Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 124
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Bioorg Chem ; 93: 103321, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31585261

RESUMO

Bioassay-guided fractionation of the organic extract obtained from stem barks of the African plant Lophira lanceolata has led to the isolation of seven biflavonoids, including the new α'-chlorolophirone E (5) and 5'-chlorolophirone D (6). Among the isolated compounds, the bichalcone lophirone E was identified as a potent gametocytocidal agent with an IC50 value in the nanomolar range and negligible cytotoxicity (selectivity index = 570). Lophirone E proved to be about 100 times more active against P. falciparum stage V gametocytes than on asexual blood stages, thus exhibiting a unique stage-specific activity profile. The isolation of structural analogues allowed to draw preliminary structure-activity relationships, identifying the critical positions on the chemical scaffold of lophirone E.

2.
Fitoterapia ; 138: 104312, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31419464

RESUMO

The Alpine wormwood Artemisia vallesiaca All. was considered the most valuable ingredient of vermouth, a celebrated aromatized wine. A. vallesiaca has a very limited geographical distribution, and the booming market of vermouth decimated its natural population, resulting in the eventual replacement of this rare species with more common and less expensive wormwoods like A. absinthium L.. Over the past years, attempts to revive the original recipe(s) of vermouth have fostered the establishment of cultivations of A. vallesiaca in pre-montane settings. In order to assist these projects, the phytochemical profile of cultivated plants and of several native populations of A. vallesiaca from the Swiss Valais were comparatively evaluated, focusing on sesquiterpene lactones and on lipophilic flavonoids, the hallmark constituents of Artemisia species. Remarkably, no significant difference was detected between the samples, despite the different origins. The lipophilic flavonoids of A. vallesiaca were similar to those of related species used in the production of vermouth, but the presence of C-9 oxygenated 11ß-methyl germacranolides and eudesmanolides (herbolides) made its sesquiterpene lactone profile peculiar. In addition to known compounds, two novel germacranolides were also characterized (herbolides J and K), and the major sesquiterpene lactone from the plant, the bitter germacranolide herbolide D (4), was detected and quantified by 1H NMR in a bitter liqueur aromatized with A. vallesiaca. Taken together, these observations qualify herbolides as marker to identify A. vallesiaca in aromatized alcohol matrixes.


Assuntos
Artemisia/química , Lactonas/química , Sesquiterpenos de Germacrano/química , Vinho , Itália , Compostos Fitoquímicos/química
3.
Org Lett ; 21(15): 6122-6125, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31339327

RESUMO

The thermal degradation of cannabichromene (CBC, 3) is dominated by cationic reactions and not by the pericyclic rearrangements observed in model compounds. The rationalization of these differences inspired the development of a process that coupled, in an aromatization-driven single operational step, the condensation of citral and alkylresorciniols to homoprenylchromenes and their in situ deconstructive annulation to benzo[c]chromenes. This process was applied to a total synthesis of cannabinol (CBN, 5) and to its molecular editing.

4.
Fitoterapia ; 137: 104188, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31158428

RESUMO

Repeated chromatographic purifications of aerial parts of the Tunisian plant Daucus virgatus led to the isolation of four new germacranolides, named daucovirgolides I-L (2-5), along with the Plasmodium transmission-blocking agent daucovirgolide G. The chemical structures of the new compounds were defined as mono- or di-angeloylated germacrane-type sesquiterpenoids by spectroscopic (mainly 1D and 2D NMR) and spectrometric methods (ESIMS). The low potency exhibited by daucovirgolides I-L further supports the observation that strict structural requirements do exist for the Plasmodium transmission blocking activity in the daucovirgolide series. In particular, the endocyclic double bond system seems to be crucial for bioactivity.


Assuntos
Antimaláricos/farmacologia , Apiaceae/química , Plasmodium berghei/efeitos dos fármacos , Sesquiterpenos de Germacrano/farmacologia , Antimaláricos/isolamento & purificação , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Componentes Aéreos da Planta/química , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Germacrano/isolamento & purificação , Tunísia
5.
Planta Med ; 85(11-12): 981-986, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30934093

RESUMO

A general protocol for the selective mono-O-methylation of resorcinyl phytocannabinoids was developed. The availability of semisynthetic monomethyl analogues of cannabigerol, cannabidiol, and cannabidivarin (1A: -3A: , respectively) made it possible to quantify these minor phytocannabinoids in about 40 different chemotypes of fiber hemp. No chemotype significantly accumulated mono-O-methyl cannabidiol (2B: ) or its lower homologue (3B: ), while at least three chemotypes containing consistent amounts (≥ 400 mg/kg) of O-methylcannabigerol (1B: ) were identified. O-Methylation of alkyl phytocannabinoids (1B: -3B: ) does not significantly change the activity on peroxisome proliferator-activated receptors in contrast to what was reported for phenethyl analogues.


