, which contains two molecules of 4-nitro-1,2,3-benzoxa-diazole as the fluorophores, was designed and prepared. The experiments of selectivity of L toward metal ions showed it could rapidly and sensitively detect Hg2+ with a detection limit of 27 nM. Furthermore, the cell imaging and co-staining experiments in HeLa cells demonstrated that the L-Hg2+ probe had selectivity for the Golgi apparatus to a certain degree. Moreover, it had excellent selectivity for biothiols, especially for glutathione. Finally, the probe was successfully applied to sensitively detect glutathione (GSH) in human serum and fetal bovine serum.


Assuntos
Corantes Fluorescentes/química , Glutationa/sangue , Limite de Detecção , Compostos Macrocíclicos/química , Mercúrio/sangue , Poliaminas/química , Glutationa/química , Humanos , Mercúrio/química , Imagem Óptica
8.
Chem Commun (Camb) ; 55(95): 14335-14338, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31720600

RESUMO

A syn-atropisomer of naphthalene diimide as a highly preorganized precursor was used to construct a type of trapezoid-shape macrocycle, namely 'trapezoid' molecular boxes (TBox). As supramolecular hosts, TBox can bind electron-rich guests and selectively recognize free tryptophan and tryptophanyl residues from 20 standard amino acids.


Assuntos
Imidas/química , Compostos Macrocíclicos/química , Naftalenos/química , Triptofano/análise
9.
Comput Biol Chem ; 83: 107154, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31751885

RESUMO

Hepatitis C virus (HCV) NS3/4A protease is an attractive target for the development of antiviral therapy. However, the evolution of antiviral drug resistance is a major problem for treatment of HCV infected patients. Understanding of drug-resistance mechanisms at molecular level is therefore very important for the guidance of further design of antiviral drugs with high efficiency and specificity. Paritaprevir is a potent inhibitor against HCV NS3/4A protease genotype 1a. Unfortunately, this compound is highly susceptible to the substitution at D168 in the protease. In this work, molecular dynamics simulations of paritaprevir complexed with wild-type (WT) and two mutated strains (D168 N and D168Y) were carried out. Due to such mutations, the inhibitor-protein hydrogen bonding between them was weakened and the salt-bridge network among residues R123, R155 and D168 responsible for inhibitor binding was disrupted. Moreover, the per-residue free energy decomposition suggested that the main contributions from key residues such as Q80, V132, K136, G137 and R155 were lost in the D168 N/Y mutations. These lead to a lower binding affinity of paritaprevir for D168 N/Y variants of the HCV NS3/4A protease, consistent with the experimental data. This detailed information could be useful for further design of high potency anti-HCV NS3/4A inhibitors.


Assuntos
Antivirais/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Compostos Macrocíclicos/farmacologia , Simulação de Dinâmica Molecular , Mutação , Proteínas não Estruturais Virais/antagonistas & inibidores , Antivirais/química , Farmacorresistência Viral/efeitos dos fármacos , Ligações de Hidrogênio , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Compostos Macrocíclicos/química , Termodinâmica , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo
10.
Molecules ; 24(19)2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31581425

RESUMO

The Cu2+, Mn2+, and Fe3+ complexes of a 14 membered macrocycle were synthesized and their antioxidant capacities were evaluated against ABTS and DPPH radicals, with the objective of collecting insights into the biomimetic role of the central metal ions. The macrocycle, abbreviated as H2L14, is a derivative of EDTA cyclized with 1,4-diamine, and the moderately flexible macrocyclic frame permits the formation of [ML14·H2O] chelates with octahedral coordination geometries common among the metal ions. The metal complexes were characterized by electrospray-ionization mass spectrometry, Fourier transform infrared spectroscopy, and Raman and X-ray photoelectron spectroscopic methods, as well as thermogravimetric analysis; the octahedral coordination geometries with water coordination were optimized by DFT calculations. The antioxidant assays showed that [FeL14·H2O]+ was able to scavenge synthetic radicals with moderate capacity, whereas the other metal chelates did not show significant activity. The Raman spectrum of DPPH in solution suggests that interaction was operative between the Fe3+ chelate and the radical so as to cause scavenging capability. The nature of the central metal ions is a controlling factor for antioxidant capacity, as every metal chelate carries the same coordination geometry.


