Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 662
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Eur J Med Chem ; 185: 111780, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31655429

RESUMO

Two new series of pyrrolizine-5-carboxamides were synthesized and evaluated for their anticancer and anti-inflammatory activities. The new compounds exhibited potent cytotoxicity (IC50 = 0.10-22.96 µM) against three cancer (MCF-7, A2780 and HT29) cell lines with selectivity index in the range of 1-258. Moreover, these compounds also exhibited significant anti-inflammatory activity (18.13-44.51% inhibition of inflammation) mediated by inhibition of COX-1/2 with preferential inhibition of COX-2. The study of SAR revealed favorable cytotoxic outcomes of the aliphatic side chain and 4-thiazolidinone moiety at C6 of the pyrrolizine nucleus, while anti-inflammatory activities was improved with the (hetero)aromatic substituents. The IC50 values which inhibit COX-2 were higher than those needed to inhibit the growth of cancer cell lines. Mechanistic studies also revealed inhibition of multiple kinases by compounds 12, 19 and 22. Moreover, compounds 12, 14, 16 and 22 induced cell cycle arrest and apoptosis in MCF-7 cells. Docking studies revealed nice fitting of the new compounds into COX-1/2. Additionally, compounds 12, 19 and 22 also exhibited higher affinity for CDK2 than CAN508. To sum up, the above-mentioned data highlight these compounds as promising anti-inflammatory and anticancer agents.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos/farmacologia , Inibidores de Ciclo-Oxigenase/farmacologia , Desenho de Drogas , Edema/tratamento farmacológico , Pirrolidinas/farmacologia , Tiazolidinas/farmacologia , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase/síntese química , Inibidores de Ciclo-Oxigenase/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Células HT29 , Humanos , Células MCF-7 , Masculino , Estrutura Molecular , Pirrolidinas/síntese química , Pirrolidinas/química , Ratos , Bases de Schiff/síntese química , Bases de Schiff/química , Bases de Schiff/farmacologia , Relação Estrutura-Atividade , Tiazolidinas/química
2.
Molecules ; 24(20)2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31640238

RESUMO

The current study was chiefly designed to examine the antiproliferative and antioxidant activities of some novel quinazolinone(thione) derivatives 6-14. The present work focused on two main points; firstly, comparing between quinazolinone and quinazolinthione derivatives. Whereas, antiproliferative (against two cell lines namely, HepG2 and MCF-7) and antioxidant (by two methods; ABTS and DPPH) activities of the investigated compounds, the best quinazolinthione derivatives were 6 and 14, which exhibited excellent potencies comparable to quinazolinone derivatives 5 and 9, respectively. Secondly, we compared the activity of four series of Schiff bases which included the quinazolinone moiety (11a-d). In addition, the antiproliferative and antioxidant activities of the compounds with various aryl aldehyde hydrazone derivatives (11a-d) analogs were studied. The compounds exhibited potency that increased with increasing electron donating group in p-position (OH > OMe > Cl) due to extended conjugated systems. Noteworthy, most of antiproliferative and antioxidant activities results for the tested compounds are consistent with the DFT calculations.


Assuntos
Antineoplásicos/síntese química , Antioxidantes/síntese química , Quinazolinonas/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Proliferação de Células/efeitos dos fármacos , Teoria da Densidade Funcional , Ensaios de Seleção de Medicamentos Antitumorais , Células Hep G2 , Humanos , Hidrazonas/síntese química , Hidrazonas/química , Hidrazonas/farmacologia , Células MCF-7 , Estrutura Molecular , Quinazolinonas/química , Quinazolinonas/farmacologia , Bases de Schiff/síntese química , Bases de Schiff/química , Bases de Schiff/farmacologia , Relação Estrutura-Atividade , Tionas/química
3.
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
4.
Molecules ; 24(17)2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31480486