Assuntos
Canabinoides/química , Cannabis/química , Flores/química , Canabinoides/síntese química , Canabinoides/metabolismo , Canabinoides/farmacologia , Cannabis/metabolismo , Flores/metabolismo , Células HEK293 , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Receptores Ativados por Proliferador de Peroxissomo/efeitos dos fármacos
6.
J Agric Food Chem ; 67(11): 3159-3167, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30807134

RESUMO

Bergamot ( Citrus bergamia) is cultivated in Southern Italy almost exclusively to produce the prized essential oil, a top note in several perfumes. The juice of bergamot, until recently poorly studied, is the object of a growing scientific interest due to its claimed activity to treat metabolic syndrome. The aim of this investigation was a detailed characterization of bergamot juice polyphenolic fraction (BPF) based on a UPLC-DAD-MS analysis complemented by preparative chromatographic separations, followed by NMR characterization of the isolated compounds. The combination of these techniques efficiently covered different classes of secondary metabolites, leading to the identification of 39 components, several of which had never been reported from bergamot. One of them, bergamjuicin (35), is a new flavanone glycoside, whose structure has been determined by MS and NMR techniques. The reported results could provide a guide for future routine analyses of BPF, a material of great nutraceutical and industrial interest.


Assuntos
Citrus/química , Compostos Fitoquímicos/química , Extratos Vegetais/química , Polifenóis/química , Cromatografia Líquida de Alta Pressão , Frutas/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas
7.
Malar J ; 18(1): 35, 2019 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-30736813

RESUMO

BACKGROUND: Medicinal plant research may contribute to develop new pharmacological control tools for vector borne diseases, such as malaria. METHODS: The effects of methanol extracts (ME) obtained from seed kernel of ripe and unripe Azadirachta indica fruits were studied on erythrocytic proliferation of the rodent malaria parasite Plasmodium berghei strain ANKA and on mice pro-inflammatory response, as evaluated by measuring the matrix-metalloproteinase-9 (MMP-9) and tumour necrosis factor (TNF) plasma levels, in two mouse strains (C57BL/6 and BALB/c) which are considered as prototypical of Th1 and Th2 immune response, respectively. RESULTS: ME obtained from seed kernel of unripe Azadirachta indica fruits decreased by about 30% the proportion of erythrocytes infected with the malaria parasite in C57BL/6 mice in the 4 days suppressive test. In this treatment group, MMP-9 and TNF levels were notably higher than those measured in the same mouse strain treated with the anti-malarial drug artesunate, Azadirachta indica kernel extracts from ripe fruits or solvent. In BALB/c mice, treatment with kernel extracts did not influence parasitaemia. MMP-9 and TNF levels measured in this mouse strain were notably lower than those recorded in C57BL/6 mice and did not vary among treatment groups. CONCLUSIONS: The effects of the ME on the parasite-host interactions appeared to be mouse strain-dependent, but also related to the ripening stage of the neem fruits, as only the unripe fruit seed kernel extracts displayed appreciable bioactivity.


Assuntos
Antimaláricos/farmacologia , Azadirachta/química , Malária/tratamento farmacológico , Parasitemia/tratamento farmacológico , Extratos Vegetais/farmacologia , Plasmodium berghei/efeitos dos fármacos , Animais , Sistemas de Liberação de Medicamentos , Eritrócitos/parasitologia , Feminino , Inflamação/tratamento farmacológico , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Plantas Medicinais/química , Sementes/química
8.
Fitoterapia ; 134: 129-134, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30794919

RESUMO

Anvillea garcinii is a medicinal plant used in the Arab region for intestinal diseases, lungs and liver diseases, digestive problems, and as an anti-diabetic. Repeated chromatographic purifications of A. garcinii leaves led to the isolation of two undescribed guaiane sesquiterpene lactones (1-2), along with four known germacranolides (3-6). The structures of the new compounds were established using spectroscopic (1D, 2D NMR) and spectrometric methods (ESIMS). Compounds 1 and 2 were shown to possess hydroxyl substituents at position 9, a structural feature rarely reported in guaianolide-type sesquiterpenes. The antimicrobial activity of 1-6 was screened against five different gram-positive/negative bacteria and the fungi Candida albicans and C. parapsilosis. Compounds 1 and 2 displayed remarkable antifungal effect against C. albicans and C. parapsilosis and potent antibacterial activities against Staphylococcus aureus.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Asteraceae/química , Sesquiterpenos de Guaiano/farmacologia , Antibacterianos/isolamento & purificação , Antifúngicos/isolamento & purificação , Testes de Sensibilidade Microbiana , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Folhas de Planta/química , Plantas Medicinais/química , Arábia Saudita , Sesquiterpenos de Guaiano/isolamento & purificação
9.
Biochemistry ; 57(44): 6367-6378, 2018 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-30298725

