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1.
Chem Commun (Camb) ; 55(61): 8975-8978, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31290492
2.
Eur J Med Chem ; 178: 243-258, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31185414

RESUMO

To address the multifactorial nature of Alzheimer's Disease (AD), a multi-target-directed ligand approach was herein developed. As a follow-up of our previous studies, a small library of newly designed 2-arylbenzofuran derivatives was evaluated towards cholinesterases and cannabinoid receptors. The two most promising compounds, 8 and 10, were then assessed for their neuroprotective activity and for their ability to modulate the microglial phenotype. Compound 8 emerged as able to fight AD from several directions: it restored the cholinergic system by inhibiting butyrylcholinesterase, showed neuroprotective activity against Aß1-42 oligomers, was a potent and selective CB2 ligand and had immunomodulatory effects, switching microglia from the pro-inflammatory M1 to the neuroprotective M2 phenotype. Derivative 10 was a potent CB2 inverse agonist with promising immunomodulatory properties and could be considered as a tool for investigating the role of CB2 receptors and for developing potential immunomodulating drugs addressing the endocannabinoid system.


Assuntos
Benzofuranos/farmacologia , Inibidores da Colinesterase/farmacologia , Fatores Imunológicos/farmacologia , Fármacos Neuroprotetores/farmacologia , Bibliotecas de Moléculas Pequenas/farmacologia , Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/antagonistas & inibidores , Animais , Benzofuranos/síntese química , Benzofuranos/química , Benzofuranos/metabolismo , Butirilcolinesterase/química , Butirilcolinesterase/metabolismo , Células CHO , Domínio Catalítico , Linhagem Celular Tumoral , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Inibidores da Colinesterase/metabolismo , Cricetulus , Desenho de Drogas , Humanos , Fatores Imunológicos/síntese química , Fatores Imunológicos/química , Fatores Imunológicos/metabolismo , Camundongos , Microglia/efeitos dos fármacos , Simulação de Acoplamento Molecular , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/metabolismo , Fragmentos de Peptídeos/antagonistas & inibidores , Ligação Proteica , Receptor CB1 de Canabinoide/metabolismo , Receptor CB2 de Canabinoide/metabolismo , Bibliotecas de Moléculas Pequenas/síntese química , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/metabolismo
3.
Phytochemistry ; 164: 86-93, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31102999

RESUMO

Specialised metabolites in lichens are generally considered repellent compounds by consumers. Nevertheless, if the only food available is lichens rich in specialised metabolites, lichenophages must implement strategies to overcome the toxicity of these metabolites. Thus, the balance between phagostimulant nutrients and deterrent metabolites could play a key role in feeding preferences. To further understand lichen-gastropod interactions, we studied the feeding behaviour and consumption in Notodiscus hookeri, the land snail native to sub-Antarctic islands. The lichen Usnea taylorii was used because of its simple chemistry, its richness in usnic acid (specialised metabolite) and arabitol (primary metabolite) and its presence in snail habitats. Choice tests in arenas with intact lichens versus acetone-rinsed lichens were carried out to study the influence of specialised metabolites on snail behaviour and feeding preference. Simultaneously, usnic acid and arabitol were quantified and located within the lichen thallus using HPLC-DAD-MS and in situ imaging by mass spectrometry to assess whether their spatial distribution explained preferential snail grazing. No-choice feeding experiments, with the pure metabolites embedded in an artificial diet, defined a gradual gustatory response, from strong repellence (usnic acid) to high appetence (D-arabitol). This case study demonstrates that the nutritional activity of N. hookeri is governed by the chemical quality of the food and primarily by nutrient availability (arabitol), despite the presence of deterrent metabolite (usnic acid).


Assuntos
Benzofuranos/metabolismo , Caramujos/metabolismo , Álcoois Açúcares/metabolismo , Usnea/metabolismo , Animais , Benzofuranos/química , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas , Caramujos/química , Álcoois Açúcares/química , Usnea/química
4.
Eur J Med Chem ; 177: 1-11, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31128433

RESUMO

Cannabinoids as THC and the CB1 allosteric modulator CBD were reported to have antiproliferative activities with no reports for other CB1 allosteric modulators as the 5-chloroindole-2-carboxamide derivatives and their furan congeners. Based on the antiproliferative activity of two 5-chlorobenzofuran-2-carboxamide allosteric CB1 modulators, a series of novel derivatives was designed and synthesized. The synthesized compounds were tested in a cell viability assay using human mammary gland epithelial cell line (MCF-10A) where all the compounds exhibited no cytotoxic effects and more than 85% cell viability at a concentration of 50 µM. Some derivatives showed good antiproliferative activities against tumor cells as compounds 8, 15, 21 and 22. The most active compound 15 showed equipotent activity to doxorubicin. Compounds 7, 9, 15, 16, 21 and 22 increased the level of active caspase 3 by 4-8 folds, compared to the control cells in MCF-7 cell line and doxorubicin as a reference drug. Compounds 15 and 21, the most activecaspase-3 inducers, increase the levels of caspase 8 and 9 indicating activation of both intrinsic and extrinsic pathways and showed potent induction of Bax, down-regulation of Bcl-2 protein levels and over-expression of Cytochrome C levels in MCF-7 cell lines. Compound 15 exhibited cell cycle arrest at the Pre-G1 and G2/M phases in the cell cycle analysis of MCF-7 cell line. The drug Likeness profile of the synthesized compounds showed that all the compounds were predicted to have high oral absorption complying with different pharmacokinetics filters.


Assuntos
Antineoplásicos/farmacologia , Benzofuranos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacocinética , Apoptose/efeitos dos fármacos , Benzofuranos/síntese química , Benzofuranos/química , Benzofuranos/farmacocinética , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Desenho de Drogas , Ensaios de Seleção de Medicamentos Antitumorais , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Estrutura Molecular , Receptor CB1 de Canabinoide , Relação Estrutura-Atividade
5.
Chem Commun (Camb) ; 55(44): 6221-6224, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31080975

RESUMO

Triangeliphthalides A-D (1-4), four novel phthalide trimers with two new linkage styles, were isolated from Angelica sinensis, together with two related phthalide dimers (5-6). Their structures including absolute configurations were determined. The production mechanism of phthalide polymers was proposed, and their bioactivities were also evaluated.


Assuntos
Angelica sinensis/química , Benzofuranos/química , Biopolímeros/química , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Estrutura Molecular
6.
Fitoterapia ; 137: 104174, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31100437

RESUMO

Five new phthalide dimers, chaxiongnolides C-G (1-5), the two enantiomers of riligustilide (6a and 6b) and tokinolide B (7) were isolated from the aerial parts of Ligusticum sinense Oliv cv. Chaxiong. The structures of 1-5 were elucidated through extensive spectroscopic analysis, and the relative configurations of compounds 2 and 3 were further confirmed by an X-ray diffraction experiment. The absolute configurations of 1-3 were assigned by comparing calculated and experimental ECD spectra. The ECD exciton chirality method was used to confirm the absolute configurations of compounds 4, 5, 6a and 6b. Compounds 1-3 are the first dimeric phthalides to be reported that are comprising a sedanolide unit. The compounds were evaluated in vitro for their cytotoxic activity against select human cell lines.


Assuntos
Benzofuranos/química , Ligusticum/química , Benzofuranos/isolamento & purificação , Linhagem Celular , China , Humanos , Estrutura Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Componentes Aéreos da Planta/química , Estereoisomerismo , Difração de Raios X
7.
Forensic Sci Int ; 299: 89-94, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30981086

RESUMO

5-(2-ethylaminopropyl)benzofuran (5-EAPB) and 5,6-methylenedioxy-2-aminoindane (MDAI) are two new psychoactive substances (NPS) exhibiting MDMA-like properties. In this paper, we report the case of a 28-years old man, known as drug addict, found dead at home, with two unidentified powders next to him. External examination by the forensic pathologist was unremarkable but no autopsy was performed. Powders, blood and urine (which were the only samples available) were submitted to general unknown screening by high pressure liquid chromatography with a diode array detector (HPLC-DAD) and ultra high pressure liquid chromatography with a time-of-flight detector (UPLC-TOF-MS), after liquid-liquid extraction for biological samples, or simple dilution for powders. Analysis revealed 68% of MDAI in one powder and 87% of 5-EAPB in the other one. Significant levels of the same substances were found in blood (MDAI: 2.09 mg/L and 5-EAPB: 6.45 mg/L). The cause of death was therefore attributed to the consumption of these NPS since screening for other drugs of abuse and for alcohol was negative (oxazepam was found in urine only). 5-methylaminopropylbenzofuran (5-MAPB) and 5-aminopropylbenzofuran (5-APB) were also found in blood (0.089 and 0.546 mg/L, respectively) and urine (1.00 and 4.88 mg/L, respectively). In addition to the inherent complexity of NPS identification by itself, another analytical difficulty in this case was the identification of the EAPB positional isomer. Our routine screening methods were not able to distinguish the positional isomer, but an additional classical gas chromatography technique was able to make the distinction. Anyway, in our case, this issue was simplified thanks to the availability of a relatively pure powder that was analyzed by nuclear magnetic resonance (NMR).


Assuntos
Benzofuranos/envenenamento , Indanos/envenenamento , Psicotrópicos/envenenamento , Adulto , Benzofuranos/análise , Benzofuranos/química , Cromatografia Gasosa , Cromatografia Líquida de Alta Pressão , Humanos , Indanos/análise , Indanos/química , Espectroscopia de Ressonância Magnética , Masculino , Espectrometria de Massas , Estrutura Molecular , Psicotrópicos/análise , Psicotrópicos/química , Detecção do Abuso de Substâncias , Transtornos Relacionados ao Uso de Substâncias/complicações
8.
Biomed Chromatogr ; 33(8): e4561, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31017297

RESUMO

A sensitive and accurate LC-MS/MS method was established for quantifying salvianolic acid B (Sal B), rosmarinic acid (Ros A) and Danshensu (DA) in rat plasma. Salvia miltiorrhiza polyphenolic acid (SMPA), active water-soluble ingredients isolated and purified from Salvia miltiorrhiza Bge included Sal B, Ros A and DA. The pharmacokinetic analysis of Sal B, Ros A and DA after pulmonary administration of SMPA solution to rat was performed by LC-MS/MS. Results from the pharmacokinetic studies showed that the peak concentration of DA was 21.85 ± 6.43 and 65.39 ± 3.83 ng/mL after pulmonary and intravenous administration, respectively. DA was not detected at 2 h after administration. The absolute bioavailabilities of Sal B and Ros A were respectively 50.37 ± 27.04 and 89.63 ± 12.16% after pulmonary administration of 10 mg/kg SMPA solution in rats. The absolute bioavailability of Sal B increased at least 10-fold after pulmonary administration, compared with oral administration. It was concluded that the newly established LC-MS/MS method was suitable for describing the pharmacokinetic characteristics of Sal B, Ros A and DA in rat after pulmonary administration of SMPA solution. The data from this study will provide a preclinical insight into the feasibility of pulmonary administration of SMPA.


Assuntos
Benzofuranos/farmacocinética , Cinamatos/farmacocinética , Depsídeos/farmacocinética , Medicamentos de Ervas Chinesas/administração & dosagem , Lactatos/farmacocinética , Salvia miltiorrhiza , Administração por Inalação , Animais , Benzofuranos/sangue , Benzofuranos/química , Disponibilidade Biológica , Cromatografia Líquida , Cinamatos/sangue , Cinamatos/química , Depsídeos/sangue , Depsídeos/química , Estabilidade de Medicamentos , Lactatos/sangue , Lactatos/química , Limite de Detecção , Modelos Lineares , Masculino , Polifenóis , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos
9.
Molecules ; 24(7)2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30939842

RESUMO

A preparation process of salvianolic acid B (SAB) disodium salt from Salvia miltiorrhiza Bunge (Danshen) is provided in this work. A water extract quality standard was also developed to estimate the influences of Danshen quality on SAB disodium salt quality at an early stage of the preparation process. Crude SAB solution was obtained after water extraction, concentration, acidification, 1-butanol extraction, water washing, basification, and water back extraction. Extraction temperature, extraction pH, and back-extraction pH were identified to be key parameters for the preparation of crude SAB solution. These parameters were optimized with Box⁻Behnken designed experiments. Crude SAB solution was further purified with a chromatography process. AMBERCHROW CG161M resin was selected as the best adsorbent. SAB disodium salt could be obtained by drying the eluate. Considering the quality of Danshen may affect the purity and yield of SAB disodium salt, different batches of Danshen were used to prepare SAB disodium salt with the optimized parameters. Water extract indices of phenolic compound purity and phenolic compound yield were measured. By developing models between SAB disodium salt purity and yield with water extract indices, the quality standard of Danshen water extract was obtained. The application of water extract quality standards can improve the quality consistency of SAB disodium salt. The effects of different batches of Danshen raw materials on the final product could be evaluated at the beginning of production stages. The present method could prepare about five grams of high-purity SAB disodium salt (>95%) in one preparation cycle. The method reported in this work can also be used to develop process intermediate quality standards for other natural products.


Assuntos
Benzofuranos/isolamento & purificação , Benzofuranos/metabolismo , Extratos Vegetais/química , Salvia miltiorrhiza/química , Cloreto de Sódio/química , Água/química , Benzofuranos/química
10.
Molecules ; 24(8)2019 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-31003438

RESUMO

The results of our previous research indicated that some derivatives of benzofurans, particularly halogeno-derivatives, are selectively toxic towards human leukemia cells. Continuing our work with this group of compounds we here report new data on the synthesis as well as regarding the physico-chemical and biological characterization of fourteen new derivatives of benzofurans, including six brominated compounds. The structures of all new compounds were established by spectroscopic methods (1H- and, 13C-NMR, ESI MS), and elemental analyses. Their cytotoxicity was evaluated against K562 (leukemia), MOLT-4 (leukemia), HeLa (cervix carcinoma), and normal cells (HUVEC). Five compounds (1c, 1e, 2d, 3a, 3d) showed significant cytotoxic activity against all tested cell lines and selectivity for cancer cell lines. The SAR analysis (structure-activity relationship analysis) indicated that the presence of bromine introduced to a methyl or acetyl group that was attached to the benzofuran system increased their cytotoxicity both in normal and cancer cells.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Benzofuranos/síntese química , Benzofuranos/farmacologia , Antineoplásicos/química , Benzofuranos/química , Caspase 3/metabolismo , Caspase 7/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , DNA/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Concentração Inibidora 50
11.
Protein Pept Lett ; 26(5): 364-370, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30827223

RESUMO

BACKGROUND: Natural products are produced via primary and secondary metabolism in different organisms. The compounds obtained via secondary metabolism are not essential for the survival of the organism, but they can have a different value for humans. OBJECTIVE: The objective of this study was to examine inhibitory effects of Usnic Acid (UA), a well-known lichen secondary metabolite, and Carnosic Acid (CA), the primary antioxidant compound of Rosmarinus officinalis L., on purified Human Paraoxonase, (PON1), Glutathione Reductase (GR) and Glutathione S-Transferase (GST). These enzymes have antioxidant properties and a protective effect on the oxidation of free radicals. Hence, deficiencies of such enzymes inside cells can result in a buildup of toxic substances and cause some metabolic disorders. METHODS: UA and CA were tested in various concentrations against human GST, PON1, and GR activity in vitro and they reduced human GST, PON1, and GR activity. RESULTS: UA Ki constants were calculated as 0.012±0.0019, 0.107±0.06 and 0.21±0.1 mM for GST, PON1, and GR enzymes. CA Ki constants were determined as 0.028±0.009, 0.094±0.03 and 0.79±0.33 mM, for GST, PON1, and GR enzymes. UA and CA showed competitive inhibition for GR and GST enzymes, while they exhibited non-competitive inhibition for PON1. CONCLUSION: These findings indicate that UA and CA could be useful in drug development studies.


Assuntos
Antioxidantes/química , Arildialquilfosfatase/antagonistas & inibidores , Benzofuranos/química , Diterpenos de Abietano/química , Inibidores Enzimáticos/química , Glutationa Redutase/antagonistas & inibidores , Glutationa Transferase/antagonistas & inibidores , Arildialquilfosfatase/química , Glutationa Redutase/química , Glutationa Transferase/química , Humanos , Oxirredução , Rosmarinus
12.
Fitoterapia ; 134: 196-200, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30825579

RESUMO

Three undescribed 3(2H)-furanone derivatives, asperfuranones A-C (1-3), along with one known compound (4) were isolated from the Aspergillus sp. strain obtained from the intestines of centipede. Their structures were determined by NMR and MS spectroscopic analyses, and the absolute configurations were established by the Snatzke's sector rules, modified Mosher's method and electronic circular dichroism (ECD) calculation. Meanwhile, the application of the sector rules led to the reassignment of the absolute configurations of 4 and other seventeen previously reported analogues (5-21).


Assuntos
Aspergillus/química , Benzofuranos/química , Animais , Dicroísmo Circular , Camundongos , Estrutura Molecular , Células RAW 264.7
13.
Eur J Med Chem ; 166: 417-431, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30739824

RESUMO

Aurones are very simple, promising anticancer lead molecules containing three rings (A, B and C). A very slight structural variation in the aurones elicits diverse affinity and specificity towards different molecular targets. The present review discusses the design, discovery and development of natural and synthetic aurones as small molecule anticancer agents. Detailed structure-activity relationship and intermolecular interactions at different targets are also discussed. Due to their rare occurrence in nature and minimal mention in literature, the anticancer potential of aurones is rather recent but in constant progress.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Benzofuranos/química , Benzofuranos/farmacologia , Descoberta de Drogas/métodos , Animais , Humanos
14.
Mar Drugs ; 17(2)2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30717208

RESUMO

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases with a multifactorial nature. ß-Secretase (BACE1) and acetylcholinesterase (AChE), which are required for the production of neurotoxic ß-amyloid (Aß) and the promotion of Aß fibril formation, respectively, are considered as prime therapeutic targets for AD. In our efforts towards the development of potent multi-target, directed agents for AD treatment, major phlorotannins such as eckol, dieckol, and 8,8'-bieckol from Ecklonia cava (E. cava) were evaluated. Based on the in vitro study, all tested compounds showed potent inhibitory effects on BACE1 and AChE. In particular, 8,8'-bieckol demonstrated the best inhibitory effect against BACE1 and AChE, with IC50 values of 1.62 ± 0.14 and 4.59 ± 0.32 µM, respectively. Overall, kinetic studies demonstrated that all the tested compounds acted as dual BACE1 and AChE inhibitors in a non-competitive or competitive fashion, respectively. In silico docking analysis exhibited that the lowest binding energies of all compounds were negative, and specifically different residues of each target enzyme interacted with hydroxyl groups of phlorotannins. The present study suggested that major phlorotannins derived from E. cava possess significant potential as drug candidates for therapeutic agents against AD.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Ácido Aspártico Endopeptidases/antagonistas & inibidores , Inibidores da Colinesterase/farmacologia , Alga Marinha/química , Taninos/farmacologia , Proteína ADAM17/antagonistas & inibidores , Doença de Alzheimer/enzimologia , Benzofuranos/química , Benzofuranos/farmacologia , Colinesterases/química , Colinesterases/metabolismo , Dioxinas/química , Dioxinas/farmacologia , Simulação de Acoplamento Molecular , Taninos/química
15.
Int J Biol Macromol ; 128: 893-901, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30708006

RESUMO

Thymol and usnic acid as the important secondary metabolites of respectively Artemisia haussknechtii and Protoparmeliopsis muralis were used for reduction and stabilizing of AgNO3 and CuSO4 in metal nanoparticles (MNPs) biosynthesis process. Antibacterial effects of prepared Ag-thymol (ATNPs), Ag-usnic acid (AUNPs), Cu-thymol (CTNPs), and Cu-usnic acid (CUNPs) on multi drug resistant (MDR) bacteria including methicillin-resistant Staphylococcus aureus (MRSA) (gram positive), Acinetobacter baumannii (A52), and Klebsiella pneumonia (K38) (gram negative) were compared with thymol, usnic acid, AgNO3, CuSO4, and tetracycline. Results of this study showed higher antibacterial activities of usnic acid, CUNPs, and CTNPs with MIC/MBC values (20, 40, and 40 µg/mL, respectively) than ATNPs and AUNPs against MRSA bacteria. Leakage of macromolecules involving nucleic acids and proteins from bacteria under stress of MNPs, thymol, and usnic acid proved significant antibacterial activities of usnic acid, and Cu NPs. In addition, SEM images illustrated different patterns of aggregation in biofilms resulted from interactions of these antibacterial agents with bacterial macromolecules. Totally, this investigation illustrated new green method of Ag and Cu NPs biosynthesis with suitable antibacterial properties.


Assuntos
Antibacterianos/farmacologia , Benzofuranos/metabolismo , Cobre/química , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Nanopartículas Metálicas/química , Prata/química , Timol/metabolismo , Antibacterianos/síntese química , Antibacterianos/química , Benzofuranos/química , Biofilmes/efeitos dos fármacos , Técnicas de Química Sintética , Testes de Sensibilidade Microbiana , Timol/química
16.
Plant Physiol ; 179(4): 1822-1833, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30700538

RESUMO

Jasmonic acid (JA) plays an important role in the induction of herbivore resistance in many plants. However, JA-independent herbivore resistance has been suggested. An herbivore-resistance-inducing substance was isolated from Tobacco mosaic virus-infected tobacco (Nicotiana tabacum) leaves in which a hypersensitive response (HR) was induced and identified as loliolide, which has been identified as a ß-carotene metabolite. When applied to tomato (Solanum lycopersicum) leaves, loliolide decreased the survival rate of the two-spotted spider mite, Tetranychus urticae, egg deposition by the same pest, and the survival rate of larvae of the common cutworm Spodoptera litura without exhibiting toxicity against these herbivores. Endogenous loliolide levels increased not only with an infestation by S litura larvae, but also with the exogenous application of their oral secretions in tomato. A microarray analysis identified cell-wall-associated defense genes as loliolide-responsive tomato genes, and exogenous JA application did not induce the expression of these genes. Suppressor of zeaxanthin-less (szl), an Arabidopsis (Arabidopsis thaliana) mutant with a point mutation in a key gene of the ß-carotene metabolic pathway, exhibited the decreased accumulation of endogenous loliolide and increased susceptibility to infestation by the western flower thrip (Frankliniella occidentalis). A pretreatment with loliolide decreased susceptibility to thrips in the JA-insensitive Arabidopsis mutant coronatine-insensitive1 Exogenous loliolide did not restore reduced electrolyte leakage in szl in response to a HR-inducing bacterial strain. These results suggest that loliolide functions as an endogenous signal that mediates defense responses to herbivores, possibly independently of JA, at least in tomato and Arabidopsis plants.


Assuntos
Benzofuranos/metabolismo , Herbivoria , Tabaco/química , Animais , Arabidopsis/efeitos dos fármacos , Benzofuranos/química , Benzofuranos/isolamento & purificação , Carotenoides/metabolismo , Morte Celular , Lycopersicon esculentum/efeitos dos fármacos , Lycopersicon esculentum/parasitologia , Spodoptera/fisiologia , Tetranychidae/fisiologia , Tabaco/virologia , Vírus do Mosaico do Tabaco
17.
Biomolecules ; 9(2)2019 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-30704099

RESUMO

Human nosocomial infections are common around the world. One of the main causes is the bacteria Klebsiella pneumoniae, which shows high rates of resistance to antibiotics. Thus, drugs with novel mechanisms of action are needed. In this work, we report the effects of various natural substances on the formation of biofilm in Klebsiella pneumoniae, as well as its stability. The effect of the molecules on the growth of K. pneumoniae was initially determined by measuring the optical density. The modification of the biofilm, the changes relating to its resistance, the effects on the bacterial adhesion to the urethral catheter and its antagonist role the hexanoyl-homoserinelactone were assessed by crystal violet, as well as by microscopy. The best effects were obtained with 3-methyl-2(5H)-furanone and 2´-hydroxycinnamic acid, which inhibited the formation of biofilm by 67.38% and 65.06%, respectively. Additionally, the remaining biofilm formed was more susceptible to gentamicin. Through microscopy examination, there were evident changes in the biofilm and adherence on the polyvinyl chloride (PVC) urethral catheter. Besides, 3-methyl-2(5H)-furanone inhibited the biofilm-forming effect of the autoinducer hexanoyl-homoserinelactone. Thus, these molecules could be developed as supplemental of antibiotics.


Assuntos
Antibacterianos/farmacologia , Benzofuranos/farmacologia , Biofilmes/efeitos dos fármacos , Produtos Biológicos/farmacologia , Ácidos Cumáricos/farmacologia , Klebsiella pneumoniae/efeitos dos fármacos , Antibacterianos/química , Benzofuranos/química , Biofilmes/crescimento & desenvolvimento , Produtos Biológicos/química , Sobrevivência Celular/efeitos dos fármacos , Ácidos Cumáricos/química , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade
18.
Exp Mol Med ; 51(2): 10, 2019 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-30755586

RESUMO

Hypoxia-inducible factor-1α (HIF-1α) mediates tumor cell adaptation to hypoxic conditions and is a potentially important anticancer therapeutic target. We previously developed a method for synthesizing a benzofuran-based natural product, (R)-(-)-moracin-O, and obtained a novel potent analog, MO-460 that suppresses the accumulation of HIF-1α in Hep3B cells. However, the molecular target and underlying mechanism of action of MO-460 remained unclear. In the current study, we identified heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) as a molecular target of MO-460. MO-460 inhibits the initiation of HIF-1α translation by binding to the C-terminal glycine-rich domain of hnRNPA2B1 and inhibiting its subsequent binding to the 3'-untranslated region of HIF-1α mRNA. Moreover, MO-460 suppresses HIF-1α protein synthesis under hypoxic conditions and induces the accumulation of stress granules. The data provided here suggest that hnRNPA2B1 serves as a crucial molecular target in hypoxia-induced tumor survival and thus offer an avenue for the development of novel anticancer therapies.


Assuntos
Benzofuranos/farmacologia , Produtos Biológicos/farmacologia , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/antagonistas & inibidores , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Regiões 3' não Traduzidas , Benzofuranos/química , Produtos Biológicos/química , Linhagem Celular Tumoral , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Estrutura Molecular , Ligação Proteica , Biossíntese de Proteínas/efeitos dos fármacos , Domínios e Motivos de Interação entre Proteínas , Estresse Fisiológico/efeitos dos fármacos , Transcrição Genética
19.
Org Lett ; 21(6): 1583-1587, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30799624

RESUMO

A pair of enantiomeric triketone-phloroglucinol hybrids, (+)- and (-)-myrtuspirone A (1), featuring an unprecedented 3-isopropyl-3 H-spiro[benzofuran-2,1'-cyclohexane] backbone, were isolated from the leaves of Myrtus communis. The absolute configuration of each enantiomer of 1 was determined by X-ray diffraction and chemical calculations. Furthermore, the gram-scale total syntheses of (±)-1 and (-)-1 were conducted in four steps using a Michael- N-iodosuccinimide (NIS)-mediated (3 + 2)-annulation reaction. Both (+)- and (-)-1 exhibited antibacterial activities against Gram-positive bacteria including multidrug-resistant strains.


Assuntos
Antibacterianos , Benzofuranos , Cicloexanos/química , Bactérias Gram-Positivas/efeitos dos fármacos , Myrtus/química , Folhas de Planta/química , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Benzofuranos/síntese química , Benzofuranos/química , Benzofuranos/farmacologia , Estrutura Molecular , Floroglucinol/química , Estereoisomerismo
20.
Pharmazie ; 74(2): 67-72, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30782253

RESUMO

Psoralidin, a prenylated coumestrol isolated from the seed of a traditional Chinese medicine Psoralea corylifolia L., has been demonstrated to exhibit anti-inflammatory, anti-cancer, anti-oxidative, estrogenic, neuroprotective, anti-bacterial, and anti-parasite activities. Due to prenylation, psoralidin exhibits stronger estrogenic activity with no obvious adverse effects and shows a close association with management of osteoporosis and some cancers. However, the hydrophobicity and low bioavailability of psoralidin limit its clinical application, although recent investigation has gained valuable data. This review will discuss the biological activities of psoralidin in health.


Assuntos
Benzofuranos/farmacologia , Cumarínicos/farmacologia , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Benzofuranos/química , Benzofuranos/uso terapêutico , Cumarínicos/química , Cumarínicos/uso terapêutico , Estrogênios/química , Estrogênios/farmacologia , Estrogênios/uso terapêutico , Humanos , Redes e Vias Metabólicas/efeitos dos fármacos , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
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