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1.
Chem Biol Interact ; 330: 109236, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32866467

RESUMO

A series of novel pyrrolopyrimidine urea derivatives were synthesized and evaluated for their anticancer activity against colon cancer cell lines. Compounds showed the remarkable cytotoxic activity on HCT-116 wt cell line. The most potent compound 4c (IC50 = 0.14 µM) induced apoptosis in HCT-116 wt and HCT-116 p53-/- cell lines. Otherwise, treatment of HCT-116 BAX-/-BAK-/- cells with compound 4c didn't lead to activation of apoptosis, suggesting that compound 4c induces apoptotic cell death by activating BAX/BAK-dependent pathway. Moreover, while the compound 4c increase the activation of caspase-3 and caspase-9 levels in HCT-116 wt and HCT-116 p53-/- cells, caspase-3 or caspase-9 activation was not observed in HCT-116 BAX-/-BAK-/- cells. In addition, compound 4c induced mitochondrial apoptosis in cells grown as oncospheroids, which better mimic the in vivo milieu of tumors. 4c treatment also activated JNK along with inhibition of prosurvival kinases such as Akt and ERK 1/2 in HCT-116 wt and HCT-116 p53 -/- cells as well as in HCT-116 BAX-/-BAK-/- cells. Notably, our results indicated that compound 4c induced mitochondrial apoptosis through activation p53-independent apoptotic signaling pathways.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Pirimidinas/farmacologia , Pirróis/farmacologia , Proteína Supressora de Tumor p53/fisiologia , Caspase 3/genética , Caspase 9/genética , Linhagem Celular Tumoral , Neoplasias do Colo/patologia , Técnicas de Inativação de Genes , Células HCT116 , Humanos , Mitocôndrias/metabolismo , Pirimidinas/síntese química , Pirimidinas/química , Pirróis/síntese química , Pirróis/química , Proteína Supressora de Tumor p53/genética , Proteína Killer-Antagonista Homóloga a bcl-2/genética , Proteína X Associada a bcl-2/genética
2.
Biophys Chem ; 264: 106425, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32663708

RESUMO

The novel SARS-CoV-2 is the etiological agent causing the Coronavirus disease 2019 (COVID-19), which continues to become an inevitable pandemic outbreak. Over a short span of time, the structures of therapeutic target proteins for SARS-CoV-2 were identified based on the homology modelled structure of similar SARS-CoV transmission of 2003. Since the onset of the disease, the research community has been looking for a potential drug lead. Out of all the known resolved structures related to SARS-CoV, Main protease (Mpro) is considered an attractive anti-viral drug target on the grounds of its role in viral replication and probable non-interactive competency to bind to any viral host protein. To the best of our knowledge, till date only one compound has been identified and tested in-vivo as a potent inhibitor of Mpro protein, addressed as N3 (PubChem Compound CID: 6323191) and is known to bind irreversibly to Mpro suppressing its activity. Using computational approach, we intend to identify a probable natural fungal metabolite to interact and inhibit Mpro. After screening various small molecules for molecular docking and dynamics simulation, we propose Pyranonigrin A, a secondary fungal metabolite to possess potent inhibitory potential against the Main protease (Mpro) expressed in SARS-CoV-2 virus.


Assuntos
Antivirais/química , Betacoronavirus/enzimologia , Inibidores de Proteases/química , Pironas/química , Pirróis/química , Proteínas não Estruturais Virais/antagonistas & inibidores , Betacoronavirus/patogenicidade , Sítios de Ligação , Cristalografia por Raios X , Cisteína Endopeptidases/química , Cisteína Endopeptidases/genética , Cisteína Endopeptidases/metabolismo , Descoberta de Drogas , Expressão Gênica , Ligação de Hidrogênio , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Homologia de Sequência de Aminoácidos , Termodinâmica , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo
3.
Food Chem ; 328: 127091, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-32474237

RESUMO

Methanol is highly toxic for human, so methanol detection is valuable especially in water and ethanol medium without complicated and time consuming procedure. In this work, we present a new fluorescence probe for direct detection of methanol in aqueous and ethanol medium based on the ZnS:Mn2+ quantum dot (QDs) and soluble N-methylpolypyrrole (NMPPy) hybrid. Moreover, the number of spectroscopic techniques were used to study the chemical composition and optical properties of the resultant QDs as well as investigation on the sensing mechanism toward methanol. Also, methanol can be determined by using ZnS:Mn2+ QDs/NMPPy hybrid based switchable fluorescence sensing system, with high sensitivity, high selectivity and a very good detection limit of 1 mM with linearity in the concentration range of 25-230 mM (~0.1-0.9% v/v) in aqueous solution. Finally, the ZnS:Mn2+ QDs/NMPPy hybrid as optical sensor was successfully utilized to determine the amount of methanol in real alcoholic beverage samples.


Assuntos
Etanol/química , Metanol/análise , Polímeros/química , Pirróis/química , Pontos Quânticos/química , Espectrometria de Fluorescência/instrumentação , Sulfetos/química , Água/química , Compostos de Zinco/química , Corantes Fluorescentes/química , Humanos , Limite de Detecção , Magnésio/química , Metanol/química
4.
Int J Nanomedicine ; 15: 2605-2615, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32368043

RESUMO

Objective: This paper introduces a simple one-step and ultra-fast method for synthesis of highly photothermally active polypyrrole-coated gold nanoparticles. The synthesis process is so simple that the reaction is very fast without the need for any additives or complicated steps. Methodology: Polypyrrole-coated gold nanoparticles (AuPpy NPs) were synthesized by reacting chloroauric acid (HAuCl4) with pyrrole (monomer) in aqueous medium at room temperature. These nanoparticles were characterized by UV-visible-NIR spectrometry, transmission electron microscopy (TEM), AC conductivity, zeta sizer and were evaluated for dark cytotoxicity and photocytotoxicity using human hepatocellular carcinoma (HepG2) cell line as a model for cancer cells. Results: The synthesized AuPpy NPs showed a peak characteristic for gold nanoparticles (530-600 nm, molar ratio dependent) and a wide absorption band along the visible-NIR region with intensity about triple or even quadruple that of polypyrrole synthesized by the conventional FeCl3 method at the same concentration and under the same conditions. TEM imaging showed that the synthesized AuPpy NPs were composed of spherical or semi-spherical gold core(s) of about 4-10 nm coated with distinct layer(s) of polypyrrole seen either loosely or in clusters. Mean sizes of the synthesized nanoparticles range between ~25 and 220 nm (molar ratio dependent). Zeta potentials of the AuPpy NPs preparations indicate their good colloidal stability. AC conductivity values of AuPpy NPs highly surpass that of Ppy prepared by the conventional FeCl3 method. AuPpy NPs were non-toxic even at high concentrations (up to 1000 µM pyrrole monomer equivalent) under dark conditions. Unlikely, light activated the photothermal activity of AuPpy NPs in a dose-dependent manner. Conclusion: This method simply and successfully synthesized AuPpy NPs nanoparticles that represent a safe alternative photothermally active multifunctional tool instead of highly toxic and non-biodegradable gold nanorods.


Assuntos
Materiais Revestidos Biocompatíveis/química , Ouro/química , Luz , Nanopartículas Metálicas/química , Polímeros/química , Pirróis/química , Temperatura , Morte Celular , Cloretos/química , Condutividade Elétrica , Compostos de Ouro/química , Células Hep G2 , Humanos , Nanopartículas Metálicas/ultraestrutura , Tamanho da Partícula , Polímeros/síntese química , Pirróis/síntese química , Espectrofotometria Ultravioleta , Eletricidade Estática
5.
PLoS One ; 15(5): e0232851, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32392238

RESUMO

Here we present the synthesis and characterization of two new conducting materials having a high electro-chemo-mechanical activity for possible applications as artificial muscles or soft smart actuators in biomimetic structures. Glucose-gelatin nanofiber scaffolds (CFS) were coated with polypyrrole (PPy) first by chemical polymerization followed by electrochemical polymerization doped with dodecylbenzensulfonate (DBS-) forming CFS-PPy/DBS films, or with trifluoromethanesulfonate (CF3SO3-, TF) giving CFS-PPy/TF films. The composition, electronic and ionic conductivity of the materials were determined using different techniques. The electro-chemo-mechanical characterization of the films was carried out by cyclic voltammetry and square wave potential steps in bis(trifluoromethane)sulfonimide lithium solutions of propylene carbonate (LiTFSI-PC). Linear actuation of the CFS-PPy/DBS material exhibited 20% of strain variation with a stress of 0.14 MPa, rather similar to skeletal muscles. After 1000 cycles, the creeping effect was as low as 0,2% having a good long-term stability showing a strain variation per cycle of -1.8% (after 1000 cycles). Those material properties are excellent for future technological applications as artificial muscles, batteries, smart membranes, and so on.


Assuntos
Órgãos Artificiais , Materiais Biomiméticos , Materiais Revestidos Biocompatíveis/química , Nanofibras , Polímeros/química , Pirróis/química , Tecidos Suporte , Benzenossulfonatos/química , Condutividade Elétrica , Eletroquímica , Gelatina/química , Glucose/química , Mesilatos/química , Microscopia Eletrônica de Varredura , Músculos , Nanofibras/química , Nanofibras/ultraestrutura , Polimerização , Potenciometria , Espectrometria por Raios X , Espectroscopia de Infravermelho com Transformada de Fourier , Estresse Mecânico , Propriedades de Superfície , Tecidos Suporte/química
6.
Ecotoxicol Environ Saf ; 197: 110644, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32325330

RESUMO

Fludioxonil has been proven valuable as a broad-spectrum fungicide. However, there are concerns about its risk posed to non-target organisms in aquatic environments. In this paper, the mechanism, photoproducts transformation and eco-toxicity of fludioxonil during •OH/1O2-initiated process were systematically studied using quantum chemistry and computational toxicology. The results indicate that the two favorable pathways of •OH/1O2-initiated reactions are both occurred in pyrrole ring. It can conclude that the rate constants of •OH and 1O2 are 1.23 × 1010 and 3.69 × 107 M-1 s-1 at 298K, respectively, which results in half-lives of <2 days in surface waters under sunlit near-surface conditions. Based on toxicity assessments, these photoproducts showed a decreased aquatic toxicity but the majority products are still toxic. This study gives more insight into the chemical transformation mechanism of fludioxonil in aquatic environments.


Assuntos
Dioxóis/análise , Radical Hidroxila/química , Fotólise , Pirróis/análise , Oxigênio Singlete/química , Poluentes Químicos da Água/análise , Reação de Cicloadição , Dioxóis/química , Dioxóis/efeitos da radiação , Ecotoxicologia , Cinética , Pirróis/química , Pirróis/efeitos da radiação , Poluentes Químicos da Água/química , Poluentes Químicos da Água/efeitos da radiação
7.
PLoS One ; 15(4): e0231877, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32315352

RESUMO

Alterations in fibroblast growth factor receptor (FGFR) genes have been identified as potential driver oncogenes. Pharmacological targeting of FGFRs may therefore provide therapeutic benefit to selected cancer patients, and proof-of-concept has been established in early clinical trials of FGFR inhibitors. Here, we present the molecular structure and preclinical characterization of INCB054828 (pemigatinib), a novel, selective inhibitor of FGFR 1, 2, and 3, currently in phase 2 clinical trials. INCB054828 pharmacokinetics and pharmacodynamics were investigated using cell lines and tumor models, and the antitumor effect of oral INCB054828 was investigated using xenograft tumor models with genetic alterations in FGFR1, 2, or 3. Enzymatic assays with recombinant human FGFR kinases showed potent inhibition of FGFR1, 2, and 3 by INCB054828 (half maximal inhibitory concentration [IC50] 0.4, 0.5, and 1.0 nM, respectively) with weaker activity against FGFR4 (IC50 30 nM). INCB054828 selectively inhibited growth of tumor cell lines with activation of FGFR signaling compared with cell lines lacking FGFR aberrations. The preclinical pharmacokinetic profile suggests target inhibition is achievable by INCB054828 in vivo with low oral doses. INCB054828 suppressed the growth of xenografted tumor models with FGFR1, 2, or 3 alterations as monotherapy, and the combination of INCB054828 with cisplatin provided significant benefit over either single agent, with an acceptable tolerability. The preclinical data presented for INCB054828, together with preliminary clinical observations, support continued investigation in patients with FGFR alterations, such as fusions and activating mutations.


Assuntos
Morfolinas/uso terapêutico , Neoplasias/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Administração Oral , Animais , Linhagem Celular Tumoral , Feminino , Meia-Vida , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Camundongos SCID , Morfolinas/química , Morfolinas/farmacocinética , Neoplasias/patologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacocinética , Pirimidinas/química , Pirimidinas/farmacocinética , Pirróis/química , Pirróis/farmacocinética , Ratos , Ratos Nus , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Alkaloids Chem Biol ; 83: 1-112, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32098648

RESUMO

Lamellarins are marine alkaloids containing fused 14-phenyl-6H-[1]benzopyrano[4',3':4,5]pyrrolo[2,1-a]isoquinoline or non-fused 3,4-diarylpyrrole-2-carboxylate ring systems. To date, more than 50 lamellarins have been isolated from a variety of marine organisms, such as mollusks, tunicates, and sponges. Many of them, especially fused type I lamellarins, exhibit impressive biological activity, such as potent cytotoxicity, topoisomerase I inhibition, protein kinases inhibition, and anti-HIV-1 activity. Due to their useful biological activity and limited availability from natural sources, a number of synthetic methods have been developed. In this chapter, we present an updated and comprehensive review on lamellarin alkaloids summarizing their isolation, synthesis, and biological activity.


Assuntos
Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Fármacos Anti-HIV/farmacologia , Antineoplásicos/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Pirróis/isolamento & purificação , Pirróis/farmacologia , Inibidores da Topoisomerase I/farmacologia , Alcaloides/síntese química , Alcaloides/química , Animais , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/química , Fármacos Anti-HIV/isolamento & purificação , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Humanos , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/isolamento & purificação , Pirróis/síntese química , Pirróis/química , Inibidores da Topoisomerase I/síntese química , Inibidores da Topoisomerase I/química , Inibidores da Topoisomerase I/isolamento & purificação
9.
Chemistry ; 26(14): 3173-3180, 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32083355

RESUMO

Development of novel bioimaging materials that exhibit organelle specific accumulation continues to be at the forefront of research interests and efforts. Among the various subcellular organelles, mitochondria, which are found in the cytoplasm of eukaryotic cells, are of particular interest in relation to their vital function. To date, most molecular probes that target mitochondria utilise delocalised lipophilic cations such as triphenylphosphonium and pyridinium. However, the use of such charged motifs is known to be detrimental to the working function of the mitochondrial transmembrane potential and there remains a strong case for development of neutral mitochondrial fluorescent probes. Herein, we demonstrate for the first time the exploitation of diketopyrrolopyrrole-based chemistries for the realisation of a neutral fluorescent probe that exhibits organelle specific accumulation within the mitochondria at the nanomolar level. The synthesised probe, which bears a neutral triphenylphosphine oxide moiety, exhibits a large Stokes shift and high fluorescence quantum yield in water, both highly sought-after properties in the development of bioimaging agents. In vitro studies reveal no interference with cell metabolism when tested for the human MCF7 breast cancer cell and nanomolar subcellular organelle colocalisation with commercially available mitochondrial staining agent Mitotracker Red. In light of its novelty, neutral structure and the preferential accumulation at nanomolar concentrations we anticipate this work to be of significant interest for the increasingly larger community devoted to the realisation of neutral mitochondrial selective systems and more widely to those engaged in the rational development of superior organic architectures in the biological field.


Assuntos
Corantes Fluorescentes/química , Cetonas/química , Mitocôndrias/metabolismo , Compostos Organofosforados/química , Pirróis/química , Técnicas Biossensoriais , Humanos , Luz , Células MCF-7 , Potencial da Membrana Mitocondrial/fisiologia , Estrutura Molecular , Imagem Óptica , Compostos Orgânicos/química , Relação Estrutura-Atividade
10.
Nat Commun ; 11(1): 1015, 2020 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-32081914

RESUMO

Many reagents have been developed for cysteine-specific protein modification. However, few of them allow for multi-functionalization of a single Cys residue and disulfide bridging bioconjugation. Herein, we report 3-bromo-5-methylene pyrrolones (3Br-5MPs) as a simple, robust, and versatile class of reagents for cysteine-specific protein modification. These compounds can be facilely synthesized via a one-pot mild reaction and they show comparable tagging efficiency but higher cysteine specificity than the maleimide counterparts. The addition of cysteine to 3Br-5MPs generates conjugates that are amenable to secondary addition by another thiol or cysteine, making 3Br-5MPs valuable for multi-functionalization of a single cysteine and disulfide bridging bioconjugation. The labeling reaction and subsequent treatments are mild enough to produce stable and active protein conjugates for biological applications.


Assuntos
Cisteína/química , Proteínas/química , Técnicas de Química Sintética/métodos , Dissulfetos/química , Indicadores e Reagentes/química , Fenômenos de Química Orgânica , Pirróis/química , Somatostatina/química
11.
Food Chem ; 317: 126458, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32109656

RESUMO

A kinetic model for Maillard reaction (MR) model system of d-glucose and l-lysine was established; activation energy (Ea) of each step was calculated. Potential generation pathways of furosine and pyrraline were a combination of either 3-deoxyglucosone (3-DG) or methylglyoxal (MG) with l-lysine. Ea value for furosine generated through 3-DG pathway was 81.70 ± 14.01 kJ mol-1, which was significantly higher than that through MG pathway (52.08 ± 4.48 kJ mol-1). As for pyrraline, Ea for the 3-DG pathway (53.45 ± 4.02 kJ mol-1) was significantly lower than that through the MG pathway (110.22 ± 18.77 kJ mol-1). Results of the kinetic study indicated that furosine was preferred to be generated through the MG pathway since MG is more likely to react with each other and form a furan ring as a precursor of furosine. Pyrraline was more easily to be generated from the 3-DG pathway through cyclization of 1,4-dicarbonyl compounds to pyrrole.


Assuntos
Glucose/química , Lisina/análogos & derivados , Lisina/química , Reação de Maillard , Norleucina/análogos & derivados , Pirróis/química , Desoxiglucose/análogos & derivados , Desoxiglucose/química , Cinética , Norleucina/química , Aldeído Pirúvico/química
12.
Chemosphere ; 248: 126102, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32045978

RESUMO

A novel adsorbent, the uniform fiber ball (UFB) loaded with polypyrrole (UFB-PPy), was synthesized for Cr(VI) removal from water in this paper. The structure of the UFB and UFB-PPy were characterized by SEM, EDS, FT-IR, BET, XPS and TG. The adsorption properties of UFB-PPy towards Cr(VI) were investigated by the effects of temperature, initial concentration of Cr(VI), interfering ions and contact time in batch experiments, the isothermal models (Langmuir, Freundlich and Temkin) and the kinetic models (Pseudo first-order kinetic, Pseudo second-order kinetic and Intra-particle diffusion models) were used to describe the adsorption behavior. The effects of the initial concentration and flow rate of the Cr(VI) solution in the column experiments were also studied, and the dynamic models (Yoon-Nelson, Adams-Bohart and Wolborska model) were applied to predict the adsorption performance. The Cr(VI) removal mechanism of UFB-PPy was revealed by studying the effect of pH on adsorption, testing of Cl-, and analyzing the XPS. The results showed that UFB-PPy exhibited excellent adsorption properties for Cr(VI) both in batch and column adsorption. The possible adsorption mechanism involved electrostatic attraction, ion exchange and reduction. Conveniently, the chromium resources can be recovered with the form of high-purity Cr2O3 by simple calcination of Cr(VI)-captured UFB-PPy (UFB-PPy-Cr).


Assuntos
Cromo/análise , Modelos Teóricos , Polímeros/química , Pirróis/química , Poluentes Químicos da Água/análise , Purificação da Água/métodos , Adsorção , Difusão , Concentração de Íons de Hidrogênio , Troca Iônica , Cinética , Papel
14.
Chemistry ; 26(28): 6205-6213, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31971638

RESUMO

The degradation of chlorophyll, the omnipresent green pigment, has been investigated intensively over the last 30 years resulting in many elucidated tetrapyrrolic degradation products. With a comparison to the degradation of the structurally similar heme, we hereby propose a novel additional chlorophyll degradation mechanism to mono- and dipyrrolic products. This is the first proof of the occurrence of a family of mono- and dipyrrols in leaves that are previously only known as heme degradation products. This product family is also found in spit and feces of herbivores with specific metabolomic patterns reflecting the origin of the samples. Based on chromatographic and mass spectrometric evidence as well as on mechanistic considerations we also suggest several tentative new degradation products. One of them, dihydro BOX A, was fully confirmed as a novel natural product by synthesis and comparison of its spectroscopic data.


Assuntos
Clorofila/metabolismo , Pirróis/metabolismo , Herbivoria , Folhas de Planta/química , Plantas/química , Plantas/metabolismo , Pirróis/química
15.
Eur J Med Chem ; 188: 111988, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31901746

RESUMO

In connection with our continued research to generate new aza-fused heteroaromatic chemical scaffolds, we developed a highly atom-economical three-component route to novel 3,4-dihydropyrrolo[1,2-a]pyrazine ring skeleton multi-functionalized on the pyrazine unit. This [4+1+1] annulation approach led us to gain access to a new N-fused bicyclic chemical space having two distinctive functional groups (heteroaryl and aroyl) in a trans manner. Investigation of anticancer activity of the synthesized compounds and their derivatives revealed that (3R*,4S*)-3-(4-bromophenyl)-4-(4-fluorobenzoyl)-2-(2-oxo-2-phenylethyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-2-ium bromide (3h) has potent anticancer activity. 3h significantly inhibited cell viability in prostate cancer cells (PC-3) and breast cancer cells (MCF-7) with IC50 value of 1.18 ± 0.05 µM and 1.95 ± 0.04 µM, respectively. In addition, 3h strongly reduced cell migration in a dose dependent manner, and induced apoptosis via caspase-3 activation and cleavage of PARP in PC-3 and MCF-7 cells. Our results in this study imply that 3h can be a potential anticancer agent against prostate cancer and breast cancer.


Assuntos
Antineoplásicos/farmacologia , Pirazinas/farmacologia , Pirróis/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Poli(ADP-Ribose) Polimerases/metabolismo , Pirazinas/síntese química , Pirazinas/química , Pirróis/síntese química , Pirróis/química
16.
Molecules ; 25(2)2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31936802

RESUMO

This manuscript reports the improved synthesis of the α,α,α,α isomer of tetra-p-iodophenyl tetra-methyl calix[4]pyrrole and the X-ray characterization of two solvate polymorphs. In the solid state, the calix[4]pyrrole receptor adopts the cone conformation, including one acetonitrile molecule in its aromatic cavity by establishing four convergent hydrogen bonds between its nitrogen atom and the four pyrrole NHs of the former. The inclusion complexes pack into rods, displaying a unidirectional orientation. In turn, the rods form flat 2D-layers by alternating the orientation of their p-iodo substituents. The 2D layers stack on top of another, resulting in a head-to-head and tail-to-tail orientation of the complexes or their exclusive arrangement in a head-to-tail geometry. The dissimilar stacking of the layers yields two solvate polymorphs that are simultaneously present in the structures of the single crystals. The ratio of the two polymorph phases is regulated by the amount of acetonitrile added to the chloroform solutions from which the crystals grow. Halogen bonding interactions are highly relevant in the crystal lattices of the two polymorphs. We analyzed and characterized these interactions by means of density functional theory (DFT) calculations and several computational tools. Remarkably, single crystals of a solvate containing two acetonitrile molecules per calix[4]pyrrole were obtained from pure acetonitrile solution.


Assuntos
Modelos Moleculares , Pirróis/química , Pirróis/síntese química , Cristalografia por Raios X , Isomerismo , Estrutura Molecular
17.
Carbohydr Polym ; 232: 115801, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31952600

RESUMO

The aim of this study was to use of bacterial cellulose/polypyrrole/TiO2-Ag (BC/PPy/TiO2-Ag) nanocomposite film to detect and measure the growth of 5 pathogenic bacteria. For this purpose, at first, 13 BC/PPy/TiO2-Ag films were fabricated, then bacterial suspensions were prepared according to McFarland standard. The results showed that by increasing the bacterial concentration, the electrical resistance of sensors was decreased and there was a relation between bacterial concentration and bacterial type with electrical resistance change of sensors. The obtained data showed that the sensitivity of the sensors was increased with increasing the concentration of polypyrrole and TiO2-Ag. FT-IR and SEM tests were performed to investigate the interaction between nanoparticles and determine the size of nanoparticles. The BC/PPy/TiO2-Ag biosensors are portable and the response time of these sensors is very short for target analysis. Therefore, these sensors have the potential to improve biological safety as diagnostic tools.


Assuntos
Aeromonas hydrophila/química , Celulose/química , Nanocompostos/química , Staphylococcus aureus/química , Staphylococcus epidermidis/química , Aeromonas hydrophila/crescimento & desenvolvimento , Tamanho da Partícula , Polímeros/química , Pirróis/química , Prata/química , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus epidermidis/crescimento & desenvolvimento , Propriedades de Superfície , Titânio/química
18.
Talanta ; 209: 120507, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31892003

RESUMO

To overcome the poor conductivities and promote the application in the biosensors of metal-organic frameworks (MOFs), a simple approach was employed to improve their overall conductivity by adjusting the metal centers of MOFs and coating conductive polypyrrole (PPy) in the work. An unprecedented molybdenum oxide-based three-dimensional MOFs with helical channels (CuTRZMoO4) was synthesized based on MoO4-, Cu2+ ions and 1,2,3-trz for the first time, then combined with PPy to fabricate hybrid composites (CuTRZMoO4@PPy-n) with both advantages. The CuTRZMoO4 modified glassy carbon electrode show high sensitivity for detecting the neurotransmitter dopamine (DA), and the CuTRZMoO4@PPy-2 modified glassy carbon electrode has the highest catalytical activity to DA with the linear detection range from 1 µM to 100 µM and the detection limit of 80 nM (S/N = 3) by differential pulse voltammetry (DPV). Moreover, the developed biosensor has good selectivity, reproducibility and stability. The concept behinds the new architecture to modify electrodes should promote the further development of MOF-based biosensors.


Assuntos
Dopamina/sangue , Estruturas Metalorgânicas/química , Molibdênio/química , Nanocompostos/química , Óxidos/química , Polímeros/química , Pirróis/química , Técnicas Biossensoriais/métodos , Carbono/química , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Eletrodos , Humanos , Limite de Detecção , Estruturas Metalorgânicas/síntese química
19.
Molecules ; 25(2)2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31936442

RESUMO

A novel generation of indole-2,3-quinodimethanes via the deamination of 1,2,3,4-tetrahydropyrrolo[s3,4-b]indoles is reported.


Assuntos
Indóis/química , Pirróis/química , Desaminação , Indóis/síntese química , Nitritos/química , Pirróis/síntese química
20.
Chemphyschem ; 21(3): 257-262, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-31793133

RESUMO

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


Assuntos
Carbazóis/química , Glucosídeos/química , Compostos Macrocíclicos/química , Pirróis/química , Receptores Artificiais/química , Ligação de Hidrogênio , Ligantes , Conformação Molecular , Termodinâmica
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