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1.
J Colloid Interface Sci ; 674: 1058-1070, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39008942

RESUMO

Recently, the utilization of hydrogen-bonded organic frameworks (HOFs) with high crystallinity and inherent well-defined H-bonding networks in the field of proton conduction has received increasing attention, but obtaining HOFs with excellent water stability and prominent proton conductivity (σ) remains challenging. Herein, by employing functionalized terephthalic acids, 2,5-dihydroxyterephthalic acid, 2-hydroxyterephthalic acid, 2-nitro terephthalic acid, and terephthalic acid, respectively, four highly water-stable ionic HOFs (iHOFs), [(C8H5O6)(Me2NH2)]∙2H2O (iHOF 1), [(C8H5O5)(Me2NH2)] (iHOF 2), [(C8H4NO6)(Me2NH2)] (iHOF 3) and [(C8H5O4)(Me2NH2)] (iHOF 4) were efficiently prepared by a straightforward synthesis approach in DMF and H2O solutions. The alternating-current (AC) impedance testing in humid conditions revealed that all four iHOFs were temperature- and humidity-dependent σ, with the greatest value reaching 10-2 S·cm-1. As expected, the high density of free carboxylic acid groups, crystallization water, and protonated [Me2NH2]+ units offer adequate protons and hydrophilic environments for effective proton transport. Furthermore, the σ values of these iHOFs with different functional groups were compared. It was discovered that it dropped in the following order under 100 °C and 98 % relative humidity (RH): σ iHOF 1 (1.72 × 10-2 S·cm-1) > σ iHOF 2 (4.03 × 10-3 S·cm-1) > σ iHOF 3 (1.46 × 10-3 S·cm-1) > σ iHOF 4 (4.86 × 10-4 S·cm-1). Finally, we investigated the causes of the above differences and the proton transport mechanism inside the framework using crystal structure data, water contact angle tests, and activation energy values. This study provides new motivation to develop highly proton-conductive materials.

2.
Inorg Chem ; 63(9): 4233-4248, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38377313

RESUMO

Indium-based metal-organic frameworks (In-MOFs) have now become an attractive class of porous solids in materials science and electrochemistry due to their diverse structures and promising applications. In the field of proton conduction, to find more crystalline MOFs with splendid proton-conductive properties, herein, five three-dimensional isostructural In-MOFs, MIL-68-In or MIL-68-In-X (X = NH2, OH, Br, or NO2) using terephthalic acid (H2BDC) or functionalized terephthalic acids (H2BDC-X) as multifunctional linkages were efficiently fabricated. First, the outstanding structural stability of the five MOFs, including thermal and water stability, was verified by thermal analysis and powder X-ray diffraction. Subsequently, the H2O-mediated proton conductivities (σ) were fully assessed and compared. Notably, their σ evinced a significant positive correlation between the temperature or relative humidity (RH) and varied with the functional groups on the organic ligands. Impressively, their highest σ values are up to 10-3-10-4 S/cm (100 °C/98% RH) and change in this order: MIL-68-In-OH (1.72 × 10-3 S/cm) > MIL-68-In-NH2 (1.70 × 10-3 S/cm) > MIL-68-In-NO2 (4.47 × 10-4 S/cm) > MIL-68-In-Br (4.11 × 10-4 S/cm) > MIL-68-In (2.37 × 10-4 S/cm). Finally, the computed activation energy values under 98 or 68% RHs are assessed, and the related proton conduction mechanisms are speculated. Moreover, after electrochemical testing, these MOFs illustrate remarkable structural rigidity, laying a meritorious material foundation for future applications.

3.
Acta Pharm Sin B ; 13(7): 3054-3066, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37521857

RESUMO

Considering the undesirable metabolic stability of our recently identified NNRTI 5 (t1/2 = 96 min) in human liver microsomes, we directed our efforts to improve its metabolic stability by introducing a new favorable hydroxymethyl side chain to the C-5 position of pyrimidine. This strategy provided a series of novel methylol-biphenyl-diarylpyrimidines with excellent anti-HIV-1 activity. The best compound 9g was endowed with remarkably improved metabolic stability in human liver microsomes (t1/2 = 2754 min), which was about 29-fold longer than that of 5 (t1/2 = 96 min). This compound conferred picomolar inhibition of WT HIV-1 (EC50 = 0.9 nmol/L) and low nanomolar activity against five clinically drug-resistant mutant strains. It maintained particularly low cytotoxicity (CC50 = 264 µmol/L) and good selectivity (SI = 256,438). Molecular docking studies revealed that compound 9g exhibited a more stable conformation than 5 due to the newly constructed hydrogen bond of the hydroxymethyl group with E138. Also, compound 9g was characterized by good safety profiles. It displayed no apparent inhibition of CYP enzymes and hERG. The acute toxicity assay did not cause death and pathological damage in mice at a single dose of 2 g/kg. These findings paved the way for the discovery and development of new-generation anti-HIV-1 drugs.

4.
J Med Chem ; 66(7): 4755-4767, 2023 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-36996328

RESUMO

To enhance the anti-resistance efficacy of our previously reported non-nucleoside reverse transcriptase inhibitor (NNRTI) 4, a series of novel biphenyl-DAPY derivatives were developed using the fragment-hopping strategy. Most of the compounds 8a-v exhibited remarkably improved anti-HIV-1 potency. The most active compound 8r proved to be exceptionally potent against the wild-type HIV-1 (EC50 = 2.3 nM) and five mutant strains, such as K103N (EC50 = 8 nM) and E138K (EC50 = 6 nM), significantly better than 4. The new DAPY analogue was 8-fold less cytotoxic and had a 17-fold higher selectivity index (CC50 = 40.77 µM, SI > 17391) than etravirine and rilpivirine. Also, it displayed favorable pharmacokinetic properties with an oral bioavailability of 31.19% and weak sensitivity toward both CYP and hERG. No apparent acute toxicity (2 g/kg) and tissue damage occurred. These findings will further expand the possibility of successfully identifying biphenyl-DAPY analogues as highly potent, safe, and orally active NNRTIs for HIV treatment.


Assuntos
Fármacos Anti-HIV , HIV-1 , Inibidores da Transcriptase Reversa/farmacologia , Fármacos Anti-HIV/farmacologia , Relação Estrutura-Atividade , Compostos de Bifenilo/farmacologia , HIV-1/metabolismo , Transcriptase Reversa do HIV/metabolismo , Desenho de Fármacos
5.
Acta Chim Slov ; 69(4): 913-919, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36562166

RESUMO

A bis-Schiff base N,N'-ethylene-bis(3-bromosalicylaldimine) (H2L) was prepared from 3-bromosalicylaldehyde and ethane-1,2-diamine. With H2L as ligand, a new copper(II) complex [CuL] (1) and a new cobalt(III) complex [CoL(NCS)(DMF)] (2) were prepared and characterized by physico-chemical methods and single crystal X-ray analysis. X-ray analysis indicates that the Cu atom in complex 1 is in square planar coordination, and the Co atom in complex 2 is in octahedral coordination. The compounds were tested in vitro for their antibacterial activities on Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas fluorescens. Both complexes have effective activities on the bacteria.


Assuntos
Complexos de Coordenação , Cobre , Antibacterianos/farmacologia , Antibacterianos/química , Bactérias , Cobalto/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Cobre/química , Cristalografia por Raios X , Etilenos , Bases de Schiff/química
6.
Acta Chim Slov ; 67(2): 581-585, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33855569

RESUMO

A pair of new mononuclear zinc(II) complexes with hydrazone ligands 4-methoxybenzoic acid (1-pyridin-2-ylmethylidene)hydrazide (HLa) and benzoic acid (1-pyridin-2-ylethylidene)hydrazide (HLb) were prepared. They are [Zn(La)2] (1) and [Zn(Lb)2] (2). The complexes were characterized by physico-chemical methods and single crystal X-ray determination. The tridentate hydrazone ligands coordinate to the Zn atoms through the pyridine nitrogen, imino nitrogen and enolate oxygen atoms. The Zn atom in each complex is six coordinated by two hydrazone ligands, to form octahedral coordination. The complexes have effective activities against the bacteria Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas fluorescens.


Assuntos
Antibacterianos/farmacologia , Complexos de Coordenação/farmacologia , Hidrazonas/farmacologia , Antibacterianos/síntese química , Bactérias/efeitos dos fármacos , Complexos de Coordenação/síntese química , Hidrazonas/síntese química , Ligantes , Testes de Sensibilidade Microbiana , Zinco/química
7.
Acta Chim Slov ; 66(1): 168-172, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33855483

RESUMO

A centrosymmetric O-bridged polynuclear copper(II) complex, [CuL2]n, where L is the deprotonated form of the Schiff base ligand 2-hydroxy-5-methylbenzaldehyde oxime, has been prepared and characterized by IR, UV and single-crystal X-ray determination. There is a crystallographic inversion center in the complex. The Cu atom in the complex is coordinated by the phenolate oxygen, imino nitrogen and hydroxyl oxygen atoms from two Schiff base ligands, forming octahedral geometry. The complex was tested in vitro for its antibacterial activity.

8.
Curr Top Med Chem ; 17(2): 120-137, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27237326

RESUMO

Indole is a potential lead for drug design which has been found in numerous pharmaceutically important compounds due to its medicinal properties, such as anti-tumor, anti-bacterial, anti-virus and anti-inflammatory. In the last decade, interfering with microtubule polymerization, a potential orientation to cause cell cycle arrest and apoptosis has become a promising method for cancer therapy. Thus, indole-based agents capable to modulate the microtubule assembly have gained considerable interest among scientists. This review describes the synthesis, bioactivities and SARs of indole-based agents targeting tubulin polymerization during the past decade.


Assuntos
Proliferação de Células/efeitos dos fármacos , Indóis/farmacologia , Tubulina (Proteína)/química , Humanos , Polimerização
9.
Acta Chim Slov ; 63(4): 856-863, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-28004099

RESUMO

A new trifluoromethylsulfonate salt of 2-[(3-chloropyridinium-2-yl)hydrazonomethyl]-6-methoxyphenol, (HL)CF3SO3, and its copper(II) and cobalt(III) complexes, [CuL(OH2)]CF3SO3 · 0.5H2O (1) and [CoL2]CF3SO3 · CH3OH (2), were prepared and characterized by physico-chemical methods and single crystal X-ray analysis. A trifluoromethylsulfonate anion is present in each of the compounds. The Cu atom in complex 1 is coordinated by the phenolate O, imino N and pyridine N atoms of L ligand, giving square planar geometry. The Co atom in complex 2 is coordinated by two phenolate O, two imino N and two pyridine N atoms from two L ligands, giving octahedral geometry. The three compounds were tested in vitro for their antibacterial activities.


Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Cobalto/química , Cobre/química , Ácidos Sulfônicos/síntese química , Ácidos Sulfônicos/farmacologia , Antibacterianos/química , Complexos de Coordenação/química , Cristalografia por Raios X , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Ácidos Sulfônicos/química
10.
Eur J Med Chem ; 85: 341-51, 2014 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-25105922

RESUMO

A series of 18 novel 1-indolyl acetate-5-nitroimidazole 3a-3r were designed, synthesized, and evaluated for their in vitro biological activities as potential tubulin polymerization inhibitors. Among these compounds, 3p displayed strong antitumor activity with IC50 of 2.00, 1.05, 0.87 µM against A549, Hela and U251 respectively, and also showed the most potent PLK1 inhibitory activity with IC50 of 2.4 µM. Molecular docking studies within the colchicine binding site of tubulin were in good agreement with the tubulin polymerization inhibitory data and confirmed the importance of the configuration of the synthesized 1-indolyl acetate-5-nitroimidazolefor potential tubulin polymerization inhibitors.


Assuntos
Desenho de Fármacos , Simulação de Acoplamento Molecular , Nitroimidazóis/química , Nitroimidazóis/farmacologia , Multimerização Proteica/efeitos dos fármacos , Tubulina (Proteína)/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Nitroimidazóis/síntese química , Nitroimidazóis/metabolismo , Estrutura Quaternária de Proteína , Relação Quantitativa Estrutura-Atividade , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/síntese química , Moduladores de Tubulina/química , Moduladores de Tubulina/metabolismo , Moduladores de Tubulina/farmacologia
11.
Eur J Med Chem ; 76: 387-96, 2014 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-24594526

RESUMO

A series of 2-Styryl-5-Nitroimidazole derivatives (25-48) have been synthesized and their biological activities were also evaluated against two Gram-negative bacterial strains: Escherichia coli and Pseudomonas aeruginosa and two Gram-positive bacterial strains: Bacillus subtilis and Bacillus thuringiensis as potential FabH inhibitors. All the compounds were structurally determined by (1)H NMR, MS, and elemental analysis. E. coli ß-ketoacyl-acyl carrier protein synthase III inhibitory assay and docking simulation indicated that compound 33 with IC50 of 9.0-36.4 µg/mL and compound 47 with IC50 of 6.3-34.3 µg/mL against bacterial strains were most potent inhibitors of E. coli FabH. And more, compounds 33 and 47 which possessed a broad-spectrum of antibacterial activities didn't exhibit any toxicity towards macrophage.


Assuntos
Acetiltransferases/antagonistas & inibidores , Antibacterianos/química , Antibacterianos/farmacologia , Proteínas de Escherichia coli/antagonistas & inibidores , Nitroimidazóis/química , Nitroimidazóis/farmacologia , Estireno/química , 3-Oxoacil-(Proteína de Transporte de Acila) Sintase , Antibacterianos/síntese química , Cristalografia por Raios X , Ácido Graxo Sintase Tipo II/antagonistas & inibidores , Testes de Sensibilidade Microbiana , Nitroimidazóis/síntese química
12.
Curr Top Med Chem ; 13(24): 3118-30, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24200359

RESUMO

Imidazole, a five-membered heterocycle having three carbon atoms, and two double bonds, having efficient antibacterial Escherichia coli, Bacillus subtili, Bacillus proteus, Staphylococcus aureus, Pseudomonas aeruginosa, and Helicobacter pyloriurease etc, shows a broad-spectrum of antibacterial activities. To Search new antibacterial drugs to overcome resistance of microorganisms to antibiotics, to date hundreds of this sort of derivatives have been synthesized and possess potent antibacterial activity. As the structure of imidazole derivatives is various, the target of antibacterial is also diverse including ß-Lactamases, ß-ketoacyl-acyl carrier protein synthase III (FabH), DNA gyrase and topoisomerase, glutamate racemase and urease. In this review, we will discuss the emergence of resistance to antibiotics and attempt to summarize the main developments of imidazole derivatives in the past ten years. We hope that increasing knowledge of the structure-activity relationship (SAR) will be beneficial to the rational design of new generation of small molecule antibacterial drugs.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Imidazóis/química , 3-Oxoacil-(Proteína de Transporte de Acila) Sintase , Acetiltransferases/antagonistas & inibidores , Isomerases de Aminoácido/antagonistas & inibidores , DNA Girase/metabolismo , DNA Topoisomerase IV/antagonistas & inibidores , Desenho de Fármacos , Farmacorresistência Bacteriana Múltipla , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Proteínas de Escherichia coli/antagonistas & inibidores , Ácido Graxo Sintase Tipo II/antagonistas & inibidores , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/enzimologia , Testes de Sensibilidade Microbiana , Relação Quantitativa Estrutura-Atividade , Inibidores da Topoisomerase II/química , Inibidores da Topoisomerase II/farmacologia , Urease/antagonistas & inibidores , Inibidores de beta-Lactamases
13.
Eur J Med Chem ; 66: 1-11, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23777898

RESUMO

A series of sulfonamides containing coumarin moieties had been prepared that showed a very interesting profile for the inhibition of two human carbonic anhydrase inhibitors. These compounds were evaluated for their ability to inhibit the enzymatic activity of the physiologically dominant isozymes hCA II and the tumor-associated isozyme hCA IX. The most potent inhibitor against hCA II and IX were compounds 5d (IC50 = 23 nM) and 5l (IC50 = 24 nM), respectively. These sulfonamides containing coumarin moieties may prove interesting lead candidates to target tumor-associated CA isozymes, wherein the CA domain is located extracellularly. Eighteen compounds were scrutinized by CoMFA and CoMSIA techniques of 3D quantitative structure-activity relationship. Nine of the compounds were evaluated for cytotoxicity against human macrophage.


Assuntos
Anidrase Carbônica II/antagonistas & inibidores , Anidrase Carbônica IV/antagonistas & inibidores , Cumarínicos/química , Cumarínicos/farmacologia , Desenho de Fármacos , Relação Quantitativa Estrutura-Atividade , Sulfonamidas/química , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Anidrase Carbônica II/química , Anidrase Carbônica II/metabolismo , Anidrase Carbônica IV/química , Anidrase Carbônica IV/metabolismo , Inibidores da Anidrase Carbônica/síntese química , Inibidores da Anidrase Carbônica/química , Inibidores da Anidrase Carbônica/metabolismo , Inibidores da Anidrase Carbônica/farmacologia , Técnicas de Química Sintética , Cumarínicos/síntese química , Cumarínicos/metabolismo , Humanos , Isoenzimas/antagonistas & inibidores , Isoenzimas/química , Isoenzimas/metabolismo , Células MCF-7 , Melanoma Experimental , Simulação de Acoplamento Molecular , Conformação Proteica , Especificidade por Substrato
14.
Eur J Med Chem ; 65: 456-63, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23770447

RESUMO

A series of novel 1-(2-hydroxypropyl)-2-styryl-5-nitroimidazole derivatives had been designed, synthesized, isolated and evaluated as potentiators of antibacterial agents. All these synthesized compounds were determined by elemental analysis, (1)H NMR, and MS. Their biological activities were also evaluated against two Gram-negative bacterial strains: Escherichia coli and Pseudomonas aeruginosa and two Gram-positive bacterial strains: Bacillus thuringiensis and Bacillus subtilis by MTT method as potential FabH inhibitory. The results showed that compound 30 exhibited the most potent E. coli FabH inhibitory activity with IC50 of 4.6 µM. Molecular modeling simulation studies were performed in order to predict the biological activities of the proposed compounds. All compounds have been tested for toxicity by MTT assay on human macrophage.


Assuntos
Antibacterianos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Bacillus thuringiensis/efeitos dos fármacos , Desenho de Fármacos , Escherichia coli/efeitos dos fármacos , Nitroimidazóis/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Antibacterianos/síntese química , Antibacterianos/química , Relação Dose-Resposta a Droga , Humanos , Macrófagos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Nitroimidazóis/síntese química , Nitroimidazóis/química , Relação Estrutura-Atividade
15.
Acta Crystallogr Sect E Struct Rep Online ; 65(Pt 7): o1631-2, 2009 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-21582898

RESUMO

In the asymmetric unit of the title hydrazone compound, C(15)H(10)Br(2)N(2)O(4), there are two independent mol-ecules. In each mol-ecule, the five-membered ring adopts a flattened envelope conformation; the flap atoms are displaced by 0.114 (2) and 0.219 (2) Šfrom the planes of the other four atoms. In one mol-ecule the dihedral angle between the two benzene rings is 22.8 (2)°, while in the other it is 40.8 (2)°. Each mol-ecule displays an E configuration with respect to the C=N bond. In both mol-ecules, intra-molecular O-H⋯N hydrogen bonds are observed. In the crystal structure, mol-ecules are linked through inter-molecular N-H⋯O hydrogen bonds, forming chains along the a axis.

16.
Acta Crystallogr Sect E Struct Rep Online ; 65(Pt 7): o1636, 2009 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-21582901

RESUMO

In the title mol-ecule, C(16)H(13)BrN(2)O(4), the two benzene rings form a dihedral angle of 74.9 (2)°. In the crystal, mol-ecules are linked via inter-molecular N-H⋯O hydrogen bonds into chains propagating along the c axis.

17.
Acta Crystallogr Sect E Struct Rep Online ; 65(Pt 7): o1649, 2009 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-21582913

RESUMO

The title hydrazone compound, C(16)H(15)BrN(2)O(3), adopts an E configuration about the C=N double bond. The mol-ecule is twisted, the dihedral angle between the two substituted benzene rings being 22.0 (2)°. In the crystal structure, mol-ecules are linked through inter-molecular N-H⋯O hydrogen bonds, forming chains along the c axis.

18.
Acta Crystallogr Sect E Struct Rep Online ; 65(Pt 7): o1650, 2009 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-21582914

RESUMO

In the title hydrazone compound, C(15)H(13)BrN(2)O(3)·CH(3)OH, the methanol solvate is linked to the benzohydrazide molecule through O-H⋯N and O-H⋯O hydrogen bonds. The benzohydrazide mol-ecule adopts an E configuration about the C=N double bond. The mol-ecule is twisted, with a dihedral angle between the two substituted benzene rings of 35.7 (2)°. In the crystal structure, mol-ecules are linked through inter-molecular N-H⋯O and O-H⋯O hydrogen bonds, forming layers parallel to the ac plane.

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