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1.
Nat Commun ; 11(1): 4372, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873801

RESUMO

3D molecular structure determination is a challenge for organic compounds or natural products available in minute amounts. Proton/proton and proton/carbon correlations yield the constitution. J couplings and NOEs oftentimes supported by one-bond 1H,13C residual dipolar couplings (RDCs) or by 13C residual chemical shift anisotropies (RCSAs) provide the relative configuration. However, these RDCs or carbon RCSAs rely on 1% natural abundance of 13C preventing their use for compounds available only in quantities of a few 10's of µgs. By contrast, 1H RCSAs provide similar information on spatial orientation of structural moieties within a molecule, while using the abundant 1H spin. Herein, 1H RCSAs are accurately measured using constrained aligning gels or liquid crystals and applied to the 3D structural determination of molecules with varying complexities. Even more, deuterated alignment media allow the elucidation of the relative configuration of around 35 µg of a briarane compound isolated from Briareum asbestinum.


Assuntos
Antozoários/química , Produtos Biológicos/química , Diterpenos/química , Conformação Molecular , Prótons , Animais , Anisotropia , Espectroscopia de Prótons por Ressonância Magnética
2.
Food Chem ; 331: 127292, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-32559599

RESUMO

Food supplementation with vitamin A is an efficient strategy to combat vitamin A deficiency. The stability of vitamin A during cooking and storage is, however, low. We here show that cereal bran protects retinyl palmitate (RP) during simmering and storage. Native wheat bran stabilized RP the most during simmering. About 75% RP was recovered after 120 min of cooking, while all RP was lost after 80 min in the absence of bran. Heat-treated rice bran protected RP the best during forced storage, with a 35% recovery after 8 weeks. RP was degraded entirely in the absence of bran in less than one week. Results suggested that the physical entrapment of oil within the large wheat bran particles protects RP from the action of water and pro-oxidants during simmering. During storage, the high amount and diversity of lipid components present in rice bran are presumably responsible for its protective effect.


Assuntos
Culinária , Fibras na Dieta/análise , Armazenamento de Medicamentos , Grão Comestível/química , Vitamina A/química , Diterpenos/química , Espécies Reativas de Oxigênio/química , Vitamina A/análogos & derivados , Água/química
3.
Food Chem ; 329: 127129, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32497844

RESUMO

The acknowledged marker of Robusta coffee, 16-O-methylcafestol (16-OMC), can be quantified by NMR as a mixture with 16-O-methylkahweol (16-OMK), which accounts for approximately 10% of the mixture. In the present study, we detected and quantified 16-O-methylated diterpenes (16-OMD) in 248 samples of green Coffea arabica beans by NMR. We did not observe any differences between genotypes introgressed by chromosomal fragments of Robusta and non-introgressed genotypes. Environmental effects suggesting a possible protective role of 16-OMD for adaptation, as well as genotypic effects that support a high heritability of this trait were observed. Altogether, our data confirmed the presence of 16-OMD in green Arabica at a level approximately 1.5% that of a typical Robusta, endorsing the validity of 16-OMD as a marker for the presence of Robusta.


Assuntos
Coffea/genética , Diterpenos/química , Coffea/química , Café/química , Café/genética , Cor , Genótipo , Espectroscopia de Ressonância Magnética , Metilação , Estrutura Molecular , Sementes/química , Sementes/genética
4.
Proc Natl Acad Sci U S A ; 117(20): 10688-10698, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32371485

RESUMO

AIDS is a pandemic disease caused by HIV that affects 37 million people worldwide. Current antiretroviral therapy slows disease progression but does not eliminate latently infected cells, which resupply active virus, thus necessitating lifelong treatment with associated compliance, cost, and chemoexposure issues. Latency-reversing agents (LRAs) activate these cells, allowing for their potential clearance, thus presenting a strategy to eradicate the infection. Protein kinase C (PKC) modulators-including prostratin, ingenol esters, bryostatin, and their analogs-are potent LRAs in various stages of development for several clinical indications. While LRAs are promising, a major challenge associated with their clinical use is sustaining therapeutically meaningful levels of the active agent while minimizing side effects. Here we describe a strategy to address this problem based on LRA prodrugs, designed for controllable release of the active LRA after a single injection. As intended, these prodrugs exhibit comparable or superior in vitro activity relative to the parent compounds. Selected compounds induced higher in vivo expression of CD69, an activation biomarker, and, by releasing free agent over time, significantly improved tolerability when compared to the parent LRAs. More generally, selected prodrugs of PKC modulators avoid the bolus toxicities of the parent drug and exhibit greater efficacy and expanded tolerability, thereby addressing a longstanding objective for many clinical applications.


Assuntos
Fármacos Anti-HIV/farmacologia , Briostatinas/farmacologia , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Pró-Fármacos/farmacologia , Proteína Quinase C/metabolismo , Latência Viral/efeitos dos fármacos , Animais , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/uso terapêutico , Briostatinas/síntese química , Briostatinas/uso terapêutico , Linhagem Celular Tumoral , Células Cultivadas , Diterpenos/química , Infecções por HIV/tratamento farmacológico , HIV-1/fisiologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Ésteres de Forbol/química , Pró-Fármacos/síntese química , Pró-Fármacos/uso terapêutico , Proteína Quinase C/efeitos dos fármacos
5.
Nat Commun ; 11(1): 1830, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32286350

RESUMO

A synthetic biology method based on heterologous biosynthesis coupled with genome mining is a promising approach for increasing the opportunities to rationally access natural product with novel structures and biological activities through total biosynthesis and combinatorial biosynthesis. Here, we demonstrate the advantage of the synthetic biology method to explore biological activity-related chemical space through the comprehensive heterologous biosynthesis of fungal decalin-containing diterpenoid pyrones (DDPs). Genome mining reveals putative DDP biosynthetic gene clusters distributed in five fungal genera. In addition, we design extended DDP pathways by combinatorial biosynthesis. In total, ten DDP pathways, including five native pathways, four extended pathways and one shunt pathway, are heterologously reconstituted in a genetically tractable heterologous host, Aspergillus oryzae, resulting in the production of 22 DDPs, including 15 new analogues. We also demonstrate the advantage of expanding the diversity of DDPs to probe various bioactive molecules through a wide range of biological evaluations.


Assuntos
Diterpenos/farmacologia , Fungos/química , Naftalenos/farmacologia , Pironas/farmacologia , Biologia Sintética , Peptídeos beta-Amiloides/metabolismo , Animais , Fármacos Anti-HIV/farmacologia , Aspergillus/química , Vias Biossintéticas/efeitos dos fármacos , Vias Biossintéticas/genética , Proliferação de Células/efeitos dos fármacos , Diterpenos/química , Drosophila/efeitos dos fármacos , Fungos/genética , Genoma Fúngico , HIV-1/efeitos dos fármacos , Humanos , Células MCF-7 , Naftalenos/química , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Agregados Proteicos , Pironas/química , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/metabolismo , Esferoides Celulares/patologia , Estereoisomerismo
6.
Mar Drugs ; 18(4)2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32331404

RESUMO

Further chemical investigation of the EtOAc extract of the soft coral Lobophytum varium resulted in the discovery of eleven new diterpenoids lobovarols F-P (1-11) of lobane- and prenyleudesmane-types, along with two known metabolites (12 and 13). The structures of the new metabolites were established by spectroscopic analyses, including 2D NMR experiments. The absolute configuration of 1 was determined using Mosher's method. The complete assignment of 1H and 13C NMR spectroscopic data of 12 and 13 and the identification of pyran-derived moieties in the prenyleudesmanes were reported for the first time. Anti-inflammatory activities of the isolated compounds in suppressing elastase release and superoxide anion generation in human neutrophils were disclosed for 1, 2, 4, 12, and 13. A stereospecific biosynthesis for lobanes and prenyleudesmanes from the related prenylgermacranes could explain the coexistence of lobanes and prenylgermacranes in L. varium.


Assuntos
Antozoários/química , Anti-Inflamatórios/isolamento & purificação , Diterpenos/isolamento & purificação , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Diterpenos/química , Diterpenos/farmacologia , Humanos , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Elastase Pancreática/metabolismo , Estereoisomerismo , Superóxidos/metabolismo
7.
Bol. latinoam. Caribe plantas med. aromát ; 19(2): 236-246, mar. 2020. ilus, tab
Artigo em Inglês | LILACS | ID: biblio-1104216

RESUMO

Chloroform extract (CE) and fractions obtained from Aldama arenaria roots were evaluated for their in vitro antiproliferative activity against 10 human tumor cell lines [leukemia (K-562), breast (MCF-7), ovary expressing a multidrug-resistant phenotype (NCI/ADR-RES), melanoma (UACC-62), lung (NCI-H460), prostate (PC-3), colon (HT29), ovary (OVCAR-3), glioma (U251), and kidney (786-0)]. CE presented weak to moderate antiproliferative activity (mean log GI50 1.07), whereas fractions 3 and 4, enriched with pimaranetype diterpenes [ent-pimara-8(14),15-dien-19-oic acid and ent-8(14),15-pimaradien-3ß-ol], presented moderate to potent activity for most cell lines, with mean log GI50 of 0.62 and 0.59, respectively. The results showed promising in vitro antiproliferative action of the samples obtained from A. arenaria, with the best results for NCI/ADR-RES, HT29, and OVCAR-3, and TGI values ranging from 5.95 to 28.71 µg.ml -1, demonstrating that compounds of this class may be potential prototypes for the discovery of new therapeutic agents.


El extracto de cloroformo (CE) y las fracciones obtenidas de las raíces de Aldama arenaria fueron evaluadas por su actividad antiproliferativa in vitro contra 10 líneas celulares tumorales humanas [leucemia (K-562), mama (MCF-7), ovario que expresa un fenotipo resistente a múltiples fármacos (NCI/ADR-RES), melanoma (UACC-62), pulmón (NCI-H460), próstata (PC-3), colon (HT29), ovario (OVCAR-3), glioma (U251) y riñón (786-0)]. CE presentó actividad antiproliferativa débil a moderada (log GI50 promedio de 1.07), mientras que las fracciones 3 y 4, enriquecidas con diterpenos de tipo pimarane [ent-pimara-8 (14), ácido 15-dien-19-oico y ent-8 (14), 15-pimaradien-3ß-ol], presentaron actividad moderada a potente para la mayoría de las líneas celulares, con un log GI50 promedio de 0.62 y 0.59, respectivamente. Los resultados mostraron una prometedora acción antiproliferativa in vitro de las muestras obtenidas de A. arenaria, con los mejores resultados para NCI/ADR-RES, HT29 y OVCAR-3, y valores de TGI que van desde 5.95 a 28.71 µg.ml -1, lo que demuestra que los compuestos de esta clase pueden ser prototipos potenciales para el descubrimiento de nuevos agentes terapéuticos.


Assuntos
Extratos Vegetais/farmacologia , Clorofórmio , Plectranthus/química , Linhagem Celular Tumoral/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Técnicas In Vitro , Extratos Vegetais/química , Etnobotânica , Cuba , Diterpenos/farmacologia , Diterpenos/química
8.
Yakugaku Zasshi ; 140(3): 355-362, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32115552

RESUMO

In our continuing search for secondary metabolites from plants, we investigated the chemical constituents of various Okinawan plants. From the stems and leaves of Croton cascarilloides (Euphorbiaceae), a great number of rare diterpenoids: crotofolanes; crotocascarins A-Q, and new diterpenoids; rearranged nor-crotofolanes: crotocascarins α-γ; a rearranged crotofolane: neocrotocascarin; and a new skeletal diterpenoid: isocrotofolane glucoside were isolated. Their structures were mainly elucidated from NMR spectroscopic evidence. In addition, absolute configurations of crotocascarins A, B, K and O, crotocascarin α and neocrotocascarin were determined by X-ray crystallographic analyses, chiral HPLC analyses of 2-methylbutyric acid in their molecules, application of the circular dichroism rule for the α,ß-unsaturated γ-lactone ring, and the modified Mosher's method. The absolute structures of crotofolanes were reported for the first time, and a biosynthetic mechanism for the formation of crotocascarin α and neocrotocascarin from crotocascarin B was proposed. Other interesting compounds, namely diosmarioside H: a dimeric ent-kaurane glycoside from the leaves of Diospyros maritima, and melionosides A-C: megastigmane glucosides with a spiro-ring structure from the leaves of Meliosma lepidota ssp. squamulata were also isolated.


Assuntos
Croton/química , Diterpenos/química , Diterpenos/isolamento & purificação , Japão , Espectroscopia de Ressonância Magnética , Solubilidade
9.
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
10.
Phytochemistry ; 171: 112234, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31901735

RESUMO

A total of fifteen grayanane diterpenoid glucosides including eight undescribed ones, pierisjaponosides A-H, were isolated from the leaves of Pieris japonica (Thunb.) D. Don ex G. Don (Ericaceae). Their structures were established by extensive spectros copic techniques including HRESIMS and NMR, as well as chemical methods. The absolute configurations of pierisjaponosides A, B, and D were finally established by single-crystal X-ray diffraction with Cu Kα radiation. This is the first time to report the crystal structure of a 5,9-epoxygrayanane diterpenoid glucoside. Pierisjaponoside E represents the first example of a 9ß-hydroxygrayan-1(10)-ene diterpenoid. All the isolated grayanane diterpenoid glucosides were evaluated for their analgesic activities in the acetic acid-induced writhing models in mice, and showed significant analgesic effects. Pierisjaponosides A and C-H, micranthanoside A, pieroside A, and craiobiosides A and B displayed significant analgesic effects with the writhe inhibition rates over 50% at a dose of 5.0 mg/kg. Pierisjaponoside E exhibited significant analgesic activities with the percentage inhibitions of 81.7%, 70.4%, and 52.1% at the doses of 5.0, 1.0, and 0.2 mg/kg, respectively. The preliminary structure-activity relationships of grayanane diterpenoid glucosides as potent analgesics were discussed, giving some clues to design novel analgesics.


Assuntos
Analgésicos/uso terapêutico , Diterpenos/uso terapêutico , Ericaceae/química , Glucosídeos/uso terapêutico , Dor/tratamento farmacológico , Compostos Fitoquímicos/uso terapêutico , Ácido Acético , Analgésicos/química , Analgésicos/isolamento & purificação , Animais , Diterpenos/química , Diterpenos/isolamento & purificação , Relação Dose-Resposta a Droga , Feminino , Glucosídeos/química , Glucosídeos/isolamento & purificação , Masculino , Camundongos , Camundongos Endogâmicos , Modelos Moleculares , Estrutura Molecular , Dor/induzido quimicamente , Medição da Dor , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Folhas de Planta/química , Relação Estrutura-Atividade
11.
Chem Pharm Bull (Tokyo) ; 68(1): 96-99, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31902905

RESUMO

Chemical investigation of the aerial parts of Andrographis paniculata resulted in isolation of nine compounds, including a new ent-labdane diterpenoid, andrographic acid methyl ester (1), a new chalcone glucoside, pashanone glucoside (5), and seven known metabolites, andrograpanin (2), andrographolide (3), andropanolide (4), andrographidine A (6), andrographidine F (7), 6-epi-8-O-acetyl-harpagide (8), and curvifloruside F (9). Their chemical structures were elucidated based on comprehensive analyses of the spectroscopic data, including NMR and MS. Among the isolated compounds, andropanolide exerted cytotoxicity toward LNCaP, HepG2, KB, MCF7, and SK-Mel2 carcinoma cells, with IC50 values ranging from 31.8 to 45.9 µM. In addition, andropanolide significantly inhibited the overproduction of nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, with an IC50 value of 13.4 µM.


Assuntos
Andrographis/química , Diterpenos/química , Flavonoides/química , Andrographis/metabolismo , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Humanos , Lipopolissacarídeos/toxicidade , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Espectroscopia de Ressonância Magnética , Camundongos , Conformação Molecular , Óxido Nítrico/metabolismo , Componentes Aéreos da Planta/química , Componentes Aéreos da Planta/metabolismo , Células RAW 264.7
12.
Med Sci Monit ; 26: e920248, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31935210

RESUMO

BACKGROUND Cervical cancer is a major threat to female health worldwide. This study was performed to study the anticancer potential of sclareol and as a chemo-sensitizing agent against human cervical cancer cells along with evaluating its effects on apoptosis, cell cycle arrest, and MAPK/ERK signaling pathway. MATERIAL AND METHODS MTT assay was performed to check cell viability, morphological changes were observed through phase-contrast microscopy, DAPI (4',6-diamidino-2-phenylindole) staining and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labelling) assays were performed to evaluate apoptotic effects; MMP (matrix metalloproteinase) and cell cycle analysis were examined through flow cytometry. Western blotting analysis was performed to check the protein expressions of MAPK/ERK signaling pathway and apoptosis proteins. RESULTS Results depicted that both sclareol and cisplatin induced cytotoxic effects individually but when used in combination, it led to much more pronounced cytotoxic effects indicating a synergistic effect of sclareol on cisplatin. Sclareol treatment led to significant decrease in the levels of p-MEK and p-ERK. Significant morphological changes (including chromatin condensation, nuclear fragmentation) in cervical cancer cells were seen after treatment. Western blot showed significant alterations including increase in BAX and decrease in BCL-2 levels. An increase in the S-phase cells, indicating cell cycle arrest at S-phase was seen along with modulating the expressions of CDK-1and Cdc25C, and increase in the levels of p-CDK-1, cyclin-B1, cyclin-A, and p-Cdc25C. CONCLUSIONS Sclareol not only induced cytotoxic effects but also enhanced chemosensitivity of human cervical cancer cells towards cisplatin and these effects are mediated via MAPK/ERK signaling pathway, stimulation of apoptosis and S-phase cell cycle arrest.


Assuntos
Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Diterpenos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Mitocôndrias/metabolismo , Fase S/efeitos dos fármacos , Neoplasias do Colo do Útero/enzimologia , Neoplasias do Colo do Útero/patologia , Proteínas de Ciclo Celular/metabolismo , Forma Celular/efeitos dos fármacos , Diterpenos/química , Feminino , Células HeLa , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos
13.
Mar Drugs ; 18(1)2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31947850

RESUMO

We performed a high-content screening (HCS) assay aiming to discover bioactive molecules with proteasome inhibitory activity. By structural elucidation, we identified six compounds purified from soft coral Clavularia flava, which potentiates proteasome inhibition. Chemical structure elucidation revealed they are dolabellane- and secosteroid-based compounds including a new dolabellane, clavinflol C (1), three known dolabellanes, stolonidiol (2), stolonidiol-17-acetate (3), and clavinflol B (4) as well as two new secosteroids, 3,11-dihydroxy-24-methyl-9,11-secocholest-5-en-9,23-dione (5) and 3,11-dihydroxy-24-methylene-9,11-secocholest-5-en-9,23-dione (6). All six compounds show less cytotoxicity than those of known proteasome inhibitors, bortezomib and MG132. In summary, the high-content measurements of control inhibitors, bortezomib and MG132, manifest the highest ratio >2 in high-content measurement. Of the isolated compounds, 2 and 5 showed higher activity, followed by 3 and 6, and then 1 and 4 exhibited moderate inhibition.


Assuntos
Antozoários/química , Diterpenos/química , Complexo de Endopeptidases do Proteassoma/química , Secoesteroides/química , Ubiquitina/química , Animais , Bortezomib/química , Inibidores de Proteassoma/química
14.
Phytochemistry ; 170: 112198, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31765875

RESUMO

Fungal endophytes from plants are an important source for discovery of novel bioactive natural products. In this study, five undescribed harziane diterpenoids with a 4/7/5/6 tetracyclic scaffold, harzianols F‒J and three known derivatives, were obtained from the liquid fermentation of an endophytic fungus Trichoderma atroviride B7, which was isolated from the healthy flower of a Lamiaceae plant Colquhounia coccinea var. mollis. Their structures were elucidated by comprehensive spectroscopic analyses and X-ray crystallographic diffraction in the case of harzianol F. Harzianol I exhibited significant antibacterial effect against the growth of Staphylococcus aureus (EC50 = 7.7 ± 0.8 µg/mL), Bacillus subtilis (EC50 = 7.7 ± 1.0 µg/mL), and Micrococcus luteus (EC50 = 9.9 ± 1.5 µg/mL). Meanwhile, cytotoxic activity of harzianol I against three cancer cell lines was also observed. A plausible biosynthetic pathway for harziane diterpenoids was proposed.


Assuntos
Antibacterianos/farmacologia , Diterpenos/farmacologia , Lamiaceae/química , Compostos Fitoquímicos/farmacologia , Trichoderma/química , Antibacterianos/química , Antibacterianos/isolamento & purificação , Bacillus subtilis/efeitos dos fármacos , Diterpenos/química , Diterpenos/isolamento & purificação , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Micrococcus luteus/efeitos dos fármacos , Conformação Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Staphylococcus aureus/efeitos dos fármacos
15.
Chem Biodivers ; 17(1): e1900600, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31793197

RESUMO

Four new hetisine-type C20 -diterpenoid alkaloids, named as coreanines A-D (1-4), were isolated from the roots of Aconitum coreanum, together with thirteen known alkaloids (5-17). Their structures were elucidated by extensive spectroscopic methods including IR, HR-ESI-MS and NMR techniques. All the isolated compounds were screened for the acetylcholinesterase (AChE) inhibitory effects, and none of them showed considerable inhibitory activity.


Assuntos
Acetilcolinesterase/metabolismo , Aconitum/química , Alcaloides/farmacologia , Inibidores da Colinesterase/farmacologia , Diterpenos/farmacologia , Raízes de Plantas/química , Alcaloides/química , Alcaloides/isolamento & purificação , Animais , Inibidores da Colinesterase/química , Inibidores da Colinesterase/isolamento & purificação , Diterpenos/química , Diterpenos/isolamento & purificação , Electrophorus , Estrutura Molecular
16.
J Chromatogr A ; 1612: 460621, 2020 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-31635786

RESUMO

Crocetane and phytane are two isoprenoids isomers with similar molecular structures and often present together in methane-seep sediments and some Palaeozoic crude oils. Their commonly co-elution on gas chromatography is challenging for quality and quantity analysis, making it impossible to determine their compound-specific isotopic composition, and thus, insight their geological and geochemical significance. A new gas chromatography method is reported here using a DB-17MS column (50%-phenyl-methyl polysiloxane as the stationary phase) that successfully achieved baseline separation of crocetane and phytane and can be used to accurately identify and quantify them on gas chromatography and gas chromatography-mass spectrometry. Routine steroids and terpenoids biomarkers can also be analysed simultaneously. Additionally, their compound-specific carbon isotopic compositions were also measured without matrix influence using this method. This is the first time that a simple chromatographic method for direct determination of compound-specific carbon isotopic composition of crocetane has been reported publicly.


Assuntos
Diterpenos/química , Cromatografia Gasosa-Espectrometria de Massas/métodos , Isótopos de Carbono/análise , Diterpenos/isolamento & purificação , Esteroides/análise , Terpenos/análise
17.
Fitoterapia ; 140: 104412, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31698060

RESUMO

Aconitum carmichaelii has been used in traditional Chinese medicine for treating various diseases for several thousand years. Based on the biosynthetic pathway of some alkaloids such as C19-diterpenoid alkaloids and obvious differences in alkaloid content between leaves of two A. carmichaelii varieties has been reported, we performed leaves transcriptome analysis of two A. carmichaelii varieties. Besides we characterized the biosynthetic pathway of salsolinol. A total of 56 million raw reads (8.28 G) and 55 million clean reads (8.24 G) were obtained from two varieties (Z175 and R184) leaves transcriptome, respectively, and 176,793 unigenes were annotated. 281 and 843 unigenes are involved in the salsolinol biosynthetic pathway and the formation of C19-diterpenoid alkaloids respectively. And including 34 and 24 unigenes are the differentially expressed genes (DEGs) in the biosynthesis pathway for C19-diterpenoid alkaloids and salsolinol between Z175 and R184 respectively, which were target genes to explore differences in C19-diterpenoid alkaloid and salsolinol biosynthesis in Z175 and R184. Thus genes involved in alkaloid biosynthesis and accumulation differ between varieties leaves. The mechanisms underlying the differences and their relevance require further exploration. The results expand our knowledge of alkaloids biosynthesis in A. carmichaelii leaves, and provide a theoretical basis for analysis differences in alkaloids biosynthesis patterns in different varieties.


Assuntos
Aconitum/química , Vias Biossintéticas , Isoquinolinas/química , Transcriptoma , Alcaloides/biossíntese , China , Diterpenos/química , Perfilação da Expressão Gênica , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Folhas de Planta/química , Plantas Medicinais/química
18.
Chem Biodivers ; 17(2): e1900531, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31825561

RESUMO

Euphorbia factor L3 , a lathyrane diterpenoid extracted from Euphorbia lathyris, was found to display good anti-inflammatory activity with very low cytotoxicity. To find more potent anti-inflammatory drugs, two series of Euphorbia factor L3 derivatives with fatty and aromatic acids were designed and synthesized. Among them, lathyrane derivative 5n exhibited most potent inhibition on LPS-induced NO production in RAW264.7 cells with no obvious cytotoxicity. To determine the key characteristics of Euphorbia factor L3 derivatives that contribute to anti-inflammatory activity, we conducted a structure-activity relationship study of these compounds.


Assuntos
Anti-Inflamatórios/síntese química , Diterpenos/química , Euphorbia/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Diterpenos/síntese química , Diterpenos/farmacologia , Euphorbia/metabolismo , Lipopolissacarídeos/toxicidade , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Células RAW 264.7 , Relação Estrutura-Atividade
19.
Phytochemistry ; 170: 112217, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31812109

RESUMO

Twelve ent-abietane and two ent-pimarane diterpenoids were isolated from the leaves of Croton mubango Müll. Arg. (Euphorbiaceae) collected in the Democratic Republic of the Congo. 2ß-Hydroxy-ent-abieta-7,13-dien-3-one, 15-hydroxy-ent-abieta-7,13-dien-3-one, 13α,15-dihydroxy-ent-abieta-8(14)-en-3-one, 2ß,9,13-trihydroxy-ent-abieta-7-en-3-one, 2ß,7ß-dihydroxy-ent-abieta-8,11,13-trien-3-one, 15-hydroxy-ent-abieta-8,11,13-trien-3-one and ent-pimara-8(14),15-dien-3-one and the ent-forms of the previously reported normal series diterpenoids, ent-abieta-8,11,13-trien-3-one, 7ß-hydroxy-ent-abieta-8,11,13-trien-3-one, 3α-hydroxy-ent-abieta-8,11,13-triene, 15-hydroxy-ent-abieta-8,11,13-triene and 6ß-hydroxy-ent-abieta-8,11,13-triene are reported here for the first time. Structures were established using HRESIMS, FTIR, NMR, DP4+ probability calculations and by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. Ent-pimara-8(14), 15-dien-3-one, showed antiproliferative activity against melanoma (MALME-3M), renal (UO-31) and ovarian cancer cell lines (IGROV1) at a concentration of 10-5 M in the NCI 60 screen.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Diterpenos/farmacologia , Euphorbiaceae/química , Compostos Fitoquímicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Diterpenos/química , Diterpenos/isolamento & purificação , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Conformação Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Relação Estrutura-Atividade
20.
Life Sci ; 241: 117164, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31838135

RESUMO

AIMS: This study was to assess whether andrographolide derivative (AL-1) could restore mucosal homeostasis and regulate tight junctions through MLCK-dependent pathway in DSS-induced colitis mice. MAIN METHODS: Colitis mice model was induced by daily administration of 2.5% DSS for seven days. The therapeutic effect was determined by evaluating the histopathological changes and the pro-inflammatory cytokine level. In addition, the effects of AL-1 on tight junctions were examined by immunohistochemistry and Western blot. The expressions of factors in MLCK-dependent pathway were evaluated by immunofluorescence and Western blot. KEY FINDINGS: AL-1 protected the intestinal barrier function in DSS-induced colitis mice. These protective effects were achieved by maintaining the normal mucus secretion and preserving tight junctions via suppression of the MLCK-dependent pathway. SIGNIFICANCE: AL-1 could prevent the increase in the DSS-induced intestinal permeability. These data indicated that AL-1 could be a promising agent for UC treatment.


Assuntos
Anti-Inflamatórios/farmacologia , Permeabilidade da Membrana Celular/fisiologia , Colite/tratamento farmacológico , Sulfato de Dextrana/toxicidade , Diterpenos/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Junções Íntimas/efeitos dos fármacos , Animais , Anti-Inflamatórios/química , Permeabilidade da Membrana Celular/efeitos dos fármacos , Colite/induzido quimicamente , Colite/metabolismo , Colite/patologia , Diterpenos/química , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Quinase de Cadeia Leve de Miosina/metabolismo , Fosforilação , Transdução de Sinais , Junções Íntimas/metabolismo , Junções Íntimas/patologia
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