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1.
Nature ; 584(7819): 75-81, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32760044

RESUMO

Chemical reactions that reliably join two molecular fragments together (cross-couplings) are essential to the discovery and manufacture of pharmaceuticals and agrochemicals1,2. The introduction of amines onto functionalized aromatics at specific and pre-determined positions (ortho versus meta versus para) is currently achievable only in transition-metal-catalysed processes and requires halogen- or boron-containing substrates3-6. The introduction of these groups around the aromatic unit is dictated by the intrinsic reactivity profile of the method (electrophilic halogenation or C-H borylation) so selective targeting of all positions is often not possible. Here we report a non-canonical cross-coupling approach for the construction of anilines, exploiting saturated cyclohexanones as aryl electrophile surrogates. Condensation between amines and carbonyls, a process that frequently occurs in nature and is often used by (bio-)organic chemists7, enables a predetermined and site-selective carbon-nitrogen (C-N) bond formation, while a photoredox- and cobalt-based catalytic system progressively desaturates the cyclohexene ring en route to the aniline. Given that functionalized cyclohexanones are readily accessible with complete regiocontrol using the well established carbonyl reactivity, this approach bypasses some of the frequent selectivity issues of aromatic chemistry. We demonstrate the utility of this C-N coupling protocol by preparing commercial medicines and by the late-stage amination-aromatization of natural products, steroids and terpene feedstocks.


Assuntos
Compostos de Anilina/síntese química , Hidrogênio/química , Processos Fotoquímicos , Aminação , Aminas/química , Compostos de Anilina/química , Produtos Biológicos/síntese química , Produtos Biológicos/química , Catálise/efeitos da radiação , Cicloexanonas/química , Oxirredução/efeitos da radiação , Processos Fotoquímicos/efeitos da radiação , Esteroides/síntese química , Esteroides/química , Terpenos/síntese química , Terpenos/química
2.
Chem Biol Interact ; 330: 109165, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32771326

RESUMO

The effect of N-geranyl-ethane-1,2-diamine dihydochloride (GIB24), a synthetic diamine, was assayed against different developmental forms of the parasitic protozoan Trypanosoma cruzi (strain Dm28c). The compound was effective against culture epimastigote forms (IC50/24h = 5.64 µM; SI = 16.4) and intracellular amastigotes (IC50/24h = 12.89 µM; SI = 7.18), as detected by the MTT methodology and by cell counting, respectively. Incubation of epimastigotes for 6h with 6 µM GIB24 (IC50/24h value) resulted in significant dissipation of the mitochondrial membrane potential, prior to permeabilization of the plasma membrane. Rounded epimastigotes with cell size reduction were observed by scanning electron microscopy. These morpho-physiological changes induced by GIB24 suggest an incidental death process. Treatment of infected Vero cells did not prevent the intracellular amastigotes from completing the intracellular cycle. However, there was a decrease in the number of released parasites, increasing the ratio amastigotes/trypomastigotes. Proteomic analysis of 15 µM GIB24 resistant epimastigotes indicated that the compound acts mainly on mitochondrial components involved in the Krebs cycle and in maintaining the oxidative homeostasis of the parasites. Our data suggest that GIB24 is active against the main morphological forms of T. cruzi.


Assuntos
Diaminas/farmacologia , Resistência a Medicamentos , Espaço Intracelular/efeitos dos fármacos , Proteômica , Terpenos/química , Trypanosoma cruzi/efeitos dos fármacos , Trypanosoma cruzi/crescimento & desenvolvimento , Animais , Chlorocebus aethiops , Diaminas/química , Espaço Intracelular/parasitologia , Tripanossomicidas/química , Tripanossomicidas/farmacologia , Trypanosoma cruzi/metabolismo , Células Vero
3.
Braz Oral Res ; 34: e050, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32578760

RESUMO

Candida infection is an important cause of morbidity and mortality in immunocompromised patients. The increase in its incidence has been associated with resistance to antimicrobial therapy and biofilm formation. The aim of this study was to evaluate the efficacy of tea tree oil (TTO) and its main component - terpinen-4-ol - against resistant Candida albicans strains (genotypes A and B) identified by molecular typing and against C. albicans ATCC 90028 and SC 5314 reference strains in planktonic and biofilm cultures. The minimum inhibitory concentration, minimum fungicidal concentration, and rate of biofilm development were used to evaluate antifungal activity. Results were obtained from analysis of the biofilm using the cell proliferation assay 2,3-Bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) and confocal laser scanning microscopy (CLSM). Terpinen-4-ol and TTO inhibited C. albicans growth. CLSM confirmed that 17.92 mg/mL of TTO and 8.86 mg/mL of terpinen-4-ol applied for 60 s (rinse simulation) interfered with biofilm formation. Hence, this in vitro study revealed that natural substances such as TTO and terpinen-4-ol present promising results for the treatment of oral candidiasis.


Assuntos
Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Óleo de Melaleuca/farmacologia , Terpenos/farmacologia , Resinas Acrílicas , Análise de Variância , Antifúngicos/farmacologia , Biofilmes/crescimento & desenvolvimento , Candida albicans/crescimento & desenvolvimento , Bases de Dentadura/microbiologia , Testes de Sensibilidade Microbiana , Microscopia Confocal , Valores de Referência , Reprodutibilidade dos Testes , Estatísticas não Paramétricas , Óleo de Melaleuca/química , Terpenos/química
4.
J Food Sci ; 85(7): 2032-2040, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32567698

RESUMO

Terpene glycosides (TGs) in the berry skins of Ecolly and Cabernet Gernischet (CG) grapes were profiled by ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and compared to that of Muscat Hamburg (MH) grapes. The aroma glycosides in grape skins were extracted by methanol, purified using Amberlite XAD-2 resins, eluted in methanol/ethyl acetate, and analyzed by UPLC-Q-TOF-MS. MS/MS fragmentation and the TG database were used for identification, while semiquantification was achieved by the internal standard, octyl-ß-D-glucopyranoside. Seven, nine, and thirteen TGs were identified in Ecolly, CG, and MH, respectively, whereas only four TGs were detected in all the varieties. Compared to MH, linalool-3-O-α-L-arabinofuranosyl-ß-D-glucopyranoside was unique for Ecolly, and pyran linalool oxide-α-L-arabinofuranosyl-ß-D-glucopyranoside was unique for CG. Furthermore, the total concentrations of TGs were 7.32, 3.50, and 81.27 mg/kg in Ecolly, CG, and MH, respectively. Diendiol I-α-D-apiofuranosyl-ß-D-glucopyranoside, furanosyl-linalool oxide-7-O-α-L-arabinofuranosyl-ß-D-glucopyranoside, and nerol-l-O-α-D-apiofuranosyl-ß-D-glucopyranoside were most abundant in Ecolly, CG, and MH, respectively. PRACTICAL APPLICATION: Terpene glycosides (TGs) are important aroma precursors for wines and it is meaningful to reveal the profiles of TGs in grapes. By analyzing the differences of TGs among the Ecolly, Cabernet Gernischet (CG), and Muscat Hamburg grape varieties, it is expected to provide guidance for the study on the aroma characteristics and aroma enhancing brewing of Ecolly and CG grapes. The results may provide technical experience on aroma glycoside identification and their quantification in grapes and wines for future studies.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Glicosídeos/química , Espectrometria de Massas em Tandem/métodos , Terpenos/química , Vitis/química , Vinho/análise , Frutas/química , Odorantes/análise
5.
J Chromatogr A ; 1621: 461044, 2020 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-32273090

RESUMO

The presented paper is the first to show thin layer chromatography (TLC) analysis based on eutectic mobile phases (Deep Eutectic Solvents - DES). During the experiment 25 eutectic mixtures were investigated for their chromatographic properties. Most of them belong to the natural deep eutectic solvents (NADES) group. Also, new eutectic liquids based on phenolics and terpenes, not previously employed in analytical practice, were tested. The eutectic liquids were investigated as pure or diluted with solvents used in chromatographic routine: methanol, water, acetone, chloroform or diethyl ether. The analyses were carried out using classic and high performance silica gel plates. The working solution was a mixture of five alkaloids found in genus Chelidonium, namely sanguinarine, coptisine, chelerythrine, chelidonine, and berberine, with UV light detection of 366 nm. This report proves that eutectic TLC is possible and that the eutectic interactions play a crucial role in the separation process. In most of the tested modifications at least partial separation was achieved. The most successful mobile phase, which enabled separation of all the tested alkaloids, was the equimolar mixture of menthol and phenol with a 35% addition of methanol. The system was also effective in separating alkaloids in the real Chelidonium maius extract sample.