Assuntos
Antioxidantes/síntese química , Complexos de Coordenação/síntese química , Ácido Edético/química , Compostos Macrocíclicos/síntese química , Antioxidantes/química , Complexos de Coordenação/química , Cobre/química , Teoria da Densidade Funcional , Ferro/química , Compostos Macrocíclicos/química , Manganês/química , Estrutura Molecular , Espectrometria de Massas por Ionização por Electrospray , Espectroscopia de Infravermelho com Transformada de Fourier , Termogravimetria
11.
Int J Mol Sci ; 20(20)2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31618886

RESUMO

The role of metalloproteinases (MMPs) on the migration and invasion of cancer cells has been correlated with tumor aggressiveness, namely with the up-regulation of MMP-2 and 9. Herein, two pyridine-containing macrocyclic compounds, [15]pyN5 and [16]pyN5, were synthesized, chemically characterized and evaluated as potential MMP inhibitors for breast cancer therapy using 3D and 2D cellular models. [15]pyN5 and [16]pyN5 (5-20 µM) showed a marked inhibition of MMPs activity (100% at concentrations ≥ 7.5 µM) when compared to ARP-100, a known MMP inhibitor. The inhibitory activity of [15]pyN5 and [16]pyN5 was further supported through in silico docking studies using Goldscore and ChemPLP scoring functions. Moreover, although no significant differences were observed in the invasion studies in the presence of all MMPs inhibitors, cell migration was significantly inhibited by both pyridine-containing macrocycles at concentrations above 5 µM in 2D cells (p < 0.05). In spheroids, the same effect was observed, but only with [16]pyN5 at 20 µM and ARP-100 at 40 µM. Overall, [15]pyN5 and [16]pyN5 led to impaired breast cancer cell migration and revealed to be potential inhibitors of MMPs 2 and 9.


Assuntos
Compostos Macrocíclicos/farmacologia , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz/farmacologia , Piridinas/farmacologia , Sítios de Ligação , Catálise , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Compostos Macrocíclicos/química , Metaloproteinase 2 da Matriz/química , Metaloproteinase 9 da Matriz/química , Inibidores de Metaloproteinases de Matriz/química , Modelos Moleculares , Estrutura Molecular , Ligação Proteica , Piridinas/química , Relação Estrutura-Atividade , Células Tumorais Cultivadas , Zinco/química
12.
Chem Commun (Camb) ; 55(79): 11924-11927, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31528965

RESUMO

We report a novel ditopic Gd(iii)-based probe selective to zwitterionic amino acid neurotransmitters (ZNTs) crafted for ratiometric MRI imaging. The probe displayed increased binding affinity to ZNTs and non-synchronized concentration-dependent changes of the r1- and r2-relaxivity. Through the application of a T2/T1 weighted MRI strategy, we demonstrated signal enhancement for cooperatively bound glutamate and γ-aminobutyric acid ZNTs over competitive hydrogencarbonate, which remained MR silent.


Assuntos
Aminoácidos/química , Meios de Contraste/química , Complexos de Coordenação/química , Gadolínio/química , Imagem por Ressonância Magnética/métodos , Neurotransmissores/análise , Bicarbonatos/análise , Técnicas Biossensoriais/métodos , Ácido Glutâmico/análise , Ligantes , Compostos Macrocíclicos/química , Peso Molecular , Ácido gama-Aminobutírico/análise
13.
Mater Sci Eng C Mater Biol Appl ; 105: 110119, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31546342

RESUMO

A series of CuII, CoII, ZnII and NiII, complexes of 34,74-dimethyl-12,15,52,55-tetrahydro-2,4,6,8-tetraaza-1,5(2,5)-difurana-3,7(1,2)-dibenzenacyclooctaphane based ligand have been synthesized by template methodology. Characterization of the synthesized complexes has been carried out with the help of various physicochemical and spectroscopic techniques like Infra-Red, ESI-MS, ESR, UV-visible, CHN (elemental analyses), molar conductance, magnetic moment and NMR. Antimicrobial efficacy of the newly designed macrocyclic complexes has performed by the assistance of agar well diffusion method. In-vitro hemolytic and DNA binding studies were also performed in order to analyze or interpret the mode and binding efficiencies as well as the % hemolysis exhibited by the complexes. DFT/TD-DFT studies were carried out in order to elucidate the better insight into the structural parameters. Energy minimization and quantum chemical parameters were calculated using Gaussian09W program.


Assuntos
Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Compostos Macrocíclicos/síntese química , Compostos Macrocíclicos/farmacologia , Bases de Schiff/síntese química , Bases de Schiff/farmacologia , Animais , Anti-Infecciosos/química , DNA/metabolismo , Espectroscopia de Ressonância de Spin Eletrônica , Peixes , Hemólise/efeitos dos fármacos , Compostos Macrocíclicos/química , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Conformação Molecular , Bases de Schiff/química , Espectrofotometria Infravermelho
14.
J Chromatogr A ; 1604: 460485, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31477276

RESUMO

Macrocyclic glycopeptides have been used as chromatographic stationary phases for over twenty years, particularly for their ability to separate enantiomers. While they are mostly used with buffered aqueous liquid mobile phases, they can also be used in supercritical fluid chromatography (SFC) with mobile phases comprising pressurized carbon dioxide and a co-solvent (like methanol), possibly comprising acidic or basic additives. In the present study, we compared three macrocyclic glycopeptide stationary phases (Chirobiotic V2, Chirobiotic T and Chirobiotic TAG) in SFC with carbon dioxide - methanol (90:10) containing no additives. First, the interactions contributing to retention are evaluated with a modified version of the solvation parameter model, comprising five Abraham descriptors (E, S, A, B, V) and two additional descriptors to take account of interactions with ionizable species (D- and D+). Linear solvation energy relationships (LSER) are established based on the retention of 145 achiral analytes. Secondly, the contributions of interactions to enantioseparations are discussed, based on the analysis of 67 racemates. The individual success rate on each phase was observed to be moderate, especially as these phases are known to be more efficient when acidic or basic additives are employed. Chirobiotic TAG proved more successful than the other two phases. Discriminant analyses were computed to gain some insight on retention mechanisms, but only Chirobiotic TAG provided interpretable results. Finally, the effects of a small proportion of acidic or basic additive on enantioseparation with Chirobiotic T stationary phase are briefly discussed.


Assuntos
Cromatografia com Fluido Supercrítico/métodos , Glicopeptídeos/química , Compostos Macrocíclicos/química , Análise Discriminante , Concentração de Íons de Hidrogênio , Solventes , Estereoisomerismo
15.
Chem Commun (Camb) ; 55(81): 12235-12238, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31552940

RESUMO

A new calixpyridinium-based light-responsive host-guest recognition motif was found in this work. This host-guest recognition motif was further discovered to be applied as a selective turn-on fluorescent sensor for lysine over other natural amino acids.


Assuntos
Corantes Fluorescentes/química , Lisina/química , Compostos Macrocíclicos/química , Fotólise , Compostos de Piridínio/química , Técnicas Biossensoriais/métodos , Interações Hidrofóbicas e Hidrofílicas , Conformação Molecular , Espectrometria de Fluorescência , Água
16.
Chemistry ; 25(58): 13275-13279, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31398268

RESUMO

Manipulation of the emerging anion-π interactions in a highly cooperative manner through sophisticated host design represents a very challenging task. In this work, unprecedented tetrahedral anion-π receptors have been successfully constructed for complementary accommodation of tetrahedral and relevant anions. The synthesis was achieved by a macrocycle-directed approach by using large macrocycle precursors bearing four reactive sites, which enabled a kinetic-favored pathway and afforded the otherwise inaccessible tetrahedral cages in considerable yields. Crystal structure suggested that the tetrahedral cages have an enclosed three-dimensional cavity surrounded by four electron-deficient triazine faces in a tetrahedral array. The complementary accommodation of a series of tetrahedral and relevant anions including BF4 - , ClO4 - , H2 PO4 - , HSO4 - , SO4 2- and PF6 - was revealed by ESI-MS and DFT calculations. Crystal structures of ClO4 - and PF6 - complexes showed that the anion was nicely encapsulated within the tetrahedral cavity with up to quadruple cooperative anion-π interactions by an excellent shape and size match. The strong anion-π binding was further confirmed by negative ion photoelectron spectroscopy measurements.


Assuntos
Compostos Macrocíclicos/química , Triazinas/química , Ânions/química , Boratos/química , Reagentes para Ligações Cruzadas/química , Cristalização , Teoria da Densidade Funcional , Estrutura Molecular , Percloratos/química , Espectrometria de Massas por Ionização por Electrospray , Sulfatos/química
17.
Chem Commun (Camb) ; 55(73): 10892-10895, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31436766

RESUMO

Bifunctional supramolecular prodrug vesicles have been successfully constructed based on the complexation between a glutathione (GSH)-responsive prodrug guest molecule (DNS-CPT) and a water-soluble pillar[5]arene (WP5) for cancer diagnosis and therapy. Under the microenvironment of cancer cells with high GSH concentration, 7-ethyl-10-hydroxycamptothecin (SN-38) with strong yellow fluorescence can be efficiently released from the prodrug DNS-CPT for drug location and cancer therapy.


Assuntos
Antineoplásicos/uso terapêutico , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Portadores de Fármacos/química , Compostos Macrocíclicos/química , Pró-Fármacos/uso terapêutico , Animais , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Camptotecina/farmacologia , Camptotecina/toxicidade , Linhagem Celular Tumoral , Portadores de Fármacos/síntese química , Liberação Controlada de Fármacos , Feminino , Glutationa/química , Humanos , Compostos Macrocíclicos/síntese química , Camundongos , Camundongos Endogâmicos BALB C , Células NIH 3T3 , Nanopartículas/química , Tamanho da Partícula , Pró-Fármacos/síntese química , Pró-Fármacos/farmacologia , Pró-Fármacos/toxicidade , Solubilidade , Água , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Molecules ; 24(14)2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31331097

RESUMO

Three (R)-BINOL-based macrocyclic receptors obtained via double-amidation reaction were used for chiral recognition of four anions derived from α-hydroxy and α-amino acids. The structural factors of hosts and guests that affect chiral recognition processes were also investigated, indicating that the proper geometry of both receptor and guest molecules plays a crucial role in effective enantio-discrimination.


Assuntos
Ânions/química , Ácidos Carboxílicos/química , Compostos Macrocíclicos/química , Naftalenos/química , Ciclização , Ligações de Hidrogênio , Estrutura Molecular , Análise Espectral
19.
J Chromatogr A ; 1602: 368-377, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31213361

RESUMO

Chromatographic behaviors of dipeptides consisting of leucine and glycine were studied on two antibiotic-based chiral stationary phases (CSPs) with teicoplanin (Chirobiotic T) or ristocetin A (Chirobiotic R) as chiral selectors under reversed-phase conditions. The effect of mobile phase pH on the retention of stereoisomers of dipeptides was investigated and thermodynamic characteristic of adsorption were measured at different pH values. It was shown that the retention of dipeptides depends on the ionization of their molecules in the mobile phase, as different ionic forms have different affinity towards antibiotic selectors. Enantioselectivity of the bound antibiotics with respect to Leu-Leu stereoisomers was achieved via steric modulation of ion-ion interactions between the solute and the selector, while in the case of Gly-Leu enantiomers non-ionic interactions such as hydrogen bonding might play the key role. In both cases, the dipeptides terminating in D-Leu were retained stronger than their optical antipodes, whereas the enantiomers of Leu-Gly were hardly separated. The regression analysis of the retention data applying the Horvath-Melander-Molnar model revealed that different types of enantioselectivity resides in particular ionic forms of the compounds: cations are responsible for the separation of diastereomeric pairs and the anionic and zwitterionic forms have a universal enantioselectivity on the Chirobiotic T CSP, and the anions and zwitterions are the enantioselective forms for the Chirobiotic R CSP.


Assuntos
Antibacterianos/química , Dipeptídeos/química , Adsorção , Cromatografia Líquida de Alta Pressão/métodos , Glicopeptídeos/química , Ligações de Hidrogênio , Concentração de Íons de Hidrogênio , Cinética , Compostos Macrocíclicos/química , Ristocetina/química , Estereoisomerismo , Teicoplanina/química , Termodinâmica
20.
Chem Commun (Camb) ; 55(56): 8098-8101, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31232416

RESUMO

We report the first macrocycle-based ratiometric molecular thermometer exploiting the conformational thermosensitivity of a calixarene functionalized with two different fluorophores. Thanks to the dependence on temperature of the efficiency of excitation energy transfer between the organic fluorophores, the thermometer works over a 60 °C-wide temperature range with a sensitivity of 4% °C-1.


Assuntos
Calixarenos/química , Corantes Fluorescentes/química , Temperatura Alta , Transferência Ressonante de Energia de Fluorescência , Compostos Macrocíclicos/química , Estrutura Molecular , Espectroscopia de Prótons por Ressonância Magnética , Espectrometria de Massas por Ionização por Electrospray
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