RESUMO

Ebola virus (EBOV) is a filovirus that causes a severe and rapidly progressing hemorrhagic syndrome; a recent epidemic illustrated the urgent need for novel therapeutic agents because no drugs have been approved for treatment of Ebola virus. A key contribution to the high lethality observed during EBOV outbreaks comes from viral evasion of the host antiviral innate immune response in which viral protein VP35 plays a crucial role, blocking interferon type I production, first by masking the viral double-stranded RNA (dsRNA) and preventing its detection by the pattern recognition receptor RIG-I. Aiming to identify inhibitors of the interaction of VP35 with the viral dsRNA, counteracting the VP35 viral innate immune evasion, we established a new methodology for high-yield recombinant VP35 (rVP35) expression and purification and a novel and robust fluorescence-based rVP35-RNA interaction assay ( Z' factor of 0.69). Taking advantage of such newly established methods, we screened a small library of Sardinian natural extracts, identifying Limonium morisianum as the most potent inhibitor extract. A bioguided fractionation led to the identification of myricetin as the component that can inhibit rVP35-dsRNA interaction with an IC50 value of 2.7 µM. Molecular docking studies showed that myricetin interacts with the highly conserved region of the VP35 RNA binding domain, laying the basis for further structural optimization of potent inhibitors of VP35-dsRNA interaction.

10.
Nutrients ; 10(9)2018 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-30223482

RESUMO

Doxorubicin is a highly active antineoplastic agent, but its clinical use is limited because of its cardiotoxicity. Although nutraceuticals endowed with anti-inflammatory properties exert cardioprotective activity, their bioavailability and stability are inconsistent. In an attempt to address this issue, we evaluated whether bioavailable nanoemulsions loaded with nutraceuticals (curcumin and fresh and dry tomato extracts rich in lycopene) protect cardiomyoblasts (H9C2 cells) from doxorubicin-induced toxicity. Nanoemulsions were produced with a high-pressure homogenizer. H9C2 cells were incubated with nanoemulsions loaded with different nutraceuticals alone or in combination with doxorubicin. Cell viability was evaluated with a modified MTT method. The levels of the lipid peroxidation products malondialdehyde (MDA) and 4-hydroxy-2-butanone (4-HNA), and of the cardiotoxic-related interleukins IL-6, IL-8, IL-1ß and IL-10, tumor necrosis factor-alpha (TNF-α), and nitric oxide were analyzed in cardiomyoblasts. The hydrodynamic size of nanoemulsions was around 100 nm. Cell viability enhancement was 35⁻40% higher in cardiomyoblasts treated with nanoemulsion + doxorubicin than in cardiomyoblasts treated with doxorubicin alone. Nanoemulsions also protected against oxidative stress as witnessed by a reduction of MDA and 4-HNA. Notably, nanoemulsions inhibited the release of IL-6, IL-8, IL-1ß, TNF-α and nitric oxide by around 35⁻40% and increased IL-10 production by 25⁻27% versus cells not treated with emulsions. Of the nutraceuticals evaluated, lycopene-rich nanoemulsions had the best cardioprotective profile. In conclusion, nanoemulsions loaded with the nutraceuticals described herein protect against cardiotoxicity, by reducing inflammation and lipid oxidative stress. These results set the stage for studies in preclinical models.

11.
Nat Prod Rep ; 2018 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-30246844

RESUMO

Covering: up to 2018Even today, when planar structures of natural products can be determined with microgram samples, the configurational assignment continues to be a challenge. The relative and absolute configurations of natural products can be assigned by devising original approaches, relying on carefully acquired data on a case-by-case basis. In this review, the most widely available methods and techniques for the absolute configuration determination of novel natural products are concisely discussed. Selected illustrative examples (case studies) are presented, where original approaches integrating different chemical, spectroscopic, and/or computational methods have been devised to solve intriguing stereochemistry issues of natural small molecules.

12.
Bioorg Med Chem ; 26(15): 4532-4536, 2018 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-30077611

RESUMO

Electrophilic attack to a double bond, the classic trigger of intramolecular isoprenoid cyclizations, is apparently silent in Cannabis and the diversity of the cannabinome can be ultimately traced to the oxidative cyclization of cannabigerolic acid (CBGA, 1a), a process triggered by the generation of an aromatic electrophilic species. To expand the chemical space of the cannabinoid chemotype, we have investigated an oxidative trigger based on the addition of iodine to the terminal isoprenyl double bond of cannabigerol (CBG, 1b), the decarboxylated and thermally stable version of CBGA (1a). Apart from the predictable product of an iodine-induced cascade cyclization (3), also a pair of unprecedented spiranes named spirocannabigerols (4a,b), derived from the formation of an edge-protonated cyclopropyl cation was also formed, along with a product (5) resulting from the incorporation, in a Friedel-Craft fashion, of the reaction solvent (toluene). Biological evaluation of these compounds on six thermo-transient receptor potential channels (TRPs) showed a remodeling of bioactivity compared to GBC, with emphasis on TRPA1 rather than TRPM8.

13.
Molecules ; 23(7)2018 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-30018233

RESUMO

Phytochemical investigation of the apolar extract obtained from aerial parts of the Iranian endemic plant Echinophora platyloba DC (Apiaceae) resulted in the characterization of the polyacetylene fraction of this plant. This resulted to be composed of the known echinophorins A and B, embedding the very rare α-pyrone terminal, and of the new echinophorin D (3), including also three conjugated triple bonds. The chemical structures of these compounds were secured by detailed inspection of MS and 1D/2D NMR spectra. The isolated polyacteylenes were evaluated for their modulation of six thermo-TRP channels and they revealed a selective activity on TRPA1, an ion channel involved in the mediation of neuropathic and inflammatory pain. This is the first report on the activity of plant polyacetylenes on transient receptor potential (TRP) channels.


Assuntos
Apiaceae/química , Poli-Inos/química , Poli-Inos/farmacologia , Canal de Cátion TRPA1/antagonistas & inibidores , Células HEK293 , Humanos , Irã (Geográfico) , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Canal de Cátion TRPA1/metabolismo
15.
Nat Prod Res ; : 1-6, 2018 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-29397771

RESUMO

During our search for potential templates of HIV-1 reverse transcriptase (RT) and integrase (IN) dual inhibitors, the methanolic extract obtained from aerial parts of Limonium morisianum was investigated. Repeated bioassay-guided chromatographic purifications led to the isolation of the following secondary metabolites: myricetin, myricetin 3-O-rutinoside, myricetin-3-O-(6″-O-galloyl)-ß-d-galactopyranoside, (-)-epigallocatechin 3-O-gallate, tryptamine, ferulic and phloretic acids. The isolated compounds were tested on both HIV-1 RT-associated RNase H and IN activities. Interestingly, (-)-epigallocatechin-3-O-gallate and myricetin-3-O-(6″-O-galloyl)-ß-d-galactopyranoside potently inhibited both enzyme activities with IC50 values ranging from 0.21 to 10.9 µM. Differently, tryptamine and ferulic acid exhibited a significant inhibition only on the IN strand transfer reaction, showing a selectivity for this viral enzyme. Taken together these results strongly support the potential of this plant as a valuable anti HIV-1 drugs source worthy of further investigations.

16.
Fitoterapia ; 125: 13-17, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29242038

RESUMO

Vitis vinifera cv Falanghina is an ancient grape variety of Southern Italy. A thorough phytochemical analysis of the Falanghina leaves was conducted to investigate its specialised metabolite content. Along with already known molecules, such as caftaric acid, quercetin-3-O-ß-d-glucopyranoside, quercetin-3-O-ß-d-glucuronide, kaempferol-3-O-ß-d-glucopyranoside and kaempferol-3-O-ß-d-glucuronide, a previously undescribed biflavonoid was identified. For this last compound, a moderate bioactivity against metastatic melanoma cells proliferation was discovered. This datum can be of some interest to researchers studying human melanoma. The high content in antioxidant glycosylated flavonoids supports the exploitation of grape vine leaves as an inexpensive source of natural products for the food industry and for both pharmaceutical and nutraceutical companies. Additionally, this study offers important insights into the plant physiology, thus prompting possible technological researches of genetic selection based on the vine adaptation to specific pedo-climatic environments.


Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Biflavonoides/isolamento & purificação , Folhas de Planta/química , Vitis/química , Antineoplásicos Fitogênicos/farmacologia , Biflavonoides/farmacologia , Linhagem Celular Tumoral , Humanos , Itália , Melanoma , Estrutura Molecular , Compostos Fitoquímicos/análise
17.
J Nat Prod ; 81(3): 630-633, 2018 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-29240420

RESUMO

Treatment with iodine cleanly converts various p-menthane-type phytocannabinoids and their carboxylated precursors into cannabinol (CBN, 1a). The reaction is superior to previously reported protocols in terms of simplicity and substrate range, which includes not only tricyclic tetrahydrocannabinols such as Δ9-THC (2a) but also bicyclic phytocannabinoids such as cannabidiol (CBD, 3a). Lower homologues from the viridin series (2c and 3c, respectively) afforded cannabivarin (CBV), a non-narcotic compound that, when investigated against a series of ionotropic (thermo-TRPs) biological end-points of phytocannabinoids, retained the submicromolar TRPA1-activating and TRPM8-inhibiting properties of CBN, while also potently activating TRPV2. Treatment with iodine provides an easy access to CBN (1a) from crude extracts and side-cuts of the purification of Δ9-THC and CBD from respectively narcotic Cannabis sativa (marijuana) and fiber hemp, substantially expanding the availability of this compound and, in the case of fiber hemp, dissecting it from narcotic phytocannabinoids.

18.
J Nat Prod ; 80(10): 2787-2794, 2017 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-28976194

RESUMO

Phytochemical investigation of the aerial parts of the Tunisian plant Daucus virgatus led to the isolation of eight new germacranolides named daucovirgolides A-H (1-8). The stereostructures of these sesquiterpene lactones, decorated by either one or two angeloyl groups, have been determined by a combination of MS, NMR spectroscopy, chemical derivatization, and comparison of experimental electronic circular dichroism curves with TDDFT-predicted data. Daucovirgolide G (7) proved to be the single member of this family to possess a marked inhibitory activity (92% at 50 µg/mL) on the development of Plasmodium early sporogonic stages, the nonpathogenic transmissible stages of malaria parasites, devoid of general cytotoxicity. The selective activity of daucovirgolide G points to the existence of strict structural requirements for this transmission-blocking activity and therefore of a well-defined, although yet unidentified, biological target.


Assuntos
Antimaláricos/isolamento & purificação , Antimaláricos/farmacologia , Apiaceae/química , Componentes Aéreos da Planta/química , Sesquiterpenos de Germacrano/isolamento & purificação , Sesquiterpenos de Germacrano/farmacologia , Antimaláricos/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Plasmodium/efeitos dos fármacos , Sesquiterpenos de Germacrano/química , Tunísia
19.
Phytochemistry ; 144: 52-57, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28888145

RESUMO

Lycium barbarum (Solanaceae), long known to the traditional Chinese medicine because of its many health-promoting effects, has of late spread widely across the Western hemisphere, mainly on account of the nutritional richness in vitamins, minerals and antioxidant metabolites of its fruits. Data on bioactive metabolites from fruits and leaves, which are commonly consumed in soups and salads, are scarce and sometimes even contradictory. By means of NMR, the present study identified the specialised products contained in an Italian cultivar of L. barbarum. Kaempeferol, caffeic acid, 3,4,5-trihydroxycinnamic acid and 5-hydroxyferulic acid were found in fresh fruits; rutin and chlorogenic acid were detected in leaves and flowers; also, a previously undescribed N,N-dicaffeoylspermidine derivative was identified in flowers, while N-feruloyltyramine derivatives, for which interesting anti-inflammatory properties have been reported, turned out to be the major bioactive molecules in stems. The plethora of the detected bioactive molecules amplifies the nutraceutical value of berries and leaves and prompts the exploitation of L. barbarum flowers and pruned stems as sources of beneficial compounds.


Assuntos
Ácidos Cafeicos/análise , Ácido Clorogênico/análise , Ácidos Cumáricos/análise , Inibidores Enzimáticos/análise , Lycium/química , Rutina/análise , Tiramina/análogos & derivados , Araquidonato 5-Lipoxigenase/metabolismo , Ácidos Cafeicos/metabolismo , Ácidos Cafeicos/farmacologia , Linhagem Celular Tumoral , Ácido Clorogênico/metabolismo , Ácido Clorogênico/farmacologia , Ácidos Cumáricos/metabolismo , Ácidos Cumáricos/farmacologia , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/farmacologia , Flores/química , Frutas/química , Humanos , Itália , Espectroscopia de Ressonância Magnética , Medicina Tradicional Chinesa , Folhas de Planta/química , Rutina/metabolismo , Rutina/farmacologia , Tiramina/análise , Tiramina/metabolismo , Tiramina/farmacologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA