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1.
J Mol Graph Model ; 104: 107851, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33556646

RESUMO

The SARS-CoV-2 virus is causing COVID-19, an ongoing pandemic, with extraordinary global health, social, and political implications. Currently, extensive research and development efforts are aimed at producing a safe and effective vaccine. In the interim, small molecules are being widely investigated for antiviral effects. With respect to viral replication, the papain-like (PLpro) and main proteases (Mpro), are critical for processing viral replicase polypeptides. Further, the PLpro possesses deubiquitinating activity affecting key signalling pathways, including inhibition of interferon and innate immune antagonism. Therefore, inhibition of PLpro activity with small molecules is an important research direction. Our aim was to focus on identification of potential inhibitors of the protease activity of SARS-CoV-2 PLpro. We investigated 300 small compounds derived predominantly from our OliveNet™ library (222 phenolics) and supplemented with synthetic and dietary compounds with reported antiviral activities. An initial docking screen, using the potent and selective noncovalent PLpro inhibitor, GRL-0617 as a control, enabled a selection of 30 compounds for further analyses. From further in silico analyses, including docking to scenes derived from a publicly available molecular dynamics simulation trajectory (100 µs PDB 6WX4; DESRES-ANTON-11441075), we identified lead compounds for further in vitro evaluation using an enzymatic inhibition assay measuring SARS-CoV-2 PLpro protease activity. Our findings indicate that hypericin possessed inhibition activity, and both rutin and cyanidin-3-O-glucoside resulted in a concentration-dependent inhibition of the PLpro, with activity in the micromolar range. Overall, hypericin, rutin, and cyanidin-3-O-glucoside can be considered lead compounds requiring further characterisation for potential antiviral effects in appropriate model systems.


Assuntos
Antocianinas/química , Antivirais/química , Perileno/análogos & derivados , Rutina/química , Bibliotecas de Moléculas Pequenas/química , Antocianinas/farmacologia , Antivirais/farmacologia , Sítios de Ligação , /virologia , /metabolismo , Ensaios Enzimáticos , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Perileno/química , Perileno/farmacologia , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Teoria Quântica , Rutina/farmacologia , /efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/farmacologia , Termodinâmica
2.
J Nat Prod ; 84(2): 436-443, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33560122

RESUMO

A new axial chiral binaphtoquinone, hypocrellone (1), and a new perylenequinone, hypomycin F (2), were isolated from the stromata of Hypocrella bambusae, together with five known compounds, 3-7. The structures of 1 and 2 were assigned by spectroscopic and HRESIMS data analyses. The axial chirality of 1 was determined by electronic circular dichroism data analysis, and the absolute configurations of 2 and 3 were determined by X-ray crystallography. The axial chirality of 7 was determined by UV-induced photooxidation from 4. Compounds 1, 4, and 5 showed inhibitory activity against pseudotyped SARS-CoV-2 infection in 293T-ACE2 cells with IC50 values of 0.17, 0.038, and 0.12 µM. Compounds 4 and 5 were also active against live SARS-CoV-2 infection with EC50 values of 0.22 and 0.21 µM, respectively. Further cell-cell fusion assays, surface plasmon resonance assays, and molecular docking studies revealed that 4 and 5 could bind with the receptor-binding domain of SARS-CoV-2 S protein to prevent its interaction with human angiotensin-converting enzyme II receptor. Our results revealed that 4 and 5 are potential SARS-CoV-2 entry inhibitors.


Assuntos
Hypocreales/química , Naftoquinonas/farmacologia , Perileno/análogos & derivados , Quinonas/farmacologia , Internalização do Vírus/efeitos dos fármacos , Naftoquinonas/química , Perileno/química , Perileno/farmacologia , Quinonas/química , /fisiologia
3.
Ecotoxicol Environ Saf ; 209: 111841, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33387772

RESUMO

We report a new green route for preparing MnO2/perlite nanocomposites (NCs) by leaf extract of Hypericum perforatum. Characterization of the physicochemical properties of the MnO2/perlite-NCs was performed using XRD, FESEM, EDX, FT-IR, and DLS techniques. Furthermore, their effects on the phytochemical classification and growth parameters of H. perforatum shoot cultures were assessed. According to the FESEM image, the synthesized spherical MnO2 nanoparticles on the sheet-like structure of nano-perlite were formed, ranging about 20-50 nm. In addition, based on the EDX spectra, the elemental analysis showed the presence of Carbon, Oxygen, Silicon, Aluminum, and Manganese elements in the as-synthesized MnO2/perlite-NCs. Biological studies confirmed that nano-perlite and MnO2/perlite-NCs were non-toxic to H. perforatum shoot cultures and showed positive effects on plant growth in specific concentrations. Overall, phytochemical classification demonstrated that the terpenoids decreased in the evaluated treatments, while hypericin and pseudohypericin were increased in some treatments (25, 50 and 150 mg/L of nano-perlite) relative to control. Metabolomics results suggested that both nano-perlite and MnO2/perlite-NCs can be used as elicitors and new nanofertilizers for generating some secondary metabolites.


Assuntos
Hypericum/fisiologia , Manganês/metabolismo , Nanocompostos , Óxido de Alumínio , Hypericum/crescimento & desenvolvimento , Compostos de Manganês , Nanopartículas , Óxidos/farmacologia , Perileno/análogos & derivados , Compostos Fitoquímicos/farmacologia , Óleos Vegetais , Dióxido de Silício , Espectroscopia de Infravermelho com Transformada de Fourier
4.
Life Sci ; 266: 118874, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33358904

RESUMO

AIMS: Hypericin (HYP) from Hypericum perforatum has cytotoxic effects on a variety of malignant cell types, but the pattern of gene expression mediating the effect is largely unknown. Here we sought to analyze the response of U87 glioblastoma (GBM) cell lines in response to HYP. MATERIALS AND METHODS: U87 cell line was treated by HYP. Cytotoxicity was assessed using MTT and Annexin V/PI assays. Gene expression profile was obtained using high-throughput sequencing. Enrichment analysis was performed on differentially expressed genes (DEGs). Upstream transcription factors and microRNAs regulating DEGs were predicted. The effects of DEGs on survival of GBM patients were calculated. Protein-protein interaction analysis was conducted to obtain key altered genes. The possible effect of HYP treatment on immunity response was evaluated. KEY FINDINGS: The IC50 of HYP on U87 cell line was determined to be 1.5 µg/ml. The main type of cell death was apoptosis. A total of 312 DEGs were found. Affected Gene Ontology terms and pathways were identified. Analysis of upstream modulators of DEGs pointed out to transcription factors that significantly overlap with GBM stem cell transcription factor. Survival analysis suggested that HYP works best for the mesenchymal subtype patients. Tumor infiltration analysis predicted that HYP may affect Treg and macrophage infiltration in vivo. Using expression pattern of GBM patients and HYP-induced DEGs we suggested Fedratinib as a complementary drug to HYP. SIGNIFICANCE: Our study represents the response of U87 cell line to HYP, with analyses on survival, transcription factors and personalization according to GBM subtype.


Assuntos
Antineoplásicos/farmacologia , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioblastoma/tratamento farmacológico , Perileno/análogos & derivados , Transcriptoma/efeitos dos fármacos , Apoptose , Proliferação de Células , Glioblastoma/genética , Glioblastoma/patologia , Humanos , Perileno/farmacologia , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas
5.
J Vis Exp ; (161)2020 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-32744529

RESUMO

The interest on nitrogen-containing heterocycles has expanded rapidly in the synthetic community since they are important motifs for new drugs. Traditionally, they were synthesized through thermal cycloaddition reactions, whereas today, photocatalysis is preferred due to the mild and efficient conditions. With this focus, a new photocatalytic method for the synthesis of nitrogen-containing heterocycles is highly desired. Here, we report a protocol for the biosynthesis of cercosporin, which could function as a metal-free photocatalyst. We then illustrate cercosporin-photocatalyzed protocols for the synthesis of nitrogen-containing heterocycles 1,2,3-thiadiazoles through annulation of azoalkenes with KSCN, and synthesis of 1,4,5,6-tetrahydropyridazines [4+2] through cyclodimerization of azoalkenes under mild conditions, respectively. As a result, there is a new bridge between the microbial fermentation method and organic synthesis in a mild, cost-effective, environmentally friendly and sustainable manner.


Assuntos
Alcenos/química , Compostos Azo/química , Perileno/análogos & derivados , Técnicas de Química Sintética , Reação de Cicloadição , Metais/química , Nitrogênio/química , Perileno/química
6.
Virus Res ; 286: 198068, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32565126

RESUMO

The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a renewed interest in studying the role of the spike S glycoprotein in regulating coronavirus infections in the natural host. Taking advantage of the cryo-electron microscopy structure of SARS-CoV-2 S trimer in the prefusion conformation, we performed a virtual screening simulation with the aim to identify novel molecules that could be used as fusion inhibitors. The spike glycoprotein structure has been completed using modeling techniques and its inner cavity, needful for the postfusion transition of the trimer, has been scanned for the identification of strongly interacting available drugs. Finally, the stability of the protein-drug top complexes has been tested using classical molecular dynamics simulations. The free energy of interaction of the molecules to the spike protein has been evaluated through the MM/GBSA method and per-residue decomposition analysis. Results have been critically discussed considering previous scientific knowledge concerning the selected compounds and sequence alignments have been carried out to evaluate the spike glycoprotein similarity among the betacoronavirus family members. Finally, a cocktail of drugs that may be used as SARS-CoV-2 fusion inhibitors has been suggested.


Assuntos
Antivirais/química , Betacoronavirus/química , Compostos Heterocíclicos de 4 ou mais Anéis/química , Indóis/química , Perileno/análogos & derivados , Glicoproteína da Espícula de Coronavírus/química , Sulfonamidas/química , Antivirais/farmacologia , Betacoronavirus/patogenicidade , Sítios de Ligação , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Expressão Gênica , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Ensaios de Triagem em Larga Escala , Humanos , Indóis/farmacologia , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Pandemias , Perileno/química , Perileno/farmacologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Multimerização Proteica , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Glicoproteína da Espícula de Coronavírus/antagonistas & inibidores , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Sulfonamidas/farmacologia , Termodinâmica , Interface Usuário-Computador , Internalização do Vírus/efeitos dos fármacos
7.
Life Sci ; 255: 117858, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32497635

RESUMO

At present, cervical cancer is the fourth leading cause of cancer among women worldwide with no effective treatment options. In this study we aimed to evaluate the efficacy of hypericin (HYP) encapsulated on Pluronic® P123 (HYP/P123) photodynamic therapy (PDT) in a comprehensive panel of human cervical cancer-derived cell lines, including HeLa (HPV 18-positive), SiHa (HPV 16-positive), CaSki (HPV 16 and 18-positive), and C33A (HPV-negative), compared to a nontumorigenic human epithelial cell line (HaCaT). Were investigated: (i) cell cytotoxicity and phototoxicity, cellular uptake and subcellular distribution; (ii) cell death pathway and cellular oxidative stress; (iii) migration and invasion. Our results showed that HYP/P123 micelles had effective and selective time- and dose-dependent phototoxic effects on cervical cancer cells but not in HaCaT. Moreover, HYP/P123 micelles accumulated in endoplasmic reticulum, mitochondria and lysosomes, resulting in photodynamic cell death mainly by necrosis. HYP/P123 induced cellular oxidative stress mainly via type II mechanism of PDT and inhibited cancer cell migration and invasion mainly via MMP-2 inhibition. Taken together, our results indicate a potentially useful role of HYP/P123 micelles as a platform for HYP delivery to more specifically and effectively treat cervical cancers through PDT, suggesting they are worthy for in vivo preclinical evaluations.


Assuntos
Antineoplásicos/administração & dosagem , Nanopartículas , Perileno/análogos & derivados , Fotoquimioterapia/métodos , Neoplasias do Colo do Útero/tratamento farmacológico , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Sistemas de Liberação de Medicamentos , Feminino , Células HeLa , Humanos , Micelas , Invasividade Neoplásica , Estresse Oxidativo/efeitos dos fármacos , Perileno/administração & dosagem , Perileno/farmacologia , Poloxaleno/química , Fatores de Tempo , Neoplasias do Colo do Útero/patologia
8.
Chem Commun (Camb) ; 56(40): 5358-5361, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32347872

RESUMO

A triplex-forming oligonucleotide (TFO) linear probe containing perylene derivatives was synthesized. The TFO linear probe formed a remarkably stable triplex with a target DNA duplex, resulting in the light-up of fluorescence emission. The sensitivity was extremely high even at pH 7. Detection of PCR-amplified target DNA was demonstrated.


Assuntos
DNA/análise , Oligonucleotídeos/química , Perileno/análogos & derivados , DNA/química , DNA/genética , Corantes Fluorescentes/química , Humanos , Hibridização de Ácido Nucleico , Oligonucleotídeos/genética , Compostos Orgânicos/química , Reação em Cadeia da Polimerase , Receptores Androgênicos/genética , Espectrometria de Fluorescência/métodos
9.
Chemosphere ; 253: 126751, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32302913

RESUMO

A novel n-n type inorganic/organic heterojunction of flaky-like BiOCl/PDI photocatalyst was constructed by water bath heating method. Meanwhile, a simple method - secondary self-assembly was used to prepare the BiOCl/PDI with a special band structure. The photocatalytic activities were evaluated by degrading aqueous organic pollutants under visible light (λ > 420 nm). The removal rates of 5 mg L-1 phenol (non-ionic type), methyl orange (MO, anionic type), rhodamine B (RhB, cationic type) and 10 mg L-1 RhB by secondary self-assembly BiOCl/PDI (BiOCl/PDI-2) were 8.0%, 3.4%, 27.8% and 78.9% higher than self-assembly BiOCl/PDI (BiOCl/PDI-1) under visible light (λ > 420 nm). The better photocatalytic activity for BiOCl/PDI-2 was attributed to the optimization of energy-band structures, which arose from different exposed surfaces, narrower interplanar spacing and stronger visible light absorption performance. Under acidic condition, BiOCl/PDI-2 showed a good photocatalytic activity, which was not affected by neutral ionic intensity and had good recycling properties. Moreover, the photocatalytic mechanism was explored by free radical capture test and electron paramagnetic resonance (EPR), and contribution of active species was calculated. The main active species of BiOCl/PDI-2 were ·O2-, 1O2 and h+. Our work may provide a route to design efficient inorganic/organic heterojunctions for organic pollutants degradation.


Assuntos
Bismuto/química , Imidas/química , Luz , Nanoestruturas/química , Perileno/análogos & derivados , Poluentes Químicos da Água/análise , Compostos Azo/análise , Compostos Azo/efeitos da radiação , Catálise , Perileno/química , Fenóis/análise , Fenóis/efeitos da radiação , Rodaminas/análise , Rodaminas/efeitos da radiação , Propriedades de Superfície , Poluentes Químicos da Água/efeitos da radiação
10.
J Phys Chem A ; 124(12): 2497-2504, 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32126168

RESUMO

Hypericin is one of the most efficient photosensitizers used in photodynamic tumor therapy (PDT). The reported treatments of this drug reach from antidepressive, antineoplastic, antitumor and antiviral activity. We show that hypericin can be optically detected down to a single molecule at ambient conditions. Hypericin can even be observed inside of a cancer cell, which implies that this drug can be directly used for advanced microscopy techniques (PALM, spt-PALM, or FLIM). Its photostability is large enough to obtain single molecule fluorescence, surface enhanced Raman spectra (SERS), fluorescence lifetime, antibunching, and blinking dynamics. Sudden spectral changes can be associated with a reorientation of the molecule on the particle surface. These properties of hypericin are very sensitive to the local environment. Comparison of DFT calculations with SERS spectra show that both the neutral and deprotonated form of hypericin can be observed on the single molecule and ensemble level.


Assuntos
Perileno/análogos & derivados , Fármacos Fotossensibilizantes/química , Linhagem Celular Tumoral , Teoria da Densidade Funcional , Fluorescência , Humanos , Microscopia de Fluorescência , Modelos Químicos , Perileno/química , Imagem Individual de Molécula , Análise Espectral Raman
11.
PLoS One ; 15(3): e0230362, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32176712

RESUMO

Fungi in the genus Cercospora cause crop losses world-wide on many crop species. The wide host range and success of these pathogens has been attributed to the production of a photoactivated toxin, cercosporin. We engineered tobacco for resistance to Cercospora nicotianae utilizing two strategies: 1) transformation with cercosporin autoresistance genes isolated from the fungus, and 2) transformation with constructs to silence the production of cercosporin during disease development. Three C. nicotianae cercosporin autoresistance genes were tested: ATR1 and CFP, encoding an ABC and an MFS transporter, respectively, and 71cR, which encodes a hypothetical protein. Resistance to the pathogen was identified in transgenic lines expressing ATR1 and 71cR, but not in lines transformed with CFP. Silencing of the CTB1 polyketide synthase and to a lesser extent the CTB8 pathway regulator in the cercosporin biosynthetic pathway also led to the recovery of resistant lines. All lines tested expressed the transgenes, and a direct correlation between the level of transgene expression and disease resistance was not identified in any line. Resistance was also not correlated with the degree of silencing in the CTB1 and CTB8 silenced lines. We conclude that expression of fungal cercosporin autoresistance genes as well as silencing of the cercosporin pathway are both effective strategies for engineering resistance to Cercospora diseases where cercosporin plays a critical role.


Assuntos
Ascomicetos/genética , Resistência à Doença/genética , Farmacorresistência Fúngica/genética , Inativação Gênica , Genes Fúngicos , Engenharia Genética , Perileno/análogos & derivados , Tabaco/microbiologia , Ascomicetos/efeitos dos fármacos , Resistência à Doença/efeitos dos fármacos , Farmacorresistência Fúngica/efeitos dos fármacos , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Inativação Gênica/efeitos dos fármacos , Perileno/farmacologia , Plantas Geneticamente Modificadas , Transformação Genética , Transgenes
12.
Molecules ; 25(6)2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32204413

RESUMO

Perylenediimide (PDI) is one of the most important classes of dyes and is intensively explored in the field of functional organic materials. The functionalization of this electron-deficient aromatic core is well-known to tune the outstanding optoelectronic properties of PDI derivatives. In this respect, the functionalization has been mostly addressed in bay-positions to halogenated derivatives through nucleophilic substitutions or metal-catalyzed coupling reactions. Being aware of the synthetic difficulties of obtaining the key intermediate 1-bromoPDI, we will present as an alternative in this review the potential of 1-nitroPDI: a powerful building block to access a large variety of PDI-based materials.


Assuntos
Imidas/química , Nitrocompostos/síntese química , Perileno/análogos & derivados , Catálise , Estrutura Molecular , Nitrocompostos/química , Perileno/química
13.
Int J Mol Sci ; 21(3)2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32019072

RESUMO

Shiraia mycelial culture is a promising biotechnological alternative for the production of hypocrellin A (HA), a new photosensitizer for anticancer photodynamic therapy (PDT). The extractive fermentation of intracellular HA in the nonionic surfactant Triton X-100 (TX100) aqueous solution was studied in the present work. The addition of 25 g/L TX100 at 36 h of the fermentation not only enhanced HA exudation to the broth by 15.6-fold, but stimulated HA content in mycelia by 5.1-fold, leading to the higher production 206.2 mg/L, a 5.4-fold of the control on day 9. After the induced cell membrane permeabilization by TX100 addition, a rapid generation of nitric oxide (NO) and hydrogen peroxide (H2O2) was observed. The increase of NO level was suppressed by the scavenger vitamin C (VC) of reactive oxygen species (ROS), whereas the induced H2O2 production could not be prevented by the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO), suggesting that NO production may occur downstream of ROS in the extractive fermentation. Both NO and H2O2 were proved to be involved in the expressions of HA biosynthetic genes (Mono, PKS and Omef) and HA production. NO was found to be able to up-regulate the expression of transporter genes (MFS and ABC) for HA exudation. Our results indicated the integrated role of NO and ROS in the extractive fermentation and provided a practical biotechnological process for HA production.


Assuntos
Ascomicetos/química , Peróxido de Hidrogênio/metabolismo , Óxido Nítrico/metabolismo , Octoxinol/farmacologia , Perileno/análogos & derivados , Fármacos Fotossensibilizantes/metabolismo , Quinonas/metabolismo , Biotecnologia , Membrana Celular/metabolismo , Fermentação , Micélio/química , Perileno/metabolismo , Fenol , Fotoquimioterapia
14.
Pharm Dev Technol ; 25(4): 482-491, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31903830

RESUMO

Hypericin (Hyp), a natural hydrophobic and photoactive pigment, and methylene blue (MB), a hydrophilic cationic dye, are utilized as photosensitizer (PS) for photodynamic therapy of cancer. Bioadhesive and thermoresponsive polymeric systems can improve the drug availability by increasing the contact time between the system and the mucosa and also controlling the drug release. In this work, an accelerated physicochemical stability study of binary polymeric systems composed of poloxamer 407 (Polox) and Carbopol 934 P (Carb) for MB or Hyp release was performed. Formulations were prepared containing Polox (20%, w/w), Carb (0.15%, w/w) and MB (0.25%, w/w) or Hyp (0.01%, W/W) and submitted to different stress conditions (5 ± 3 °C, 25 ± 2 °C and 40 ± 2 °C with relative humidity of 75 ± 5%) during 180 days. The samples were analyzed as macroscopic characteristics, photosensitizer content and mechanical properties by texture profile analysis. Both systems displayed decrease of photosensitizer content less than 5% during 180 days. MB-system showed an undefined reaction model, while Hyp-system displayed PS decay following a pseudo first-order reaction. Systems also displayed stable mechanical characteristics. The pharmaceutical analyses showed the good physicochemical stability of the bioadhesive platform for delivery Hyp and MB in photodynamic therapy.


Assuntos
Preparações de Ação Retardada/química , Azul de Metileno/administração & dosagem , Perileno/análogos & derivados , Fármacos Fotossensibilizantes/administração & dosagem , Acrilatos/química , Adesivos/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Humanos , Azul de Metileno/química , Neoplasias/tratamento farmacológico , Perileno/administração & dosagem , Perileno/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Poloxâmero/química , Temperatura
15.
Mar Drugs ; 18(1)2020 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-31963874

RESUMO

Five new perylenequinone derivatives, altertoxins VIII-XII (1-5), as well as one known compound cladosporol I (6), were isolated from the fermentation broth of the marine-derived fungus Cladosporium sp. KFD33 from a blood cockle from Haikou Bay, China. Their structures were determined based on spectroscopic methods and ECD spectra analysis along with quantum ECD calculations. Compounds 1-6 exhibited quorum sensing inhibitory activities against Chromobacterium violaceum CV026 with MIC values of 30, 30, 20, 30, 20 and 30 µg/well, respectively.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Cladosporium/química , Perileno/análogos & derivados , Quinonas/química , Percepção de Quorum/efeitos dos fármacos , China , Testes de Sensibilidade Microbiana/métodos , Naftalenos/química , Naftalenos/farmacologia , Perileno/química , Perileno/farmacologia , Quinonas/farmacologia
16.
ACS Appl Mater Interfaces ; 12(8): 9098-9106, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-31990177

RESUMO

In this work, a triple-amplified biosensor with a bioactivity-maintained peculiarity was constructed for quantitative procalcitonin (PCT) detection. As everyone knows, a strong electrochemiluminescence (ECL) signal is the premise to ensure high sensitivity for trace target detection. Hence, a valid tactic was developed to achieve signal amplification of luminophor by using Co2+-based metal-organic frameworks (ZIF-67) and silver-cysteine (AgCys). The ZIF-67 particles, which have more atomically dispersed Co2+, could play the role of a co-reaction accelerator to catalyze S2O82- to generate abundant Co3+ and sulfate radical anions (SO4•-). Afterward, a mass of Co3+ was reduced to more hydroxyl radicals (OH•) by H2O, thus ulteriorly reducing S2O82- to generate more SO4•-. Remarkably, S2O82- was reduced to SO4•- continuously with the recycling of Co2+ and Co3+, which realized an effective signal amplification. Meanwhile, the AgCys complex with superior catalysis and biocompatibility was prepared to further improve the ECL signal and maintain the bioactivity of the biomolecule. Furthermore, HWRGWVC, a heptapeptide that was used for combining the Fc fragments of an antibody by Au-S bonding to achieve the fixed point fixation, could not only maintain bioactivity of an antibody but also improved its incubation efficiency, thus further enhancing biosensor sensitivity. Under optimum conditions, the proposed biosensor realized highly sensitive assay for PCT with a wide dynamic range from 10 fg/mL to 100 ng/mL and a detection limit as low as 3.67 fg/mL. With superior stability, selectivity, and repeatability, the prepared biosensor revealed immense potential application of ultrasensitive assay for PCT in human serum.


Assuntos
Cobalto/química , Cisteína/química , Estruturas Metalorgânicas/química , Perileno , Pró-Calcitonina/análise , Prata/química , Humanos , Perileno/análogos & derivados , Perileno/química
17.
Chem Commun (Camb) ; 56(11): 1705-1708, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-31942910

RESUMO

We report ultrathin organic photovoltaic elements optimized to run photofaradaic reactions in biological conditions. We demonstrate concurrent oxygen reduction to hydrogen peroxide and glucose oxidation. The devices are powered by deep-red irradiation in the tissue transparency window. We utilize bilayers of phthalocyanine, acting as the light absorber, and perylene diimide, functioning as both electron-acceptor and the hydrogen peroxide evolution electrocatalyst. These heterojunction bilayers are stable when irradiated in simulated physiological conditions, producing photovoltages sufficient to simultaneously drive cathodic oxygen reduction to H2O2 and anodic oxidation of glucose. We find that optimization of the anode metal is critical for sustained photofaradaic reactivity. Our results demonstrate a robust "wet" thin film photovoltaic with potential for physiological applications where localized electrochemical manipulation is desired, in particular the delivery of reactive oxygen species.


Assuntos
Técnicas Eletroquímicas/métodos , Peróxido de Hidrogênio/síntese química , Imidas/química , Indóis/química , Perileno/análogos & derivados , Técnicas Eletroquímicas/instrumentação , Desenho de Equipamento , Glucose/química , Ouro/química , Imidas/efeitos da radiação , Indóis/efeitos da radiação , Luz , Membranas Artificiais , Oxirredução , Oxigênio/química , Perileno/química , Perileno/efeitos da radiação , Fotoquímica/métodos
18.
Chem Biodivers ; 17(1): e1900596, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31782894

RESUMO

Within Sicilian flora, the genus Hypericum (Guttiferae) includes 10 native species, the most popular of which is H. perforatum. Hypericum's most investigated active compounds belong to naphtodianthrones (hypericin, pseudohypericin) and phloroglucinols (hyperforin, adhyperforin), and the commercial value of the drug is graded according to its total hypericin content. Ethnobotanical sources attribute the therapeutic properties recognized for H. perforatum, also to other Hypericum species. However, their smaller distribution inside the territory suggests that an industrial use of such species, when collected from the wild, would result in an unacceptable depletion of their natural stands. This study investigated about the potential pharmacological properties of 48 accessions from six native species of Hypericum, including H. perforatum and five 'minor' species, also comparing, when possible, wild and cultivated sources. The variability in the content of active metabolites was remarkably high, and the differences within the species were often comparable to the differences among species. No difference was enlightened between wild and cultivated plants. A carefully planned cultivation of Hypericum seems the best option to achieve high and steady biomass yields, but there is a need for phytochemical studies, aimed to identify for multiplication the genotypes with the highest content of the active metabolites.


Assuntos
Hypericum/química , Perileno/análogos & derivados , Floroglucinol/análogos & derivados , Terpenos/química , Hypericum/metabolismo , Perileno/química , Perileno/metabolismo , Floroglucinol/química , Floroglucinol/metabolismo , Sicília , Especificidade da Espécie , Terpenos/metabolismo
19.
Chemistry ; 26(12): 2741-2748, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-31886910

RESUMO

To achieve a highly efficient, dual-state emission platform for picric acid (PA) detection and latent fingerprint (LFP) visualization, flexible alkyl chains have been facilely attached to the commercial organic dye 3,4,9,10-perylenetetracarboxylic dianhydride to provide the target perylenetetracarboxylate molecules PTCA-C4, PTCA-C6, and PTCA-C12. Interestingly, all these molecules exhibited impressive fluorescence characteristics with high photoluminescence quantum yields (PLQYs) of around 93.0 % in dilute solution. Also, emissive features were observed in the solid state because close molecular packing is prevented by the alkyl chains, especially for PTCA-C6, which has a high PLQY value of 49.0 %. Benefiting from its impressive fluorescence performance in both solution and as aggregates, PTCA-C6 was used as a dual-state emission platform for PA detection and also LFP visualization. For example, double-responsive fluorescence quenching in solution was observed in PA detection studies, resulting in high quenching constants (KSV ) and also low limit-of-detection values. Furthermore, the fingerprint powder based on PTCA-C6 also presented an impressive performance on various substrates in terms of fluorescence intensity and resolution, clearly providing the specific fine details of latent fingerprints. These results demonstrate that the facilely synthesized PTCA-C6 with efficient dual-state emission exhibits great potential in the real-world applications of PA detection and LFP visualization.


Assuntos
Anidridos/química , Dermatoglifia , Corantes Fluorescentes/síntese química , Perileno/análogos & derivados , Picratos/análise , Teoria da Densidade Funcional , Humanos , Limite de Detecção , Estrutura Molecular , Perileno/química , Espectrometria de Fluorescência
20.
Appl Microbiol Biotechnol ; 104(1): 211-223, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31768612

RESUMO

Hypocrellins, as natural pigments from Shiraia bambusicola, have extensive applications in the agricultural, cosmetic, food, and feed industries, and play a vital role in photodynamic therapy for anticancer and antiviral treatments. However, environmental stresses are always the bottlenecks for increasing hypocrellin yield during the process of fermentation. Pre-mRNA alternative splicing (AS) is an essential mechanism in the defense of abiotic stresses in the animal and plant kingdom, but is seldom involved in fungi. In this study, AS from genome-wide sequencing and RNA-seq data for S. bambusicola was analyzed for the first time. Interestingly, the proportion of AS in S. bambusicola was 38.44% (most of them participated in metabolic processes, covering pigmentation and response to stimulus), a much higher ratio than seen in that of other fungal species (1.3-18%). Here, we identified the relationship of AS and secondary metabolic (SM) biosynthesis under a series of abiotic stresses. Suitable fungicides suppressed hypocrellin production significantly, and AS occurred in key functional genes (sbFLO, sbMFS, sbPKS) of hypocrellin biosynthesis. In contrast, H2O2 improved the yield of hypocrellins, but AS were not found in the corresponding gene cluster. A further study showed that overexpressing an isoform of sbPKS (sbPKSa) in Shiraia bambusicola could dramatically down-regulate the expression of the original gene sbPKS and nearly inhibit the production of hypocrellins. Altogether, our study strongly supported the hypothesis that AS had a vital role in the regulation of hypocrellin biosynthesis under stresses, and initially explored whether SM functional genes were relevant for fungi.


Assuntos
Processamento Alternativo , Ascomicetos/genética , Vias Biossintéticas , Regulação Fúngica da Expressão Gênica , Perileno/análogos & derivados , Quinonas/metabolismo , Antifúngicos/farmacologia , Ascomicetos/efeitos dos fármacos , Fermentação , Peróxido de Hidrogênio/farmacologia , Família Multigênica , Perileno/metabolismo , Fenol , Metabolismo Secundário , Estresse Fisiológico
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