Assuntos
Cromatografia em Camada Delgada/métodos , Alcaloides/análise , Chelidonium/química , Fenóis/química , Extratos Vegetais/química , Solventes/química , Terpenos/química
6.
Food Chem ; 320: 126608, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32229396

RESUMO

The postharvest ripening behaviour of mangoes (Mangifera indica L.) and particularly the development of colour, volatiles, sensory properties and texture, were investigated. Mangoes cv. Kent from Peru were arranged in a postharvest ripening chamber in two different ways enabling different ventilation of the fruits. Fruit properties were investigated in comparison to reference fruits after postharvest ripening for 78 h. Volatile compounds were analysed by HS-SPME GC-MS; an expert panel performed sensory analysis using descriptive methods. The arrangement of the mangoes significantly impacted the ripening procedures. Dense fruit arrangement induced a degradation of terpenes, a reduced formation of reaction products from the lipoxygenase pathway and less pronounced fruitiness and mango flavour. Principal component analysis based on volatile compounds and sensory properties showed a high correlation with the position in the ripening chamber. These data demonstrate the urgent need for further investigations of the postharvest ripening processes to increase mango quality.


Assuntos
Aromatizantes/análise , Frutas/química , Mangifera/química , Compostos Orgânicos Voláteis/análise , Manipulação de Alimentos , Cromatografia Gasosa-Espectrometria de Massas , Peru , Paladar , Terpenos/análise , Terpenos/química , Terpenos/metabolismo
7.
Adv Exp Med Biol ; 1260: 283-296, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32304038

RESUMO

In our society, anxiety and depression are serious health issues that affect a large proportion of the population. Unfortunately, drug therapies are not always effective and can lead to drug abuse, delay of therapeutic effect, dependence, and tolerance. Traditionally, aromatherapy has also been used for anxiety relief and mood improvement. The use of essential oils, in relieving anxiety and depression, does not have the disadvantages associated with currently used drug therapies. In-vivo studies on animal models have verified the anxiolytic effects of these essential oils and the interactions of their major components with central nervous system receptors. Therefore, it seems reasonable to argue that the modulation of glutamate and GABA neurotransmitter systems are likely to be the critical mechanisms responsible for the sedative, anxiolytic, and anticonvulsant proprieties of linalool and essential oils containing linalool in significant proportions. Popular anxiolytic essential oils are generally rich in terpenoid alcohols like linalool, geraniol and citronellol, and the monoterpene limonene (or citral). Therefore, other essential oils or formulations that contain these terpenoids as major components may serve as important aromatherapeutics for relief of anxiety.


Assuntos
Ansiolíticos/uso terapêutico , Ansiedade/tratamento farmacológico , Aromaterapia , Depressão/tratamento farmacológico , Óleos Voláteis/uso terapêutico , Terpenos/uso terapêutico , Animais , Ansiolíticos/química , Ansiolíticos/farmacologia , Anticonvulsivantes/química , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Humanos , Hipnóticos e Sedativos/química , Hipnóticos e Sedativos/farmacologia , Hipnóticos e Sedativos/uso terapêutico , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Terpenos/química , Terpenos/farmacologia
8.
Mar Drugs ; 18(4)2020 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-32290492

RESUMO

The anti-inflammatory and anticancer properties of eight meroterpenoids isolated from the brown seaweed Cystoseira usneoides have been evaluated. The algal meroterpenoids (AMTs) 1-8 were tested for their inhibitory effects on the production of the pro-inflammatory cytokines tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß), and the expression of cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) in LPS-stimulated THP-1 human macrophages. The anticancer effects were assessed by cytotoxicity assays against human lung adenocarcinoma A549 cells and normal lung fibroblastic MRC-5 cells, together with flow cytometry analysis of the effects of these AMTs on different phases of the cell cycle. The AMTs 1-8 significantly reduced the production of TNF-α, IL-6, and IL-1ß, and suppressed the COX-2 and iNOS expression, in LPS-stimulated cells (p < 0.05). The AMTs 1-8 displayed higher cytotoxic activities against A549 cancer cells than against MRC-5 normal lung cells. Cell cycle analyses indicated that most of the AMTs caused the arrest of A549 cells at the G2/M and S phases. The AMTs 2 and 5 stand out by combining significant anti-inflammatory and anticancer activities, while 3 and 4 showed interesting selective anticancer effects. These findings suggest that the AMTs produced by C. usneoides may have therapeutic potential in inflammatory diseases and lung cancer.


Assuntos
Anti-Inflamatórios/química , Antineoplásicos/química , Organismos Aquáticos , Feófitas , Terpenos/química , Células A549/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Citocinas/efeitos dos fármacos , Humanos , Terpenos/farmacologia
9.
Food Chem ; 320: 126632, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32217431

RESUMO

Precise identification of the compounds characteristic to stored white teas is urgently needed as these products have unique flavors and health benefits that improve with storage duration. Owing to the potential applications in food quality discrimination, specific regularities between the enantiomeric distributions of 23 volatile lactones and terpenoids and storage durations of white teas were expected and investigated by enantioselective gas chromatography-mass spectrometry (Es-GC-MS) combined with multivariate statistical analysis. High correlation coefficients (-0.853 to 0.695) and significant differences (P < 0.001) between the enantiomeric ratios (ERs) of (2S, 5S)-linalool oxide A, (2S, 5R)-linalool oxide B, (2R, 5S)-theaspirane B, S-linalool, and (1R, 2S)-methyl epijasmonate and the storage durations (0-7 years) were obtained, and the contents of S-linalool and S/R-dihydroactinidiolide significantly decreased and increased, respectively, with the increasing of storage duration. Therefore, the aforementioned lactone and terpenoid enantiomers are potential markers for the reliable differentiation of white teas stored for different time periods.


Assuntos
Lactonas/química , Extratos Vegetais/química , Chá/química , Terpenos/química , Cromatografia Gasosa-Espectrometria de Massas , Estereoisomerismo
10.
Int J Syst Evol Microbiol ; 70(4): 2602-2610, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32160142

RESUMO

A novel Gram-stain-positive, aerobic, motile with peritrichous flagella, rod-shaped bacterium, designated CC-MHH1044T, was isolated from a preserved vegetable sample. A polyphasic taxonomic approach was applied to the isolates in order to clarify its taxonomic position. Growth of the strain CC-MHH1044T occurred at 15-50 °C (optimum, 30 °C), pH 6.0-8.0 (optimum, pH 7.0) and with 0-2.0 % (w/v) NaCl (optimum, 1 %, w/v). The genome of strain CC-MHH1044T consisted of 8.5 Mb and the genomic DNA G+C content was 58.5 mol%. Comparison of the 16S rRNA gene sequences showed that CC-MHH1044T belonged to the genus Cohnella and showed a close relationship with the type strains of Cohnella damuensis (96.2 %) and Cohnella panacarvi (95.9 %), and lower sequence similarity to other species. Average nucleotide identity values calculated from whole-genome sequencing data proved that CC-MHH1044T represents a distinct Cohnella species. The dominant cellular fatty acids (>5 %) included iso-C14 : 0(7.4 %), iso-C15 : 0 (6.4 %), anteiso-C15 : 0(40.3 %), C16 : 0 (6.6 %) and iso-C16 : 0 (27.0 %). The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, four unidentified aminophospholipids, one unidentified phospholipid and glycolipid. The major polyamine was spermidine. The predominant isoprenoid quinone was menaqinone 7 (MK-7). Based on its distinct phylogenetic, phenotypic and chemotaxonomic traits, together with results of comparative 16S rRNA gene sequence, average nucleotide identity and digital DNA-DNA hybridization analyses, we conclude that strain CC-MHH1044T represents a novel member of the genus Cohnella, for which the name Cohnella fermenti sp. nov. is proposed. The type strain is CC-MHH1044T (=BCRC 81147T=JCM 32834T).


Assuntos
Bacillales/classificação , Fermentação , Alimentos e Bebidas Fermentados/microbiologia , Filogenia , Bacillales/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Microbiologia de Alimentos , Glicolipídeos/química , Naftóis/química , Hibridização de Ácido Nucleico , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Taiwan , Terpenos/química , Sequenciamento Completo do Genoma
11.
Chem Commun (Camb) ; 56(22): 3329-3332, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32083260

RESUMO

Taxodisones A and B, C30-terpenes with an unprecedented tetracyclo[12.4.0.0.2,709,14]octodecane core, were isolated from the seeds of Taxodium distichum. Their structures, including their configurations, were unambiguously determined. Their biomimetic synthesis suggests that they stem from diterpenes and monoterpenes, and not from squalene or oxidosqualene. In addition, their bioactivities were also evaluated.


Assuntos
Diterpenos/química , Taxodium/química , Biomimética , Catálise , Complexos de Coordenação/química , Cristalografia por Raios X , Reação de Cicloadição , Diterpenos/metabolismo , Érbio/química , Conformação Molecular , Sementes/química , Sementes/metabolismo , Taxodium/metabolismo , Terpenos/química , Terpenos/metabolismo
12.
Biochem Biophys Res Commun ; 524(3): 772-783, 2020 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-32037088

RESUMO

This review is devoted to comparative pharmacological analysis of synthetic drugs such as memantine and its isomers, as well as tacrine, velnacrine, rivastigmine, and donepezil, with natural alkaloids, terpenoids, and triterpenoid peroxides, which are used to treat dementia, Alzheimer's and Parkinson's diseases, myasthenia gravis and other neurodegenerative diseases. Recently discovered by French scientists from Marseille triterpenoid hydroperoxides demonstrate high activity as potential therapeutic agents for the treatment of dementia. The information presented in this review is of great interest to pharmacologists, medical chemists, physiologists, neurologists and doctors, as well as for the pharmaceutical industry.


Assuntos
Produtos Biológicos/uso terapêutico , Demência/tratamento farmacológico , Medicamentos Sintéticos/uso terapêutico , Alcaloides/química , Alcaloides/uso terapêutico , Animais , Produtos Biológicos/química , Demência/prevenção & controle , Humanos , Medicamentos Sintéticos/química , Terpenos/química , Terpenos/uso terapêutico
13.
Int J Nanomedicine ; 15: 275-300, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32021180

RESUMO

Gold nanoparticles (AuNPs) are extensively studied nanoparticles (NPs) and are known to have profound applications in medicine. There are various methods to synthesize AuNPs which are generally categorized into two main types: chemical and physical synthesis. Continuous efforts have been devoted to search for other more environmental-friendly and economical large-scale methods, such as environmentally friendly biological methods known as green synthesis. Green synthesis is especially important to minimize the harmful chemical and toxic by-products during the conventional synthesis of AuNPs. Green materials such as plants, fungi, microorganisms, enzymes and biopolymers are currently used to synthesize various NPs. Biosynthesized AuNPs are generally safer for use in biomedical applications since they come from natural materials themselves. Multiple surface functionalities of AuNPs allow them to be more robust and flexible when combined with different biological assemblies or modifications for enhanced applications. This review focuses on recent developments of green synthesized AuNPs and discusses their numerous biomedical applications. Sources of green materials with successful examples and other key parameters that determine the functionalities of AuNPs are also discussed in this review.


Assuntos
Ouro/química , Química Verde/métodos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Animais , Bactérias/química , Sistemas de Liberação de Medicamentos , Fungos/química , Humanos , NAD/química , Fenóis/química , Plantas/química , Proteínas/química , Terpenos/química
14.
Molecules ; 25(3)2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32041149

RESUMO

Plant phytochemicals have potential decontaminating properties, however, their role in the amelioration of hydrophobic water filtration membranes have not been elucidated yet. In this work, phytochemicals (i.e., cannabinoids (C) and terpenes (T) from C. sativa) were revealed for their antibacterial activity against different Gram-positive and Gram-negative bacteria. As such, a synergistic relationship was observed between the two against all strains. These phytochemicals individually and in combination were used to prepare polyethersulfone (PES) hybrid membranes. Membrane characterizations were carried out using scanning electron microscopy, Fourier transform infrared spectroscopy, energy-dispersive X-ray spectroscopy. Moreover, contact angle, water retention, surface roughness, mechanical testing, and X-ray florescence analysis were also carried out. According to results, the CT-PES hybrid membrane exhibited the lowest contact angle (40°), the highest water retention (70%), and smallest average pore size (0.04 µm). The hybrid membrane also exhibited improved water flux with no surface leaching. Quantitative bacterial decline analysis of the CT-PES hybrid membranes confirmed an effective antibacterial performance against Gram-positive and Gram-negative bacteria. The results of this study established cannabinoids and terpenes as an inexpensive solution for PES membrane surface modification. These hybrid membranes can be easily deployed at an industrial scale for water filtration purposes.


Assuntos
Antibacterianos/farmacologia , Canabinoides/farmacologia , Terpenos/farmacologia , Antibacterianos/química , Canabinoides/química , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Membranas Artificiais , Microscopia Eletrônica de Varredura , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Polímeros , Sulfonas , Terpenos/química , Purificação da Água/instrumentação
15.
Org Lett ; 22(4): 1336-1339, 2020 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-32037840

RESUMO

Aspermeroterpene A (1) with an unprecedented and highly congested 5/3/6/6/6/5 hexacyclic skeleton, together with two precursors aspermeroterpenes B (2) and C (3), were isolated from the marine-derived fungus Aspergillus terreus GZU-31-1. Their structures were elucidated by quantum chemical calculations, X-ray diffraction, and spectroscopic methods. The biogenetic pathway for 1-3 is proposed. Aspermeroterpenes A-C (1-3) showed significant inhibitory activities against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 cells compared to positive control.


Assuntos
Aspergillus/química , Terpenos/farmacologia , Animais , Cristalografia por Raios X , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Camundongos , Modelos Moleculares , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Células RAW 264.7 , Terpenos/química , Terpenos/isolamento & purificação
16.
Org Biomol Chem ; 18(7): 1232-1278, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-31930246

RESUMO

The natural occurrence of enantiomers and diastereomers is often encountered. In addition, the synthesis of these stereoisomers is important for structure determination and for the study of structure-activity relationships. Stereodivergent routes simplify the access to these molecules starting from a common material. This review is focused on the synthesis of carbohydrates, amino acids, alkaloids and terpenes using this efficient strategy. In the case of carbohydrates, such as monosaccharides, carbasugars, aminosugars and azasugars, carbohydrates are usually employed as common starting materials. As a very common strategy, configurations of hydroxy groups are inverted by SN2 methods playing with protection and deprotection processes. For the synthesis of acyclic α-AAs, diastereoselective methods using mainly Garner's aldehyde have been described. Diastereodivergent routes allowed the synthesis of ß-hydroxy- and ß-amino-α-amino acids, as well as of ß- and γ-amino acids. Heterocyclic and cyclic amino phosphonic acids were synthesized using diastereodivergent routes. Alkaloids containing five- and six-membered saturated azaheterocycles needed multistep stereodivergent routes and other alkaloids, such as enantiomers of balanol, vincamine, anatoxin and codeine, and diastereomeric isochaetominines C and galanthamines. In the terpene field, sesquiterpenes ß-santalene, α-curcumene and α-cuparenone and the diterpene scopadulcic acid A have been synthesized using enantiodivergent routes.


Assuntos
Alcaloides/síntese química , Aminoácidos/síntese química , Carboidratos/síntese química , Terpenos/síntese química , Alcaloides/química , Aminoácidos/química , Carboidratos/química , Estrutura Molecular , Estereoisomerismo , Terpenos/química
17.
Org Biomol Chem ; 18(6): 1135-1139, 2020 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-31967630

RESUMO

Biomimetic total syntheses of baefrutones A-D (1-4), baeckenon B (5), and frutescones A, D-F (6-9), isolated from the leaves of Baeckea frutescens, were achieved in 9, 8, and 5 steps, respectively, in moderate to good yields (72-83%). The synthetic routes feature the Michael addition, oxidative [4 + 2] cycloaddition, and water-promoted Diels-Alder click reactions as the key steps. This study helped gain thorough mechanistic insights into the biosynthetic origins and provided a facile approach for the construction of a library of natural tasmanone-based meroterpenoid analogues. Moreover, compounds 1-9 show potent inhibitory effects against S. paratyphi and/or C. albicans with MIC values of 3.125-25 µg mL-1, and they could be promising lead molecules for the design of new antibiotic agents.


Assuntos
Materiais Biomiméticos/farmacologia , Monoterpenos/farmacologia , Terpenos/farmacologia , Materiais Biomiméticos/síntese química , Materiais Biomiméticos/química , Candida albicans/efeitos dos fármacos , Reação de Cicloadição , Teoria da Densidade Funcional , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Estrutura Molecular , Monoterpenos/síntese química , Monoterpenos/química , Oxirredução , Pseudomonas aeruginosa/efeitos dos fármacos , Salmonella/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Estereoisomerismo , Relação Estrutura-Atividade , Terpenos/síntese química , Terpenos/química
18.
Molecules ; 25(2)2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31936396

RESUMO

BACKGROUND: Natural meroterpenes derived from phloroglucinols and ß-caryophyllene have shown high inhibitory activity against α-glucosidase or cancer cells, however, the chemical diversity of this type of skeletons in Nature is limited. METHODS: To expand the chemical space and explore their inhibitory activities against α-glucosidase (EC 3.2.1.20), we employed ß-caryophyllene and some natural moieties (4-hydroxycoumarins, lawsone or syncarpic acid) to synthesize new types of meroterpene-like skeletons. All the products (including side products) were isolated and characterized by NMR, HR-MS, and ECD. RESULTS: In total, 17 products (representing seven scaffolds) were generated through a one-pot procedure. Most products (12 compounds) showed more potential activity (IC50 < 25 µM) than the positive controls (acarbose and genistein, IC50 58.19, and 54.74 µM, respectively). Compound 7 exhibited the most potent inhibition of α-glucosidase (IC50 3.56 µM) in a mixed-type manner. The CD analysis indicated that compound 7 could bind to α-glucosidase and influence the enzyme's secondary structure. CONCLUSIONS: Compound 7 could serve as a new type of template compound to develop α-glucosidase inhibitors. Full investigation of a biomimic reaction can be used as a concise strategy to explore diverse natural-like skeletons and search for novel lead compounds.


Assuntos
Materiais Biomiméticos/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Sesquiterpenos Policíclicos/farmacologia , Terpenos/farmacologia , Cinética , Espectroscopia de Ressonância Magnética , Terpenos/síntese química , Terpenos/química
19.
Drug Metab Rev ; 52(1): 19-43, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31984816

RESUMO

Today, it is very challenging to develop new active pharmaceutical ingredients. Developing good preparations of well-recognized natural medicines is certainly a practical and economic strategy. Low-solubility, low-permeability natural medicines (LLNMs) possess valuable advantages such as effectiveness, relative low cost and low toxicity, which is shown by the presence of popular products on the market. Understanding the in vivo metabolic and pharmacokinetic characteristics of LLNMs contributes to overcoming their associated problems, such as low absorption and low bioavailability. In this review, the structure-based metabolic reactions of LLNMs and related enzymatic systems, cellular and bodily pharmacological effects and metabolic influences, drug-drug interactions involved in metabolism and microenvironmental changes, and pharmacokinetics and dose-dependent/linear pharmacokinetic models are comprehensively evaluated. This review suggests that better pharmacological activity and pharmacokinetic behaviors may be achieved by modifying the metabolism through using nanotechnology and nanosystem in combination with the suitable administration route and dosage. It is noteworthy that novel nanosystems, such as triggered-release liposomes, nucleic acid polymer nanosystems and PEGylated dendrimers, in addition to prodrug and intestinal penetration enhancer, demonstrate encouraging performance. Insights into the metabolic and pharmacokinetic characteristics of LLNMs may help pharmacists to identify new LLNM formulations with high bioavailability and amazing efficacy and help physicians carry out LLNM-based precision medicine and individualized therapies.


Assuntos
Produtos Biológicos/farmacocinética , Animais , Produtos Biológicos/química , Flavonoides/química , Flavonoides/farmacocinética , Humanos , Permeabilidade , Solubilidade , Relação Estrutura-Atividade , Terpenos/química , Terpenos/farmacocinética
20.
Nat Commun ; 11(1): 508, 2020 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-31980637

RESUMO

The bicyclo[3.3.1]nonane architecture is a privileged structural motif found in over 1000 natural products with relevance to neurodegenerative disease, bacterial and parasitic infection, and cancer among others. Despite disparate biosynthetic machinery, alkaloid, terpene, and polyketide-producing organisms have all evolved pathways to incorporate this carbocyclic ring system. Natural products of mixed polyketide/terpenoid origins (meroterpenes) are a particularly rich and important source of biologically active bicyclo[3.3.1]nonane-containing molecules. Herein we detail a fully synthetic strategy toward this broad family of targets based on an abiotic annulation/rearrangement strategy resulting in a 10-step total synthesis of garsubellin A, an enhancer of choline acetyltransferase and member of the large family of polycyclic polyprenylated acylphloroglucinols. This work solidifies a strategy for making multiple, diverse meroterpene chemotypes in a programmable assembly process involving a minimal number of chemical transformations.


Assuntos
Vias Biossintéticas , Monoterpenos/metabolismo , Monoterpenos/síntese química , Monoterpenos/química , Oxirredução , Estereoisomerismo , Terpenos/síntese química , Terpenos/química
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