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1.
Molecules ; 26(16)2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34443460

RESUMO

Synthetic heterocyclic compounds have incredible potential against different diseases; pyridines, phenolic compounds and the derivatives of azo moiety have shown excellent antimicrobial, antiviral, antidiabetic, anti-melanogenic, anti-ulcer, anticancer, anti-mycobacterial, anti-inflammatory, DNA binding and chemosensing activities. In the present review, the above-mentioned activities of the nitrogen-containing heterocyclic compounds (pyridines), hydroxyl (phenols) and azo derivatives are discussed with reference to the minimum inhibitory concentration and structure-activity relationship, which clearly indicate that the presence of nitrogen in the phenyl ring; in addition, the hydroxyl substituent and the incorporation of a diazo group is crucial for the improved efficacies of the compounds in probing different diseases. The comparison was made with the reported drugs and new synthetic derivatives that showed recent therapeutic perspectives made in the last five years.


Assuntos
Compostos Azo/uso terapêutico , Fenóis/uso terapêutico , Piridinas/uso terapêutico , Compostos Azo/síntese química , Compostos Azo/química , Imageamento Tridimensional , Fenóis/síntese química , Fenóis/química , Piridinas/síntese química , Piridinas/química
2.
J Enzyme Inhib Med Chem ; 36(1): 1632-1645, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34289751

RESUMO

Nonsteroidal aromatase inhibitors (NSAIs) are well-established drugs for the therapy of breast cancer. However, they display some serious side effects, and their efficacy can be compromised by the development of chemoresistance. Previously, we have reported different indazole-based carbamates and piperidine-sulphonamides as potent aromatase inhibitors. Starting from the most promising compounds, here we have synthesised new indazole and triazole derivatives and evaluated their biological activity as potential dual agents, targeting both the aromatase and the inducible nitric oxide synthase, being this last dysregulated in breast cancer. Furthermore, selected compounds were evaluated as antiproliferative and cytotoxic agents in the MCF-7 cell line. Moreover, considering the therapeutic diversity of azole-based compounds, all the synthesized compounds were also evaluated as antifungals on different Candida strains. A docking study, as well as molecular dynamics simulation, were carried out to shed light on the binding mode of the most interesting compound into the different target enzymes catalytic sites.


Assuntos
Antifúngicos/farmacologia , Antineoplásicos/farmacologia , Inibidores da Aromatase/farmacologia , Compostos Azo/farmacologia , Neoplasias da Mama/tratamento farmacológico , Simulação de Acoplamento Molecular , Micoses/tratamento farmacológico , Antifúngicos/síntese química , Antifúngicos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Inibidores da Aromatase/síntese química , Inibidores da Aromatase/química , Compostos Azo/síntese química , Compostos Azo/química , Candida/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Células MCF-7 , Estrutura Molecular , Relação Estrutura-Atividade
3.
J Enzyme Inhib Med Chem ; 36(1): 1509-1520, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34238110

RESUMO

In the present study, a series of azo derivatives (TR-1 to TR-9) have been synthesised via the diazo-coupling approach between substituted aromatic amines with phenol or naphthol derivatives. The compounds were evaluated for their therapeutic applications against alpha-glucosidase (anti-diabetic) and pathogenic bacterial strains E. coli (gram-negative), S. aureus (gram-positive), S. aureus (gram-positive) drug-resistant strain, P. aeruginosa (gram-negative), P. aeruginosa (gram-negative) drug-resistant strain and P. vulgaris (gram-negative). The IC50 (µg/mL) of TR-1 was found to be most effective (15.70 ± 1.3 µg/mL) compared to the reference drug acarbose (21.59 ± 1.5 µg/mL), hence, it was further selected for the kinetic studies in order to illustrate the mechanism of inhibition. The enzyme inhibitory kinetics and mode of binding for the most active inhibitor (TR-1) was performed which showed that the compound is a non-competitive inhibitor and effectively inhibits the target enzyme by binding to its binuclear active site reversibly.


Assuntos
Antibacterianos/farmacologia , Compostos Azo/farmacologia , Inibidores Enzimáticos/farmacologia , Hipoglicemiantes/farmacologia , Simulação de Acoplamento Molecular , alfa-Glucosidases/metabolismo , Antibacterianos/síntese química , Antibacterianos/química , Compostos Azo/síntese química , Compostos Azo/química , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Escherichia coli/efeitos dos fármacos , Hipoglicemiantes/síntese química , Hipoglicemiantes/química , Cinética , Testes de Sensibilidade Microbiana , Estrutura Molecular , Pseudomonas aeruginosa/efeitos dos fármacos , Saccharomyces cerevisiae/enzimologia , Staphylococcus aureus/efeitos dos fármacos
4.
Chem Commun (Camb) ; 57(66): 8214-8217, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34308935

RESUMO

A light-responsive ion transport switch has been developed based on conformation-dependent azobenzene-incorporated lipophilic G-quadruplex channels, which provides a new smart approach for the selective transport of K+ ions across the lipid membrane.


Assuntos
Compostos Azo/metabolismo , Luz , Lipídeos de Membrana/metabolismo , Potássio/metabolismo , Compostos Azo/química , Quadruplex G , Transporte de Íons , Lipídeos de Membrana/química , Conformação Molecular , Potássio/química
5.
Int J Mol Sci ; 22(13)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201641

RESUMO

A new catalyst based on biosilica doped with palladium(II) chloride nanoparticles was prepared and tested for efficient degradation of methyl orange (MO) in water solution under UV light excitation. The obtained photocatalyst was characterized by X-ray diffraction, TEM and N2 adsorption/desorption isotherms. The photocatalytic degradation process was studied as a function of pH of the solution, temperature, UV irradiation time, and MO initial concentration. The possibilities of recycling and durability of the prepared photocatalysts were also tested. Products of photocatalytic degradation were identified by liquid chromatography-mass spectrometry analyses. The photocatalyst exhibited excellent photodegradation activity toward MO degradation under UV light irradiation. Rapid photocatalytic degradation was found to take place within one minute with an efficiency of 85% reaching over 98% after 75 min. The proposed mechanism of photodegradation is based on the assumption that both HO• and O2•- radicals, as strongly oxidizing species that can participate in the dye degradation reaction, are generated by the attacks of photons emitted from diatom biosilica (photonic scattering effect) under the influence of UV light excitation. The degradation efficiency significantly increases as the intensity of photons emitted from biosilica is enhanced by palladium(II) chloride nanoparticles immobilized on biosilica (synergetic photonic scattering effect).


Assuntos
Compostos Azo/química , Diatomáceas/química , Paládio/química , Poluentes Químicos da Água/química , Catálise , Concentração de Íons de Hidrogênio , Cinética , Nanopartículas Metálicas/química , Microscopia Eletrônica de Transmissão , Fotólise , Reciclagem , Espectrometria de Massas por Ionização por Electrospray , Temperatura , Raios Ultravioleta , Difração de Raios X
6.
J Phys Chem Lett ; 12(25): 5957-5962, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34157226

RESUMO

The ab initio determination of electronic excited state (ES) properties is the cornerstone of theoretical photochemistry. Yet, traditional ES methods become impractical when applied to fairly large molecules, or when used on thousands of systems. Machine learning (ML) techniques have demonstrated their accuracy at retrieving ES properties of large molecular databases at a reduced computational cost. For these applications, nonlinear algorithms tend to be specialized in targeting individual properties. Learning fundamental quantum objects potentially represents a more efficient, yet complex, alternative as a variety of molecular properties could be extracted through postprocessing. Herein, we report a general framework able to learn three fundamental objects: the hole and particle densities, as well as the transition density. We demonstrate the advantages of targeting those outputs and apply our predictions to obtain properties, including the state character and the exciton topological descriptors, for the two bands (nπ* and ππ*) of 3427 azoheteroarene photoswitches.


Assuntos
Compostos Azo/química , Corantes/química , Aprendizado de Máquina , Teoria Quântica , Modelos Moleculares , Conformação Molecular
7.
Food Chem ; 362: 130219, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34091170

RESUMO

The use of artificial colorants in food is highly regulated due to their potential to harm human health. Thus, it is crucial to detect these substances effectively to ensure conformance with industrial standards. In this work, we prepared a photomultiplier tube (PMT)-based electrochemiluminescence (ECL) sensor and a charged coupled device (CCD)-based ECL sensor and compared their merits in the detection of sunset yellow (SY) dye. The sensors used C,N quantum dot-embedded g-C3N4 nanosheets (QDs@NSs) as the ECL agent and K2S2O8 as the coreactant. SY was analyzed on the basis of amplification in the QDs@NHs-K2S2O8 ECL system. The PMT-based sensor realized ultrasensitive detection using a single electrode, especially at low concentrations of SY. A CCD-based sensor imaged the ECL phenomenon of an electrode array and provided the advantages of high throughput and time savings. Under optimized conditions, both sensors exhibited high specificity, reproducibility and stability; detection limits of 20 nM with PMT detection and 5 µM with CCD detection were determined for SY, with detection ranging over at least two decades. The practical feasibilities of these systems were confirmed by satisfactory detection of SY in real drink samples.


Assuntos
Compostos Azo/análise , Bebidas Gaseificadas/análise , Técnicas Eletroquímicas/instrumentação , Corantes de Alimentos/análise , Compostos Azo/química , Técnicas Eletroquímicas/métodos , Eletrodos , Corantes de Alimentos/química , Limite de Detecção , Medições Luminescentes/instrumentação , Medições Luminescentes/métodos , Nanoestruturas , Pontos Quânticos , Reprodutibilidade dos Testes
8.
Int J Mol Sci ; 22(10)2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34069455

RESUMO

In this work, we report solvent-induced complexation properties of a new N2S2 tetradentate bis-thiosemicarbazone ligand (H2LI), prepared by the condensation of 4-phenylthiosemicarbazide with bis-aldehyde, namely 2,2'-(ethane-1,2-diylbis(oxy)dibenzaldehyde, towards nickel(II). Using ethanol as a reaction medium allowed the isolation of a discrete mononuclear homoleptic complex [NiLI] (1), for which its crystal structure contains three independent molecules, namely 1-I, 1-II, and 1-III, in the asymmetric unit. The doubly deprotonated ligand LI in the structure of 1 is coordinated in a cis-manner through the azomethine nitrogen atoms and the thiocarbonyl sulfur atoms. The coordination geometry around metal centers in all the three crystallographically independent molecules of 1 is best described as the seesaw structure. Interestingly, using methanol as a reaction medium in the same synthesis allowed for the isolation of a discrete mononuclear homoleptic complex [Ni(LII)2] (2), where LII is a monodeprotonated ligand 2-(2-(2-(2-(dimethoxymethyl)phenoxy)ethoxy)benzylidene)-N-phenylhydrazine-1-carbothioamide (HLII). The ligand LII was formed in situ from the reaction of LI with methanol upon coordination to the metal center under synthetic conditions. In the structure of 2, two ligands LII are coordinated in a trans-manner through the azomethine nitrogen atom and the thiocarbonyl sulfur atom, also yielding a seesaw coordination geometry around the metal center. The charge and energy decomposition scheme ETS-NOCV allows for the conclusion that both structures are stabilized by a bunch of London dispersion-driven intermolecular interactions, including predominantly N-H∙∙∙S and N-H∙∙∙O hydrogen bonds in 1 and 2, respectively; they are further augmented by less typical C-H∙∙∙X (where X = S, N, O, π), CH∙∙∙HC, π∙∙∙π stacking and the most striking, attractive long-range intermolecular C-H∙∙∙Ni preagostic interactions. The latter are found to be determined by both stabilizing Coulomb forces and an exchange-correlation contribution as revealed by the IQA energy decomposition scheme. Interestingly, the analogous long-range C-H∙∙∙S interactions are characterized by a repulsive Coulomb contribution and the prevailing attractive exchange-correlation constituent. The electron density of the delocalized bonds (EDDB) method shows that the nickel(II) atom shares only ~0.8|e| due to the σ-conjugation with the adjacent in-plane atoms, demonstrating a very weak σ-metalloaromatic character.


Assuntos
Níquel/química , Tiossemicarbazonas/química , Aldeídos/química , Compostos Azo/química , Complexos de Coordenação/química , Cristalografia por Raios X/métodos , Ligação de Hidrogênio , Ligantes , Modelos Moleculares , Estrutura Molecular , Solventes/química , Tiossemicarbazonas/metabolismo
9.
Int J Biol Macromol ; 183: 2088-2099, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34097963

RESUMO

Efficient photocatalysis methods with a production of less number of toxic intermediates are extremely advantageous for water decontamination. The degradation efficiency, specific surface area, stability and porosity will be improving by wrapping of Fe2O3 using appropriate biopolymers. In this work, Fe2O3 reinforced chitosan (Fe2O3@CS) nanocomposite was fabricated using co-precipitation method. The chitosan makes available its surface for the useful generation of the nanocomposite. These wrapping of Fe2O3 on chitosan provides synergistically improved properties that could be attributed to the elevated partition efficiency and faster transfer of the photo-generated charge carriers, which was substantiated by the experimental outcomes from photoluminescence and ESR spectroscopy. The results obtained from DRS analysis entail the reduction in band gap of Fe2O3@CS (2.52 eV) as compared with 3.52 eV of Fe2O3. The results indicated that 89.2% and 94.6% were the maximum degradations correspondingly for MO and OG. The trapping investigation emphasized the involvement of OH radicals in the degradation of dyes over Fe2O3@CS composites. The five cycles of regeneration experiment recommended the superior photostability of the fabricated Fe2O3@CS composite. This work proposed a practical arrangement and subsequent influence of an advanced photocatalyst for the useful remediation dyes from contaminated water without causing any secondary pollution.


Assuntos
Compostos Azo/química , Quitosana/química , Compostos Férricos/química , Nanopartículas Magnéticas de Óxido de Ferro/química , Fotólise , Poluentes Químicos da Água/química , Poluição Química da Água , Purificação da Água , Catálise , Quitosana/análogos & derivados , Recuperação e Remediação Ambiental , Modelos Químicos , Nanocompostos , Nanofibras , Oxirredução , Fatores de Tempo
10.
Molecules ; 26(11)2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34063753

RESUMO

Azobenzenes are photochromic molecules that possess a large range of applications. Their syntheses are usually simple and fast, and their purifications can be easy to perform. Oligosaccharide is also a wide family of biopolymer constituted of linear chain of saccharides. It can be extracted from biomass, as for cellulose, being the principal constituent of plant cell wall, or it can be enzymatically produced as for cyclodextrins, having properties not far from cellulose. Combining these two materials families can afford interesting applications such as controlled drug-release systems, photochromic liquid crystals, photoresponsive films or even fluorescent indicators. This review will compile the different syntheses of azo-dyes-grafted oligosaccharides, and will show their various applications.


Assuntos
Compostos Azo/química , Oligossacarídeos/síntese química , Celulose/química , Preparações de Ação Retardada/química , Corantes Fluorescentes/química , Cristais Líquidos/química , Oligossacarídeos/química , Oligossacarídeos/isolamento & purificação
11.
Int J Biol Macromol ; 182: 1953-1965, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34062162

RESUMO

A durable and reversible acid-induced discoloration azobenzene UV-curable lignin-based waterborne polyurethane polymeric dye (EDA-ULPD) is prepared from lignin, azobenzene and pentaerythritol triacrylate(PETA) by chemical modification of waterborne polyurethane. Lignin and PETA are chemically bonded to the polyurethane chain to improve thermal stability, UV resistance and color fastness, while also endow the polymeric dye with UV curing performance, which is a green and environmentally friendly fixing way. The acid-induced discoloration property of EDA-ULPD with azobenzene chromophore side chain is comparable to those of 4-ethyl-4-2,2'-dihydroxy diethylamine azobenzene (EDA). As the pH value decreases from 7 to 1, the maximum absorption peak of EDA-ULPD from 420 nm to 530 nm, and the color change from yellow to pink due to the transformation of EDA molecular structure from diazo to hydrazone. Interestingly, when EDA-ULPD is fixed to the fabric in the way of UV curing, its printed fabric exhibits the performance of high concentration acid-induced discoloration (1 mol·L-1 HCl) due to the cross-linked structure formed by EDA-ULPD. The acid-induced discoloration property of EDA-ULPD printed fabrics also presents outstanding repetitious stability. The stimulus response printed fabric with reversible high concentration acid discoloration possesses a broad application prospect in smart textiles.


Assuntos
Ácidos/química , Compostos Azo/química , Corantes/química , Lignina/química , Polímeros/química , Poliuretanos/química , Raios Ultravioleta , Água/química , Compostos Azo/síntese química , Varredura Diferencial de Calorimetria , Cor , Corantes/síntese química , Reagentes para Ligações Cruzadas/química , Peso Molecular , Polímeros/síntese química , Espectroscopia de Prótons por Ressonância Magnética , Espectrofotometria Infravermelho , Temperatura
12.
World J Microbiol Biotechnol ; 37(6): 101, 2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-33983510

RESUMO

The effluent from the textile industry is a complex mixture of recalcitrant molecules that can harm the environment and human health. Biological treatments are usually applied for this wastewater, particularly activated sludge, due to its high efficiency, and low implementation and operation costs. However, the activated sludge microbiome is rarely well-known. In general, activated sludges are composed of Acidobacteria, Bacillus, Clostridium, Pseudomonas, Proteobacteria, and Streptococcus, in which Bacillus and Pseudomonas are highlighted for bacterial dye degradation. Consequently, the process is not carried out under optimum conditions (treatment yield). Therefore, this review aims to contextualize the potential environmental impacts of azo dye-containing wastewater from the textile industry, including toxicity, activated sludge microbiome identification, in particular using the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) as a novel, rapid and accurate strategy for the identification of activated sludge microbiome (potential to enhance treatment yield).


Assuntos
Compostos Azo/química , Bactérias/metabolismo , Águas Residuárias/química , Bactérias/classificação , Bactérias/isolamento & purificação , Biodegradação Ambiental , Humanos , Esgotos/microbiologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Indústria Têxtil , Microbiologia da Água
13.
J Phys Chem Lett ; 12(21): 5201-5207, 2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34038133

RESUMO

The phototriggered unbinding of the intrinsically disordered S-peptide from the RNase S complex is studied with the help of transient IR spectroscopy, covering a wide range of time scales from 100 ps to 10 ms. To that end, an azobenzene moiety has been linked to the S-peptide in a way that its helicity is disrupted by light, thereby initiating its complete unbinding. The full sequence of events is observed, starting from unfolding of the helical structure of the S-peptide on a 20 ns time scale while still being in the binding pocket of the S-protein, S-peptide unbinding after 300 µs, and the structural response of the S-protein after 3 ms. With regard to the S-peptide dynamics, the binding mechanism can be classified as an induced fit, while the structural response of the S-protein is better described as conformational selection.


Assuntos
Proteínas Intrinsicamente Desordenadas/metabolismo , Peptídeos/metabolismo , Ribonucleases/metabolismo , Sequência de Aminoácidos , Compostos Azo/química , Compostos Azo/efeitos da radiação , Proteínas Intrinsicamente Desordenadas/química , Cinética , Luz , Peptídeos/química , Ligação Proteica/efeitos da radiação , Conformação Proteica em alfa-Hélice , Desdobramento de Proteína/efeitos da radiação , Ribonucleases/química
14.
Methods Mol Biol ; 2318: 241-254, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34019294

RESUMO

Cellular senescence plays a role in several physiological processes including aging, embryonic development, tissue remodeling, and wound healing and is considered one of the main barriers against tumor development. Studies of normal and tumor cells both in culture and in vivo suggest that MYC plays an important role in regulating senescence, thereby contributing to tumor development. We have previously described different common methods to measure senescence in cell cultures and in tissues. Unfortunately, there is no unique marker that unambiguously defines a senescent state, and it is therefore necessary to combine measurements of several different markers in order to assure the correct identification of senescent cells. Here we describe protocols for simultaneous detection of multiple senescence markers in situ, a quantitative fluorogenic method to measure senescence-associated ß-galactosidase activity (SA-ß-gal), and a new method to detect senescent cells based on the Sudan Black B (SBB) analogue GL13, which is applicable to formalin-fixed paraffin-embedded tissues. The application of these methods in various systems will hopefully shed further light on the role of MYC in regulation of senescence, and how that impacts normal physiological processes as well as diseases and in particular cancer development.


Assuntos
Senescência Celular/fisiologia , Proteínas Proto-Oncogênicas c-myc/metabolismo , Coloração e Rotulagem/métodos , Envelhecimento , Compostos Azo/química , Biomarcadores , Células Cultivadas , Senescência Celular/genética , DNA/genética , Corantes Fluorescentes/química , Genes myc/genética , Genes myc/fisiologia , Humanos , Naftalenos/química , Proteínas Proto-Oncogênicas c-myc/genética , beta-Galactosidase/análise , beta-Galactosidase/metabolismo
15.
Int J Mol Sci ; 22(9)2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33925230

RESUMO

Cyclodextrins (CyDs) are water-soluble host molecules possessing a nanosized hydrophobic cavity. In the realm of molecular recognition, this cavity is used not only as a recognition site but also as a reaction medium, where a hydrophobic sensor recognizes a guest molecule. Based on the latter concept, we have designed a novel supramolecular sensing system composed of Zn(II)-dipicolylamine metal complex-based azobenzene (1-Zn) and 3A-amino-3A-deoxy-(2AS,3AS)-γ-cyclodextrin (3-NH2-γ-CyD) for sensing adenosine-5'-triphosphate (ATP). 1-Zn showed redshifts in the UV-Vis spectra and induced circular dichroism (ICD) only when both ATP and 3-NH2-γ-CyD were present. Calculations of equilibrium constants indicated that the amino group of 3-NH2-γ-CyD was involved in the formation of supramolecular 1-Zn/3-NH2-γ-CyD/ATP. The Job plot of the ICD spectral response revealed that the stoichiometry of 1-Zn/3-NH2-γ-CyD/ATP was 2:1:1. The pH effect was examined and 1-Zn/3-NH2-γ-CyD/ATP was most stable in the neutral condition. The NOESY spectrum suggested the localization of 1-Zn in the 3-NH2-γ-CyD cavity. Based on the obtained results, the metal coordination interaction of 1-Zn and the electrostatic interaction of 3-NH2-γ-CyD were found to take place for ATP recognition. The "reaction medium approach" enabled us to develop a supramolecular sensing system that undergoes multi-point interactions in water. This study is the first step in the design of a selective sensing system based on a good understanding of supramolecular structures.


Assuntos
Compostos Azo/química , Ciclodextrinas/química , gama-Ciclodextrinas/química , Trifosfato de Adenosina , Aminas/química , Dicroísmo Circular , Interações Hidrofóbicas e Hidrofílicas , Espectroscopia de Ressonância Magnética/métodos , Modelos Moleculares , Ácidos Picolínicos/química , Solubilidade , Água/química , Zinco , beta-Ciclodextrinas
16.
Parasitol Res ; 120(6): 2087-2094, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33864105

RESUMO

Control and treatment of onchocerciasis, a devastating tropical filarial disease caused by Onchocerca volvulus, rely solely on the community directed treatment with ivermectin. However, ivermectin is only microfilaricidal with evidence of resistance of the parasite among other limitations, which necessitate the search for new efficacious and safe filaricides. Ten synthetic thienylazoryl dyes were screened in vitro against adult and microfilariae worm stages of Onchocerca ochengi based on worm motility and MTT formazan assay. Cytotoxicity of active compounds was assessed on monkey kidney epithelial cells (LLC-MK2) using the MTT formazan assay. Seven (7) compounds showed both macrofilaricidal activity against adult male worms and microfilaricidal activity among which three 4a, 4c and 4e recorded the highest activity (IC50 = 4.2 to 8.8µM) against adult male worms, comparable to some standard anthelmintics. Five compounds showed rapid activity against microfilariae with 100% inhibition after 24-h incubation. The active compounds were nontoxic on monkey kidney cells (CC50> 4µg/mL), but their selectivity index values were relatively low (≤ 3). The thienylazoaryls with both macrofilaricidal and microfilaricidal activities may yield molecules which could be used for eradication of onchocerciasis following further medicinal chemistry modification of their structures to enhance their selectivity.


Assuntos
Compostos Azo/farmacologia , Filaricidas/farmacologia , Microfilárias/efeitos dos fármacos , Onchocerca/efeitos dos fármacos , Tiofenos/farmacologia , Animais , Compostos Azo/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Concentração Inibidora 50 , Masculino , Tiofenos/química
17.
Int J Mol Sci ; 22(8)2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33919771

RESUMO

Photoinduced structural changes in peptides can dynamically control the formation and dissociation of supramolecular peptide materials. However, the existence of photoresponsive viral capsids in nature remains unknown. In this study, we constructed an artificial viral capsid possessing a photochromic azobenzene moiety on the peptide backbone. An azobenzene-containing ß-annulus peptide derived from the tomato bushy stunt virus was prepared through solid-phase synthesis using Fmoc-3-[(3-aminomethyl)-phenylazo]phenylacetic acid. The azobenzene-containing ß-annulus (ß-Annulus-Azo) peptide showed a reversible trans/cis isomerization property. The ß-annulus-azo peptide self-assembled at 25 µM into capsids with the diameters of 30-50 nm before UV irradiation (trans-form rich), whereas micrometer-sized aggregates were formed after UV irradiation (cis-form rich). The artificial viral capsid possessing azobenzene facilitated the encapsulation of fluorescent-labeled dextrans and their photoinduced release from the capsid.


Assuntos
Compostos Azo/química , Capsídeo/química , Luz , Peptídeos/química , Sequência de Aminoácidos , Difusão Dinâmica da Luz , Isomerismo , Técnicas de Síntese em Fase Sólida , Espectrofotometria Ultravioleta , Fatores de Tempo
18.
Int J Mol Sci ; 22(6)2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33802075

RESUMO

The high biological activity of the chromene compounds coupled with the intriguing optical features of azo chromophores prompted our desire to construct novel derivatives of chromene incorporating azo moieties 4a-l, which have been prepared via a three-component reaction of 1-naphthalenol-4-[(4-ethoxyphenyl) azo], 1, with the benzaldehyde derivatives and malononitrile. The structural identities of the azo-chromene 4a-l were confirmed on the basis of their spectral data and elemental analysis, and a UV-visible study was performed in a Dimethylformamide (DMF) solution for these molecules. Additionally, the antimicrobial activity was investigated against four human pathogens (Gram-positive and Gram-negative bacteria) and four fungi, employing an agar well diffusion method, with their minimum inhibitory concentrations being reported. Molecules 4a, 4g, and 4h were discovered to be more efficacious against Syncephalastrum racemosum (RCMB 05922) in comparison to the reference drugs, while compounds 4b and 4h demonstrated the highest inhibitory activity against Escherichia coli (E. coli) in evaluation against the reference drugs. Moreover, their cytotoxicity was assessed against three different human cell lines, including human colon carcinoma (HCT-116), human hepatocellular carcinoma (HepG-2), and human breast adenocarcinoma (MCF-7) with a selection of molecules illustrating potency against the HCT-116 and MCF-7 cell lines. Furthermore, the molecular modeling results depicted the binding interactions of the synthesized compounds 3b and 3h in the active site of the E. coli DNA gyrase B enzyme with a clear SAR (structure-activity relationship) analysis. Lastly, the density functional theory's (DFTs) theoretical calculations were performed to quantify the energy levels of the Frontier Molecular Orbitals (FMOs) and their energy gaps, dipole moments, and molecular electrostatic potentials. These data were utilized in the chemical descriptor estimations to confirm the biological activity.


Assuntos
Anti-Infecciosos , Antineoplásicos , Compostos Azo , Benzopiranos , Proliferação de Células/efeitos dos fármacos , Simulação por Computador , Escherichia coli/crescimento & desenvolvimento , Mucorales/crescimento & desenvolvimento , Neoplasias/tratamento farmacológico , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Compostos Azo/síntese química , Compostos Azo/química , Compostos Azo/farmacologia , Benzopiranos/síntese química , Benzopiranos/química , Benzopiranos/farmacologia , Células HCT116 , Células Hep G2 , Humanos , Células MCF-7 , Neoplasias/metabolismo , Neoplasias/patologia
19.
Org Lett ; 23(8): 3110-3114, 2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33818092

RESUMO

α-Aryl-α-diazoamides were synthesized in two steps under mild conditions. This expeditious route employs Pd-catalyzed C-H arylation of N-succinimidyl 2-diazoacetate to obtain N-succinimidyl 2-aryl-2-diazoacetates, followed by aminolysis. The ensuing diazo compounds can esterify carboxyl groups in aqueous solution, and the ester products are substrates for an esterase. The broad scope of the synthetic route enables the continued development of diazo compounds in chemical biology.


Assuntos
Compostos Azo/síntese química , Paládio/química , Compostos Azo/química , Catálise , Ésteres , Estrutura Molecular , Estereoisomerismo
20.
Chem Commun (Camb) ; 57(39): 4839-4842, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-33870368

RESUMO

A novel universal N-transfer reagent for direct and effective transformation of α-amino ketones, acetamides, and esters to the corresponding α-diazo products under mild basic conditions has been developed. This one-step synthetic approach not only allows for generation of α-substituted-α-diazo carbonyl compounds from α-amino acid derivatives but also permits preparation of α-diazo dipeptides from N-terminal dipeptides (32 examples, up to 91%).


Assuntos
Aminoácidos/química , Compostos Azo/síntese química , Compostos de Diazônio/química , Indicadores e Reagentes/química , Compostos Azo/química , Dipeptídeos/síntese química , Dipeptídeos/química , Estrutura Molecular , Sais/química
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