RESUMO

Elucidation of the structure and function of biomolecules provides us knowledge that can be transferred into the generation of new materials and eventually applications in e.g., catalysis or bioassays. The main problems, however, concern the complexity of the natural systems and their limited availability, which necessitates utilization of simple biomimetic analogues that are, to a certain degree, similar in terms of structure and thus behaviour. We have, therefore, devised a small library of six tridentate N-heterocyclic coordinating agents (L1-L6), which, upon complexation, form two groups of artificial, monometallic non-heme iron species. Utilization of iron(III) chloride leads to the formation of the 1:1 (Fe:Ln) 'open' complexes, whereas iron(II) trifluoromethanosulfonate allows for the synthesis of 1:2 (M:Ln) 'closed' systems. The structural differences between the individual complexes are a result of the information encoded within the metallic centre and the chosen counterion, whereas the organic scaffold influences the observed properties. Indeed, the number and nature of the external hydrogen bond donors coming from the presence of (benz)imidazole moieties in the ligand framework are responsible for the observed biological behaviour in terms of mimicking phenoxazinone synthase activity and interaction with DNA.


Assuntos
Benzimidazóis/química , Materiais Biomiméticos/química , DNA/metabolismo , Ferro/química , Oxirredutases/metabolismo , Bases de Schiff/química , Aminofenóis/metabolismo , Animais , Ligação Competitiva , Catálise , Bovinos , Fluorescência , Imidazóis , Cinética , Ligantes , Oxazinas , Oxirredução , Bases de Schiff/síntese química , Elementos de Transição/metabolismo
5.
Molecules ; 24(18)2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31487951

RESUMO

To obtain highly selective toxic derivatives of fipronil, a series of Schiff bases with an alkynyl group (3a-3k) were designed and synthesized from 4-ethynylbenzaldehyde (2) and 4-substituted 5-amino-N-arylpyrazole (1a-1k) via a nucleophilic addition elimination reaction in ionic liquids. Utilization of ionic liquids was demonstrated to endow the yield of each compound beyond 50%, which was enhanced over 1.5 times of the synthetic productive rates comparing the conventional method by which longer reactive time was consumed. The derivatives were characterized via nuclear magnetic resonance hydrogen spectroscopy (1H-NMR), carbon-13 nuclear magnetic resonance spectroscopy (13C-NMR), and electrospray ionization high resolution mass spectrometry (ESI-HRMS). The cytotoxicity of these derivatives on Trichoplusia ni (Hi-5) cell and Spodoptera litura cell (SL cell) was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) bioassays. The results indicated that several compounds had potential cytotoxicity on Hi-5 cell, especially a 4-ethyl substituted alkynyl Schiff base derivative (3f) that was demonstrated to possess high selective toxicity to the Hi-5 cell than the SL cell. In addition, 3f exhibited comparable toxic activity to commercial fipronil on a Hi-5 cell while a little toxic effect on the SL cell, which satisfied the expectation for selective toxicity screening.


Assuntos
Líquidos Iônicos/química , Pirazóis/síntese química , Pirazóis/farmacologia , Bases de Schiff/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Química Sintética , Humanos , Estrutura Molecular , Bases de Schiff/síntese química
6.
Analyst ; 144(17): 5254-5260, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31364615

RESUMO

In this paper we report a novel probe based on a luminescent 23-membered [1 + 1] Schiff-base macrocyclic mononuclear Sm(iii) complex Sm-2e, originating from the dialdehyde H2Qe and 1,2-bis(2-aminoethoxy)ethane precursors, which is synthesized by the Sm(iii) ion template method. X-ray structural analyses confirm that each ten-coordinate Sm(iii) center with the coordination geometry of a distorted bicapped square antiprism is fully encapsulated by a flexible macrocyclic ligand H2L2e to form a "lasso-type" architecture, and this architecture could enable efficient energy transfer in various solvents confirmed by long lifetimes (33.5-65.2 µs) and high quantum yields (0.23-0.76%) of the Sm(iii) ion. Simultaneously, complex Sm-2e could serve as a probe for sensing organic solvents. Particularly, this complex probe Sm-2e exhibits a highly selective, rapid and sensitive response to tetrahydrofuran (THF), which is easily distinguished by a large absorption shift, even visible to the naked eye, and complete fluorescence quenching. Moreover, the limit of detection for THF is about 0.20% determined by titration experiments, and good selectivity for THF could still be realized in mixture solvents. Consequently, this colorimetric and "turn off" fluorescent probe Sm-2e could be a valuable candidate as a sensor material for sensing THF which has been rarely reported.


Assuntos
Complexos de Coordenação/química , Corantes Fluorescentes/química , Furanos/análise , Colorimetria/métodos , Complexos de Coordenação/síntese química , Fluorescência , Corantes Fluorescentes/síntese química , Limite de Detecção , Samário/química , Bases de Schiff/síntese química , Bases de Schiff/química , Espectrometria de Fluorescência/métodos
7.
Molecules ; 24(17)2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31466322

RESUMO

A series of Schiff bases 14-25 were designed and synthesized for evaluation of their antibacterial properties against multi-drug resistant bacteria (MDRB). The antibacterial activities of Schiff bases 14-25 showed that most of the synthesized compounds displayed a significant antibacterial activity. Assessment of in silico ADMET properties (absorption, distribution, metabolism, excretion and toxicity) of Schiff bases illustrates that all derivatives showed agreement to the Lipinski's rule of five. Further enzymatic assay aided by molecular docking study demonstrated that compound 18 is a potent inhibitor of staphylococcus aureus DNA gyrase and dihydrofolate reductase kinases. This study could be valuable in the discovery of new potent antimicrobial agents.


Assuntos
Antibacterianos/síntese química , Pirazóis/química , Bases de Schiff/síntese química , Staphylococcus aureus/enzimologia , Antibacterianos/química , Antibacterianos/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Simulação por Computador , DNA Girase/metabolismo , Antagonistas do Ácido Fólico/síntese química , Antagonistas do Ácido Fólico/química , Antagonistas do Ácido Fólico/farmacologia , Modelos Moleculares , Simulação de Acoplamento Molecular , Estrutura Molecular , Bases de Schiff/química , Bases de Schiff/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Tetra-Hidrofolato Desidrogenase/metabolismo , Inibidores da Topoisomerase II/síntese química , Inibidores da Topoisomerase II/química , Inibidores da Topoisomerase II/farmacologia
8.
Talanta ; 205: 120118, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31450418

RESUMO

The semi-metallic element gallium has repeatedly shown bio-activities in preclinical and clinical studies. Gallium derivatives have already entered clinical trials for treatment of various refractory malignancies. To better monitor or track the status of administered gallium compound, herein a novel fluorescent probe N,N',N'',N'''-Tetrakis(2-hydroxybenzylidene)biphenyl-3,3',4,4'-tetramine (bis-salophen) has been designed and synthesized. The bis-salophen probe was found to recognize gallium ions (Ga3+) with high selectivity and sensitivity over other cations via fluorescence "turn on" strategy. The spectroscopy results exhibited a 1:2 stoichiometry for probe and Ga3+, and the association constant and limit of detection were calculated as 8.85 × 106 M-1 and 13.0 nM, respectively. Additionally, base on spectroscopy and theoretical research, the mechanism of Ga3+ sensing action was explored by density functional theory (DFT), which indicated suppression of photoinduced electron transfer (PET) action along with the interruption of π-conjugation between salicylaldehyde and 3,3-diaminobenzidine backbone by Ga3+ ions. Furthermore, the biological applicability of bis-salophen probe were evaluated in various normal and cancer cell lines, results have shown that this probe is highly selective and sensitive for cancer cells. Finally, zebrafish imaging confirmed and indicated that the probe is also capable of examining Ga3+ ions. Collectively, these results suggest that we have successfully developed a novel probe for selective and sensitive detection of Ga3+ ions both in living cells and zebrafish. We expect that our work here will shed light on future development of Ga3+ detecting probes and wider application in the filed of biology and medicine shall be anticipated.


Assuntos
Quelantes/química , Corantes Fluorescentes/química , Gálio/análise , 3,3'-Diaminobenzidina/análogos & derivados , 3,3'-Diaminobenzidina/síntese química , 3,3'-Diaminobenzidina/efeitos da radiação , Animais , Linhagem Celular Tumoral , Quelantes/síntese química , Quelantes/efeitos da radiação , Teoria da Densidade Funcional , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/efeitos da radiação , Humanos , Microscopia de Fluorescência/métodos , Modelos Químicos , Bases de Schiff/síntese química , Bases de Schiff/química , Bases de Schiff/efeitos da radiação , Raios Ultravioleta , Peixe-Zebra
9.
Analyst ; 144(19): 5706-5716, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31436770

RESUMO

A novel Schiff base fluorescence probe (HL) was synthesized by the condensation of salicylaldehyde and an 8-aminoquinoline derivative. This probe acts as a "turn-on" dual selectivity fluorescence probe for Zn2+ and Al3+ ions, providing different colors and detection limits (DL) of 11.5 and 23.5 nM, respectively. Moreover, when Zn2+ and Al3+ co-exist, HL exhibits a preference for Al3+ by displacing Zn2+ from the HL-Zn2+ complex, realizing a dual-channel signal output for Al3+. The HL-Al3+ system could further discern F- by a "turn-off" fluorescence response with a DL of 86.0 nM. Furthermore, the probe HL was capable of monitoring intracellular Al3+, Zn2+ and F- in living PC12 cells in vitro through fluorescence imaging, which proved its value in potential in vivo applications.


Assuntos
Alumínio/análise , Corantes Fluorescentes/química , Fluoretos/análise , Zinco/análise , Aminoquinolinas/síntese química , Aminoquinolinas/química , Aminoquinolinas/toxicidade , Animais , Colorimetria/métodos , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/toxicidade , Limite de Detecção , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Células PC12 , Ratos , Bases de Schiff/síntese química , Bases de Schiff/química , Bases de Schiff/toxicidade , Espectrometria de Fluorescência/métodos
10.
Arch Pharm (Weinheim) ; 352(8): e1900034, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31330079

RESUMO

A series of new Schiff bases bearing 1,2,3-triazole 12a-o was designed, synthesized, and evaluated as α-glucosidase inhibitors. All the synthesized compounds showed promising inhibition against α-glucosidase and were more potent than the standard drug acarbose. The kinetic study on the most potent compound 12n showed that this compound acted as a competitive α-glucosidase inhibitor. The docking study revealed that the synthesized compounds interacted with the important residues in the active site of α-glucosidase.


Assuntos
Desenho de Drogas , Inibidores de Glicosídeo Hidrolases/farmacologia , Simulação de Acoplamento Molecular , Triazóis/farmacologia , alfa-Glucosidases/metabolismo , Relação Dose-Resposta a Droga , Inibidores de Glicosídeo Hidrolases/síntese química , Inibidores de Glicosídeo Hidrolases/química , Humanos , Estrutura Molecular , Bases de Schiff/síntese química , Bases de Schiff/química , Bases de Schiff/farmacologia , Relação Estrutura-Atividade , Triazóis/síntese química , Triazóis/química
11.
Dalton Trans ; 48(33): 12496-12511, 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31361288

RESUMO

Three tetranuclear (1-3) complexes and a mononuclear (4) palladium(ii) complex were synthesized from 3-acetyl-chromen-2-one Schiff base ligands [H2-3MAC-Rtsc] (where R = H [H2-3MAC-tsc]; CH3[H2-3MAC-mtsc]; C2H5[H2-3MAC-etsc] or C6H5[H2-3MAC-ptsc]) and potassium tetrachloropalladate. Their formation was confirmed by spectroscopic techniques and X-ray crystallographic analysis. Their ability to bind with DNA and albumin was analysed by using absorption and emission titrations. The MTT assay was carried out to analyze the anticancer potential of the ligands and synthesized complexes against HepG2 (human liver cancer) and HT-29 (human colon cancer) cells. In addition, the compounds were less toxic when tested against the human normal keratinocyte cells (HaCaT). Ligands and complexes displayed better cytotoxicity with lower IC50 values than the standard drug cisplatin. Further AO-EB and DAPI staining assays were carried out to detect the mode of cell death induced by the complexes i.e. apoptosis or necrosis. The complex 3 showed better cytotoxicity and was further subjected to flow cytometric analysis. The results suggested that the complex 3 induced apoptotic cell death.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Cromonas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Cromonas/química , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HT29 , Células Hep G2 , Humanos , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Ligantes , Modelos Moleculares , Estrutura Molecular , Imagem Óptica , Bases de Schiff/síntese química , Bases de Schiff/química , Bases de Schiff/farmacologia , Relação Estrutura-Atividade
12.
Molecules ; 24(15)2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31344947

RESUMO

Our main interest is the characterization of compounds to support the development of alternatives to currently marketed drugs that are losing effectiveness due to the development of resistance. Schiff bases are promising biologically interesting compounds having a wide range of pharmaceutical properties, including anti-inflammatory, antipyretic, and antimicrobial activities, among others. In this work, we have synthesized 12 Schiff base derivatives of 4-aminoantipyrine. In vitro antimicrobial, antioxidant, and cytotoxicity properties are analyzed, as well as in silico predictive adsorption, distribution, metabolism, and excretion (ADME) and bioactivity scores. Results identify two potential Schiff bases: one effective against E. faecalis and the other with antioxidant activity. Both have reasonable ADME scores and provides a scaffold for developing more effective compounds in the future. Initial studies are usually limited to laboratory in vitro approaches, and following these initial studies, much research is needed before a drug can reach the clinic. Nevertheless, these laboratory approaches are mandatory and constitute a first filter to discriminate among potential drug candidates and chemical compounds that should be discarded.


Assuntos
Ampirona/farmacologia , Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Antiprotozoários/farmacologia , Bases de Schiff/farmacologia , Ampirona/síntese química , Ampirona/química , Animais , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Antioxidantes/síntese química , Antioxidantes/química , Antiprotozoários/síntese química , Antiprotozoários/química , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/farmacologia , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Bases de Schiff/síntese química , Bases de Schiff/química , Relação Estrutura-Atividade
13.
Chem Commun (Camb) ; 55(65): 9681-9684, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31347618

RESUMO

Here, we report a convenient, fast labeling strategy for the imaging of cell surface sialic acids (SAs, nine-carbon monosaccharides located at the terminals of cell surface sugar chains). This strategy is based on the synthesis of sticky, furry and fluorescent "wool-balls", which are wound into nanoclusters from p-benzoquinone/ethylenediamine polymer "wires". With abundant amino groups at the surface, the wool-balls can easily stick to the C-7 aldehyde group generated at the ends of periodate treated SAs in less than 30 min.


Assuntos
Benzoquinonas/química , Etilenodiaminas/química , Corantes Fluorescentes/química , Nanopartículas/química , Polímeros/química , Ácidos Siálicos/análise , Animais , Benzoquinonas/síntese química , Linhagem Celular Tumoral , Etilenodiaminas/síntese química , Fluorescência , Humanos , Camundongos , Microscopia de Fluorescência/métodos , Neuraminidase/química , Tamanho da Partícula , Polímeros/síntese química , Células RAW 264.7 , Bases de Schiff/síntese química , Bases de Schiff/química , Ácidos Siálicos/química
14.
Org Biomol Chem ; 17(25): 6229-6250, 2019 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-31183482

RESUMO

Tautomerism plays a pivotal role in structural stabilization and reactivity. Herein we investigate in detail, aided by DFT simulations, the case of gossypol, a naturally occurring atropisomeric dialdehyde showing promising properties as a male contraceptive and an antineoplasic agent. Its toxicity linked to reactive aldehydo groups can be reduced through amino conjugation. The occurrence of either imino or enamino structures is puzzling indeed and a clear-cut rationale is missing yet. N-enamine-N-enamine structures are prevalent or exclusive tautomers for Schiff bases from gossypol, while their corresponding hydrazones only possess N-imine-N-imine structures both in solution and the solid state. The modification of interactions between the lone pairs on the nitrogen atoms by altering the steric hindrance of the non-iminic nitrogen can favor enamine tautomers. This assumption has now been confirmed and, in the solid state, hydrazones from N-aminopiperidine and their cis-2,6-dimethylderivative present bis-imine and bis-enamine structures, respectively. In solution, these compounds exist in equilibrium between both structures. The tautomerization mechanism, analysis of axial chirality and aromaticity in such H-bonded pseudorings are discussed as well.


Assuntos
Gossipol/análogos & derivados , Gossipol/síntese química , Hidrazonas/síntese química , Piperidinas/química , Bases de Schiff/síntese química , Teoria da Densidade Funcional , Ligações de Hidrogênio , Isomerismo , Modelos Químicos , Conformação Molecular , Piperidinas/síntese química
15.
Chem Commun (Camb) ; 55(54): 7852-7855, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31215553
16.
Eur J Med Chem ; 178: 214-231, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31185412

RESUMO

Discovery of antimicrobial agents with a novel model of action is in urgent need for the clinical management of multidrug-resistant bacterial infections. Recently, we reported the identification of a first-in-class bacterial ribosomal RNA synthesis inhibitor, which interrupted the interaction between the bacterial transcription factor NusB and NusE. In this study, a series of diaryl derivatives were rationally designed and synthesized based on the previously established pharmacophore model. Inhibitory activity against the NusB-NusE binding, circular dichroism of compound treated NusB, antimicrobial activity, cytotoxicity, hemolytic property and cell permeability using Caco-2 cells were measured. Structure-activity relationship and quantitative structure-activity relationship were also concluded and discussed. Some of the derivatives demonstrated improved antimicrobial activity than the hit compound against a panel of clinically important pathogens, lowering the minimum inhibition concentration to 1-2 µg/mL against Staphylococcus aureus, including clinical strains of methicillin-resistant Staphylococcus aureus at a level comparable to some of the marketed antibiotics. Given the improved antimicrobial activity, specific inhibition of target protein-protein interaction and promising pharmacokinetic properties without significant cytotoxicity, this series of diaryl compounds have high potentials and deserve for further studies towards a new class of antimicrobial agents in the future.


Assuntos
Compostos de Anilina/farmacologia , Antibacterianos/farmacologia , Benzilaminas/farmacologia , Ligação Proteica/efeitos dos fármacos , Bases de Schiff/farmacologia , Compostos de Anilina/síntese química , Compostos de Anilina/química , Compostos de Anilina/toxicidade , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/toxicidade , Proteínas de Bactérias/metabolismo , Benzilaminas/síntese química , Benzilaminas/química , Benzilaminas/toxicidade , Células CACO-2 , Desenho de Drogas , Eritrócitos/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Células HeLa , Hemólise/efeitos dos fármacos , Humanos , Queratinócitos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Bases de Schiff/síntese química , Bases de Schiff/química , Bases de Schiff/toxicidade , Relação Estrutura-Atividade , Fatores de Transcrição/metabolismo
17.
Carbohydr Polym ; 220: 1-11, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31196526

RESUMO

Chitosans are versatile biopolymers recognized for their wide range of biological activities. However, the low solubility in neutral and basic solutions restricts the applications. Thus amphiphilic biopolymeric Schiff bases from chitosans, salicylaldehyde and glycidol were successfully synthesized and characterized using 1H-NMR, UV/Vis, FTIR, TG/DTG-DTA and tested for their antimicrobial activities against plant pathogenic microorganisms and human breast cancer cells (MCF-7). Overall, functionalization of chitosans with salicylaldehyde and glycidol with different molecular weight (Mw¯) was performed to improve the biological actives of chitosans. Thus the biological activity of the new amphiphilic compounds prepared in this work were evaluated regarding microorganisms with agricultural relevance and tumor cells. The biopolymeric amphiphilic Schiff bases showed significant effects against Pseudomonas syringae (IC50 < 5 µg mL-1) compared to the natural chitosans with medium Mw¯ (CHM 223 kDa) and low Mw¯ (CHL 64 kDa), which had IC50 values of 42 and 37 µg mL-1, respectively. In addition, they improved antitumor activity against tumor cells compared to the natural chitosan.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antineoplásicos/farmacologia , Quitosana , Fusarium/efeitos dos fármacos , Pseudomonas syringae/efeitos dos fármacos , Bases de Schiff , Animais , Células 3T3 BALB , Quitosana/análogos & derivados , Quitosana/química , Quitosana/farmacologia , Humanos , Células MCF-7 , Camundongos , Testes de Sensibilidade Microbiana/métodos , Peso Molecular , Bases de Schiff/síntese química , Bases de Schiff/química , Bases de Schiff/farmacologia , Solubilidade
18.
Carbohydr Polym ; 216: 113-118, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31047047

RESUMO

A controllable drug delivery system demonstrates a promising tool for diverse biomedical applications. In this work, a group of amphiphilic macromolecules was designed and prepared via Schiff base reactions between 2,3-dialdehyde cellulose (DAC) with oleylamine and amino-containing compounds. Benefiting from the self-assemble process of these amphiphilic macromolecules in the poor solvent, a group of novel pH-responsive nanoparticles (NPs) were facilely fabricated by using nanoprecipitation dropping technique. The high amount of aldehyde groups on DAC chains enabled immobilization of tunable amounts of amine compounds (up to 1.67 mmol/g) in the NPs. Furthermore, the Schiff base bonds in NPs allowed the efficient release of the drug in acidic tumor microenvironment by cleaving the Schiff base linkages. This study demonstrates the formation of a group of novel pH-sensitive and drug-loadable NPs, which provide a simple and efficient drug delivery system for the potential application for cancer treatment.


Assuntos
Aminas/química , Celulose/análogos & derivados , Preparações de Ação Retardada/química , Nanopartículas/química , Rodaminas/química , Bases de Schiff/química , Aminas/síntese química , Celulose/síntese química , Celulose/química , Preparações de Ação Retardada/síntese química , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Rodaminas/síntese química , Bases de Schiff/síntese química
19.
Carbohydr Polym ; 214: 311-316, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30926002

RESUMO

Bacterial cellulose is an attractive material due to its outstanding biocompatibility, nanometer size and high purity, but the difficulty of dispersing has restricted its wide applications. In this study, chitosan was grafted onto bacterial cellulose by Schiff base reaction, and then obtained the nano-sized fibrils by ultrasonic dispersion process. Different concentrations of NaIO4 with various time and temperature were applied, and the maximum grafting amount of chitosan was 12.38%. The obtained products were characterized by FTIR, XRD, SEM and TEM. From the dispersibility and stability behavior research, the suspension containing chitosan was more uniform and showed better acid and temperature stability. It can also be observed in SEM and TEM images that the bacterial cellulose were dispersed into single ones and the diameter of the isolated fibril was 30-80 nm.


Assuntos
Celulose/química , Quitosana/química , Nanofibras/química , Celulose/isolamento & purificação , Gluconacetobacter xylinus/química , Concentração de Íons de Hidrogênio , Oxirredução , Bases de Schiff/síntese química , Suspensões/química , Temperatura Ambiente
20.
Acta Crystallogr C Struct Chem ; 75(Pt 2): 97-106, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30720447

RESUMO

Two novel Schiff bases derived from indole and biphenyl have been designed and synthesized, namely 3-((E)-{(E)-[1-(biphenyl-4-yl)ethylidene]hydrazinylidene}methyl)-1-methyl-1H-indole (3-BEHMI) acetonitrile monosolvate, C24H21N3·CH3CN, and 3-((E)-{(E)-[1-(biphenyl-4-yl)ethylidene]hydrazinylidene}methyl)-1-methyl-1H-indole (3-BEHEI) acetonitrile monosolvate, C24H21N3·CH3CN. Their structures were characterized by elemental analysis, quadrupole time-of-flight MS, NMR and UV-Vis spectroscopy. The single-crystal packing structure of 3-BEHMI is largely dominated by C-H...π interactions and weak van der Waals interactions. The in vitro cytotoxicity of the two title compounds have been evaluated against two tumour cell lines (A549 human lung cancer and 4T1 mouse breast cancer) and two normal cell lines (MRC-5 normal lung cells and NIH 3T3 fibroblasts) by MTT assay. The results indicate that 3-BEHEI exhibits a slightly weaker antiproliferative capability (IC50 = ∼50 µM) than the previously reported similar Schiff base 3-BEHI (IC50 = ∼20 µM). This is in line with docking results. 3-BEHMI demonstrates a weak cytotoxic activity, with IC50 values around 110 µM, which disagrees with its docking results. Overall, the tested compounds manifest relevant cytotoxicities on the selected cancer cell lines and normal cell lines. The UV-Vis and fluorescence spectra were recorded and reproduced through the TD-DFT method with four types of hybrid density functionals, including B3LYP, M062X, PBE1PBE and WB97XD.


Assuntos
Compostos de Bifenilo/química , Compostos de Bifenilo/farmacologia , Proliferação de Células/efeitos dos fármacos , Bases de Schiff/química , Bases de Schiff/farmacologia , Animais , Compostos de Bifenilo/síntese química , Linhagem Celular Tumoral , Simulação por Computador , Cristalografia por Raios X , Humanos , Concentração Inibidora 50 , Camundongos , Simulação de Acoplamento Molecular , Estrutura Molecular , Células NIH 3T3 , Bases de Schiff/síntese química , Análise Espectral/métodos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA