Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 351
Filtrar
Filtros adicionais











Intervalo de ano
1.
Chem Commun (Camb) ; 55(58): 8434-8437, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31259350

RESUMO

Phosphatidylcholine is the main component of liposomes and other phospholipid-based nanocarriers in drug delivery. However, the functions and applications of these nanocarriers are extremely limited by conventional phospholipids. Here we report novel disulfide phosphatidylcholines (SS-PCs) and SS-PC based liposomes (SS-LPs) used as alternatives to traditional phospholipids and liposomes.


Assuntos
Dissulfetos/química , Portadores de Fármacos/química , Lipossomos/química , Fosfatidilcolinas/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Dissulfetos/síntese química , Dissulfetos/metabolismo , Doxorrubicina/química , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Portadores de Fármacos/síntese química , Portadores de Fármacos/metabolismo , Humanos , Lipossomos/síntese química , Lipossomos/metabolismo , Camundongos , Oxirredução , Fosfatidilcolinas/síntese química , Fosfatidilcolinas/metabolismo
2.
Chem Commun (Camb) ; 55(65): 9653-9656, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31342021

RESUMO

The fast and accurate real-time monitoring of hydrogen peroxide (H2O2) secreted from living cells plays a critical role in clinical diagnosis and management. Herein, we report low-cost and self-supported MoS2 nanosheet arrays for non-enzymatic eletrochemical H2O2 detection. Under the optimal test conditions, such MoS2 electrodes exhibit extremely promising electrocatalytic performance with a low detection limit of 1.0 µM (S/N = 3) and an excellent sensitivity of 5.3 mA mM-1 cm-2. Furthermore, the detection of the trace amount of H2O2 secreted from live A549 cancer cells was successfully performed with this biosensor.


Assuntos
Dissulfetos/química , Peróxido de Hidrogênio/análise , Molibdênio/química , Nanoestruturas/química , Células A549 , Técnicas Biossensoriais/métodos , Carbono/química , Dissulfetos/síntese química , Técnicas Eletroquímicas/métodos , Humanos , Limite de Detecção
3.
Biosens Bioelectron ; 132: 248-264, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30878725

RESUMO

Two-dimensional (2D) layered nanomaterials have triggered an intensive interest due to the fascinating physiochemical properties with the exceptional physical, optical and electrical characteristics that transpired from the quantum size effect of their ultra-thin structure. Among the family of 2D nanomaterials, molybdenum disulfide (MoS2) features distinct characteristics related to the existence of direct energy bandgap, which significantly lowers the leakage current and surpasses other 2D materials. In this overview, we expatiate the novel strategies to synthesize MoS2 that cover techniques such as liquid exfoliation, chemical vapour deposition, mechanical exfoliation, hydrothermal reaction, and Van Der Waal epitaxial growth on the substrate. We extend the discussion on the recent progress in biosensing applications of the produced MoS2, highlighting the important surface-to-volume of ultrathin MoS2 structure, which enhances the overall performance of the devices. Further, envisioned the missing piece with the current MoS2-based biosensors towards developing the future strategies.


Assuntos
Técnicas Biossensoriais/métodos , Dissulfetos/química , Molibdênio/química , Nanoestruturas/química , Nanotecnologia/métodos , Animais , Técnicas Biossensoriais/instrumentação , Dissulfetos/síntese química , Desenho de Equipamento , Humanos , Nanoestruturas/ultraestrutura , Nanotecnologia/instrumentação
4.
Colloids Surf B Biointerfaces ; 176: 80-86, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30594706

RESUMO

A metal-inorganic composite, comprises of silver-molybdenum disulfide nanosheets (Ag@MoS2) was synthesized at low temperature. The Ag@MoS2 composite was drop-casted onto a glassy carbon electrode (GCE) for a highly selective dopamine (DA) detection in the presence of interfering compounds such as uric acid (UA) and ascorbic acid (AA). The physicochemical analysis of the nanosheets was carried out with X-ray diffraction, transmission electron microscopy and X-ray photoelectron spectroscopy. The as-prepared Ag@MoS2-modified GCE displayed excellent electrocatalytic activity toward DA oxidation, with a 0.2 µM detection limit at a signal-to-noise ratio of 3 and an extensive linear detection range from 1 µM to 500 µM (R2 = 0.9983). The fabricated non-enzymatic electrochemical sensor demonstrated superior selectivity and stability for the detection of DA with the removal of AA and UA interfering compounds.


Assuntos
Dissulfetos/química , Dopamina/análise , Nanopartículas Metálicas/química , Molibdênio/química , Nanopartículas/química , Prata/química , Dissulfetos/síntese química , Eletrodos , Tamanho da Partícula , Propriedades de Superfície
5.
Drug Dev Res ; 80(1): 171-178, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30565263

RESUMO

Staphylococcus aureus is a WHO Priority II pathogen for its capability to cause acute to chronic infections and to resist antibiotics, thus severely impacting healthcare systems worldwide. In this context, it is urgently desired to discover novel molecules to thwart the continuing emergence of antimicrobial resistance. Disulphide containing small molecules has gained prominence as antibacterials. As their conventional synthesis requires tedious synthetic procedure and sometimes toxic reagents, a green and environmentally benign protocol for their synthesis has been developed through which a series of molecules were obtained and evaluated for antibacterial activity against ESKAPE pathogen panel. The hit compound was tested for cytotoxicity against Vero cells to determine its selectivity index and time-kill kinetics was determined. The activity of hit was determined against a panel of S. aureus multi-drug resistant clinical isolates. Also, its ability to synergize with FDA approved drugs was tested as was its ability to reduce biofilm. We identified bis(2-bromophenyl) disulphide (2t) as possessing equipotent antimicrobial activity against S. aureus including MRSA and VRSA strains. Further, 2t exhibited a selectivity index of 25 with concentration-dependent bactericidal activity, synergized with all drugs tested and significantly reduced preformed biofilm. Taken together, 2t exhibits all properties to be positioned as novel scaffold for anti-staphylococcal therapy.


Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Biocatálise , Dissulfetos/síntese química , Dissulfetos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Staphylococcus aureus Resistente à Meticilina/fisiologia , Testes de Sensibilidade Microbiana/métodos
6.
Chem Commun (Camb) ; 54(93): 13072-13075, 2018 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-30280156

RESUMO

A new DNA binding small molecule, NCD-CC is reported. NCD-CC has a NCD domain, which recognizes the G-G mismatch in a CGG/CGG triad, and a cysteinylcystein (CC) moiety. Dimerization of NCD-CC through intermolecular disulfide bond formation was accelerated in the presence of CGG repeat DNA.


Assuntos
DNA/química , Dipeptídeos/química , Dissulfetos/síntese química , Naftiridinas/química , Sítios de Ligação , Dimerização , Dissulfetos/química , Humanos , Estrutura Molecular , Repetições de Trinucleotídeos
7.
Chemistry ; 24(59): 15868-15878, 2018 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-30091228

RESUMO

Abnormal H2 O2 and cholesterol levels are closely related to many diseases. This work reports a facile process for the synthesis of oxidized glutathione (GSSG)-modified MoS2 nanosheets (MoS2 -GSSG NSs). The biocompatible MoS2 -GSSG NSs have good dispersibility and high affinity to the substrate 3,3',5,5'-tetramethylbenzidine (TMB), which is beneficial for improving peroxidase-like catalytic activity of MoS2 . The high peroxidase-like activity of MoS2 -GSSG NSs was applied as a robust nanoplatform for low-cost, rapid, and highly effective colorimetric detection of H2 O2 and total/free cholesterol. Moreover, the peroxidase-like catalytic mechanism was studied by the steady-state kinetics method. The catalytic activity was remarkably high at a wide range of pH (2.4-7.0) and temperature values (25-70 °C). The cholesterol was catalyzed by cholesterol oxidase (ChOx) in the presence of O2 to generate H2 O2 , which oxidized TMB to generate a blue-colored product (oxTMB) under the catalysis of MoS2 -GSSG NSs. The detection limit (DL) of total cholesterol and H2 O2 was as low as 5.36 and 0.51 µm, respectively. The linear ranges for detecting cholesterol and H2 O2 were from 5.36 to 800 µm and from 0.51 to 50 µm, respectively. This method was also successfully applied to the detection of cholesterol in serum. The detection concentration of total cholesterol was consistent with that of the value detected by the blood biochemical method used in the clinic.


Assuntos
Técnicas Biossensoriais/métodos , Colesterol/sangue , Dissulfetos/síntese química , Peróxido de Hidrogênio/análise , Nanoestruturas/química , Animais , Catálise , Sobrevivência Celular , Colorimetria , Glutationa/química , Células Endoteliais da Veia Umbilical Humana , Humanos , Cinética , Limite de Detecção , Camundongos Obesos , Molibdênio , Oxirredução , Tamanho da Partícula , Peroxidases/metabolismo , Propriedades de Superfície , Temperatura Ambiente
8.
Chem Commun (Camb) ; 54(68): 9462-9465, 2018 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-30083687

RESUMO

The synergistic effect of two anticancer drugs can significantly overcome the multidrug resistance of tumor cells and improve the drug bioavailability. Herein, two different anticancer drugs, camptothecin and chlorambucil, are successfully connected together by a disulfide linkage to get a novel drug-drug conjugated prodrug (G). Using water-soluble pillar[6]arene (WP6) as a host molecule, a supramolecular host-guest complex WP6⊃G is formed, which can further self-assemble into supramolecular vesicles in aqueous solution. In the specific microenvironment of cancer cells, the disulfide linkage is destroyed and the two anticancer drugs can be released efficiently to achieve a better synergistic effect than a single anticancer drug. Notably, these prodrug nanocarriers can not only effectively kill the cancer cells but also obviously reduce the undesirable side effects on normal cells.


Assuntos
Antineoplásicos/farmacologia , Camptotecina/farmacologia , Clorambucila/farmacologia , Portadores de Fármacos/química , Compostos de Amônio Quaternário/química , Antineoplásicos/síntese química , Antineoplásicos/metabolismo , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Camptotecina/síntese química , Camptotecina/metabolismo , Camptotecina/toxicidade , Clorambucila/síntese química , Clorambucila/metabolismo , Clorambucila/toxicidade , Dissulfetos/síntese química , Dissulfetos/metabolismo , Dissulfetos/farmacologia , Dissulfetos/toxicidade , Portadores de Fármacos/síntese química , Portadores de Fármacos/toxicidade , Glutationa/metabolismo , Humanos , Células MCF-7 , Tamanho da Partícula , Pró-Fármacos/síntese química , Pró-Fármacos/metabolismo , Pró-Fármacos/farmacologia , Pró-Fármacos/toxicidade , Compostos de Amônio Quaternário/síntese química , Compostos de Amônio Quaternário/toxicidade , Solubilidade , Água/química
9.
Biomater Sci ; 6(8): 2122-2129, 2018 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-29901676

RESUMO

The development of delivery systems for small interfering RNA (siRNA) plays a key role in its clinical application. As the major delivery systems for siRNA, cationic polymer- or lipid-based vehicles are plagued by inherent issues. As proof of concept, a disulfide bond-containing amphiphilic Janus dendrimer (ssJD), which could be conveniently synthesized and readily scaled up with high reproducibility, was explored as a siRNA delivery system to circumvent these issues. The cationic hydrophilic head of this Janus dendrimer ensured strong and stable binding with negatively charged siRNA via electrostatic interactions, and the loaded siRNA was rapidly released from the obtained complexes under a redox environment. Therefore, after efficient internalization into tumor cells, redox-sensitive dendrimersome (RSDs)/siRNA exhibited significantly improved gene silencing efficacy.


Assuntos
Dendrímeros/química , Dissulfetos/química , Técnicas de Transferência de Genes , RNA Interferente Pequeno/genética , Tensoativos/química , Sobrevivência Celular/efeitos dos fármacos , Dendrímeros/síntese química , Dendrímeros/farmacocinética , Dissulfetos/síntese química , Dissulfetos/farmacocinética , Inativação Gênica , Humanos , Interações Hidrofóbicas e Hidrofílicas , Oxirredução , RNA Interferente Pequeno/química , RNA Interferente Pequeno/farmacocinética , Eletricidade Estática , Tensoativos/síntese química , Tensoativos/farmacocinética , Células Tumorais Cultivadas
10.
Chem Commun (Camb) ; 54(49): 6368-6371, 2018 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-29869650

RESUMO

Gene silencing using small interfering RNA (siRNA) is a promising strategy for the treatment of multiple diseases. However, the low in vivo stability of siRNA, its poor pharmacokinetics and inability to penetrate inside cells limit its employment in the clinic. Here, we present a novel redox-sensitive micellar nanopreparation based on a triple conjugate of polyethylene glycol, polyethyleneimine and phosphatidylethanolamine, PEG-SS-PEI-PE (PSSPD). This non-toxic system efficiently condenses siRNA and specifically downregulates target green fluorescent protein (GFP) only under reducing conditions via intracellular siRNA release after de-shielding of PEG due to increased glutathione (GSH) levels characteristic of cancer cells.


Assuntos
Portadores de Fármacos/química , Nanopartículas/química , RNA Interferente Pequeno/química , Animais , Linhagem Celular , Dissulfetos/síntese química , Dissulfetos/química , Dissulfetos/toxicidade , Portadores de Fármacos/síntese química , Portadores de Fármacos/toxicidade , Glutationa/química , Camundongos , Micelas , Nanopartículas/toxicidade , Oxirredução , Tamanho da Partícula , Fosfatidiletanolaminas/síntese química , Fosfatidiletanolaminas/química , Fosfatidiletanolaminas/toxicidade , Polietilenoglicóis/síntese química , Polietilenoglicóis/química , Polietilenoglicóis/toxicidade , Polietilenoimina/síntese química , Polietilenoimina/química , Polietilenoimina/toxicidade
11.
Chem Commun (Camb) ; 54(32): 4029-4032, 2018 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-29619474

RESUMO

Bicyclic peptides have been attractive scaffolds for developing high affinity reagents for biomacromolecules. Here we report a general phage-screening strategy for the development of bicyclic peptide ligands constrained with isomerically-forbidden disulfide bridges without elaborate chemical modifications and recourses to genetic code reprogramming.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/síntese química , Técnicas de Visualização da Superfície Celular/métodos , Dissulfetos/síntese química , Peptídeos Cíclicos/síntese química , Sequência de Aminoácidos , Compostos Bicíclicos Heterocíclicos com Pontes/química , Sequência Consenso , Cisteína/química , Dissulfetos/química , Isomerismo , Proteína 1 Associada a ECH Semelhante a Kelch/química , Ligantes , Oxirredução , Penicilamina/química , Peptídeos Cíclicos/química
12.
Eur J Med Chem ; 137: 450-461, 2017 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-28624700

RESUMO

The worldwide outbreak of severe acute respiratory syndrome (SARS) in 2003 had caused a high rate of mortality. Main protease (Mpro) of SARS-associated coronavirus (SARS-CoV) is an important target to discover pharmaceutical compounds for the therapy of this life-threatening disease. During the course of screening new anti-SARS agents, we have identified that a series of unsymmetrical aromatic disulfides inhibited SARS-CoV Mpro significantly for the first time. Herein, 40 novel unsymmetrical aromatic disulfides were synthesized chemically and their biological activities were evaluated in vitro against SARS-CoV Mpro. These novel compounds displayed excellent IC50 data in the range of 0.516-5.954 µM. Preliminary studies indicated that these disulfides are reversible and mpetitive inhibitors. A possible binding mode was generated via molecular docking simulation and a comparative field analysis (CoMFA) model was constructed to understand the structure-activity relationships. The present research therefore has provided some meaningful guidance to design and identify anti-SARS drugs with totally new chemical structures.


Assuntos
Antivirais/farmacologia , Dissulfetos/farmacologia , Descoberta de Drogas , Hidrocarbonetos Aromáticos/farmacologia , Simulação de Acoplamento Molecular , Inibidores de Proteases/farmacologia , Relação Quantitativa Estrutura-Atividade , Vírus da SARS/efeitos dos fármacos , Proteínas Virais/antagonistas & inibidores , Antivirais/síntese química , Antivirais/química , Cisteína Endopeptidases/metabolismo , Dissulfetos/síntese química , Dissulfetos/química , Relação Dose-Resposta a Droga , Hidrocarbonetos Aromáticos/síntese química , Hidrocarbonetos Aromáticos/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Inibidores de Proteases/síntese química , Inibidores de Proteases/química , Vírus da SARS/enzimologia , Proteínas Virais/metabolismo
13.
J Org Chem ; 82(7): 3506-3512, 2017 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-28319665

RESUMO

Naturally occurring, multiple cysteine-containing peptides are a structurally unique class of compounds with a wide range of therapeutic and diagnostic applications. The development of reliable, precise chemical methods for their preparation is of paramount importance to facilitate exploration of their utility. We report here a straightforward and effective approach based on stepwise, sequentially directed disulfide bond formation, exemplified by the synthesis of four-disulfide bond-containing insulin analogs. Cysteine protection consisted of tert-butylthiol (StBu), thiol-trimethoxyphenyl (STmp), trityl (Trt), 4-methoxytrityl (Mmt), S-acetamidomethyl (Acm), and tert-butyl (tBu). This report describes chemistry that is broadly applicable to cysteine-rich peptides and the influence of a fourth disulfide bond on insulin bioactivity.


Assuntos
Dissulfetos/química , Insulina/síntese química , Dissulfetos/síntese química , Humanos , Insulina/análogos & derivados , Insulina/química , Estrutura Molecular
14.
Bioorg Med Chem ; 25(1): 261-268, 2017 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-27865644

RESUMO

The d-/l-peptide gramicidin A (gA) is well known as a pivotal ion channel model and shows a broad spectrum of bioactivities such as antibiosis, antimalarial activity, as well as hemolysis. We applied inter-chain disulfide bonds to constrain the conformational freedom of gA into parallel and antiparallel dimeric topologies. Albeit the constructs were not found to be monoconformational, CD- and IR-spectroscopic studies suggested that this strategy indeed restricted the conformational space of the d-/l-peptide construct, and that ß-helical secondary structures prevail. Correlative testing of gA dimers in antimicrobial, antimalarial, and ion conduction assays suggested that the tail-to-tail antiparallel single stranded ß6.3 helix dominantly mediates the bioactivity of gA. Other conformers are unlikely to contribute to these activities. From these investigations, only weakly ion conducting gA dimers were identified that retained nM antimalarial activity.


Assuntos
Antibacterianos/farmacologia , Antimaláricos/farmacologia , Dissulfetos/farmacologia , Gramicidina/análogos & derivados , Gramicidina/farmacologia , Antibacterianos/síntese química , Antimaláricos/síntese química , Dicroísmo Circular , Dimerização , Dissulfetos/síntese química , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Gramicidina/síntese química , Hemólise , Membranas Artificiais , Conformação Molecular , Permeabilidade , Plasmodium falciparum/efeitos dos fármacos
15.
Curr Med Chem ; 24(41): 4627-4637, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27087242

RESUMO

Organic compounds possessing the -S-S- bond, often called disulfide or disulfane, are extremely important and useful in various fields. They often exhibit unique and diverse chemistry in synthetic, biochemical, pharmacological areas as well as are vastly used as vulcanizing agents for rubbers and elastomers. In peptide and protein chemistry, the disulfide bridges impart stability in folding and their synthesis is a pivotal transformation in modern medicinal chemistry research. On the other hand, microwave (MW) provides heat energy source, an alternative to conventional heating, and is used for diverse chemical reactions. This review has presented the progress towards the synthesis of small organic disulfanes and acyclic/cyclic peptides bearing the -S-S- bond specifically under microwave irradiation, which often facilitated the formation of disulfides over conventional heating both in terms of reaction time and efficiency.


Assuntos
Dissulfetos/síntese química , Micro-Ondas , Química Farmacêutica , Dissulfetos/química , Estrutura Molecular
16.
Org Lett ; 18(21): 5516-5519, 2016 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-27754694

RESUMO

A new synthetic route to human relaxin-2 has been established through a sequential disulfide bond formation process in the absence of iodine. It is enabled by a combination of cysteine protection with penicillin G acylase-labile Phacm and a newly identified thiol activator bis(5-(2-methoxyethoxy)-2-pyrimidinyl disulfide. The long-standing challenges in relaxin B-chain assembly and its poor solubility have been solved by the insertion of two isoacyl dipeptide segments. The overall yield was 25% from the B chain and 5.8% from the B-chain starting resin.


Assuntos
Dissulfetos/síntese química , Relaxina/síntese química , Cromatografia Líquida de Alta Pressão , Dissulfetos/química , Humanos , Iodo/química , Estrutura Molecular , Relaxina/química , Solubilidade
17.
Chemistry ; 22(50): 18085-18091, 2016 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-27797427

RESUMO

The ability to reversibly cross-link proteins and peptides grants the amino acid cysteine its unique role in nature as well as in peptide chemistry. We report a novel class of S-alkylsulfonyl-l-cysteines and N-carboxy anhydrides (NCA) thereof for peptide synthesis. The S-alkylsulfonyl group is stable against amines and thus enables its use under Fmoc chemistry conditions and the controlled polymerization of the corresponding NCAs yielding well-defined homo- as well as block co-polymers. Yet, thiols react immediately with the S-alkylsulfonyl group forming asymmetric disulfides. Therefore, we introduce the first reactive cysteine derivative for efficient and chemoselective disulfide formation in synthetic polypeptides, thus bypassing additional protective group cleavage steps.


Assuntos
Anidridos/química , Cisteína/química , Dissulfetos/química , Peptídeos/química , Compostos de Sulfidrila/química , Aminas , Dissulfetos/síntese química , Polimerização
18.
Anal Chim Acta ; 937: 87-95, 2016 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-27590549

RESUMO

This paper reports a facile synthesis of molybdenum disulfide nanosheets/silver nanoparticles (MoS2/Ag) hybrid and its use as an effective matrix in negative ion matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The nanohybrid exerts a strong synergistic effect, leading to high performance detection of small molecule analytes including amino acids, peptides, fatty acids and drugs. The enhancement of laser desorption/ionization (LDI) efficiency is largely attributed to the high surface roughness and large surface area for analyte adsorption, better dispersibility, increased thermal conductivity and enhanced UV energy absorption as compared to pure MoS2. Moreover, both Ag nanoparticles and the edge of the MoS2 layers function as deprotonation sites for proton capture, facilitating the charging process in negative ion mode and promoting formation of negative ions. As a result, the MoS2/Ag nanohybrid proves to be a highly attractive matrix in MALDI-TOF MS, with desired features such as high desorption/ionization efficiency, low fragmentation interference, high salt tolerance, and no sweet-spots for mass signal. These characteristic properties allowed for simultaneous analysis of eight different drugs and quantification of acetylsalicylic acid in the spiked human serum. This work demonstrates for the first time the fabrication and application of a novel MoS2/Ag hybrid, and provides a new platform for use in the rapid and high throughput analysis of small molecules by mass spectrometry.


Assuntos
Amoxicilina/análise , Ampicilina/análise , Nanopartículas/química , Bibliotecas de Moléculas Pequenas/análise , Sulfametazina/análise , Sulfametoxazol/análise , Aspirina/sangue , Dissulfetos/síntese química , Dissulfetos/química , Humanos , Molibdênio/química , Tamanho da Partícula , Prata/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
19.
Bioorg Med Chem Lett ; 26(17): 4372-6, 2016 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-27460171

RESUMO

In this study, a concise synthetic method of psammaplin A was achieved from 3-bromo-4-hydroxybenzaldahyde and hydantoin through a four-step synthesis via Knoevenagel condensation, hydrolysis, oximation and amidation in 37% overall yield. A collection of novel psammaplin A analogs focused on the variations of substituents at the benzene ring and modifications at the oxime moiety were synthesized. Among all the synthesized compounds, 5d and 5e showed better HDAC inhibition than psammaplin A and comparable cytotoxicity against four cancer cell lines (PC-3, MCF-7, A549 and HL-60). Molecular docking and dynamics simulation revealed that (i) hydrogen atom of the oxime group interacts with Asp99 of HDAC1 through a water bridged hydrogen bond and (ii) a hydroxyl group is optimal attached on the para-position of benzene, interacting with Glu203 at the entrance to the active site tunnel.


Assuntos
Dissulfetos/síntese química , Dissulfetos/farmacologia , Inibidores de Histona Desacetilases , Simulação de Acoplamento Molecular , Tirosina/análogos & derivados , Citotoxinas/síntese química , Citotoxinas/química , Citotoxinas/farmacologia , Dissulfetos/química , Ativação Enzimática/efeitos dos fármacos , Inibidores de Histona Desacetilases/síntese química , Inibidores de Histona Desacetilases/química , Inibidores de Histona Desacetilases/farmacologia , Humanos , Tirosina/síntese química , Tirosina/química , Tirosina/farmacologia
20.
Bioorg Chem ; 68: 15-22, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27414468

RESUMO

Novel series of disulfide and sulfone hybrid analogs (1-20) were synthesized and characterized through EI-MS and (1)H NMR and evaluated for ß-glucuronidase inhibitory potential. All synthesized analogs except 13 and 15 showed excellent ß-glucuronidase inhibitory potential with IC50 value ranging in between 2.20-88.16µM as compared to standard d-saccharic acid 1,4 lactone (48.4±1.25µM). Analogs 19, 16, 4, 1, 17, 6, 10, 3, 18, 2, 11, 14 and 5 showed many fold potent activity against ß-glucuronidase inhibitor. Structure activity relationship showed that substitution of electron withdrawing groups at ortho as well as para position on phenyl ring increase potency. Electron withdrawing groups at meta position on phenyl ring showed slightly low potency as compared to ortho and para position. The binding interactions were confirmed through molecular docking studies.


Assuntos
Dissulfetos/farmacologia , Glucuronidase/antagonistas & inibidores , Glicoproteínas/farmacologia , Sulfonas/farmacologia , Dissulfetos/síntese química , Dissulfetos/química , Relação Dose-Resposta a Droga , Glucuronidase/metabolismo , Glicoproteínas/síntese química , Glicoproteínas/química , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade , Sulfonas/síntese química , Sulfonas/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA