Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.272
Filtrar
1.
J Pharm Biomed Anal ; 207: 114396, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34670180

RESUMO

Euphorbia pekinensis Rupr. (EP) (Euphorbiaceae), as Traditional Chinese Medicine (TCM), exhibits therapeutic effects on tumors in clinical practice. Anti-angiogenesis may be an underlying molecular mechanism of EP's actions. However, the anti-angiogenic active ingredients of EP remain unclear. The screening and analysis of anti-angiogenic agents were essential for the sufficient utilization and development of EP. Thus, we established a UPLC-QTOF-MS method based on a transgenic zebrafish model to screen anti-angiogenesis activity components in EP. UPLC-QTOF-MS was used to characterize compounds from EP and in vivo compounds in Tg (flk1: mCherry) zebrafish larvae treated with EP. Based on the identification results, five components were selected, and their anti-angiogenesis activity were investigated via assessment of intersegmental blood vessels during the development of the transgenic zebrafish. Three of these components (3,3'-O-dimethoxy ellagic acid, quercetin, and ingenol) are active components of EP with anti-angiogenic effects. Among them, 3, 3'-O-dimethoxy ellagic acid and ingenol were first demonstrated with anti-angiogenesis effects. UPLC-PDA analysis was performed on EP water extracts to determine anti-angiogenesis active ingredients quantitatively. In the concentration range of 100-200 µg/mL, EP and the active ingredient compositions, mixed according to the content of EP, had equivalent anti-angiogenesis activities. These experimental results indicate that the UPLC-QTOF-MS method, combined with a transgenic zebrafish model, is rapid, sensitive and reliable. The combination in TCM offers the potential to achieve certain effect levels with lower concentrations of the individual compound.


Assuntos
Medicamentos de Ervas Chinesas , Euphorbia , Inibidores da Angiogênese/farmacologia , Animais , Animais Geneticamente Modificados , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa , Peixe-Zebra
2.
Zhongguo Zhong Yao Za Zhi ; 46(17): 4433-4437, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34581047

RESUMO

The combination of normal-phase silica gel column chromatography, octadecyl silica(ODS) column chromatography, semi-preparative high performance liquid chromatography(HPLC), etc. was employed to isolate and purify the chemical components from Euphorbia resinifera, and 7 triterpenoids were separated from the ethanol extract of the medicinal materials. Their structures were identified by various spectroscopy methods as cycloartan-1,24-diene-3-one(1), cycloartan-1,24-diene-3-ol(2), 3ß-hydroxy-lanosta-8,24-diene-11-one(3), lnonotusane C(4), eupha-8,24-diene-3ß-ol-7,11-dione(5), eupha-24-methylene-8-ene-3ß-ol-7,11-dione(6), and eupha-8,24-diene-3ß,11ß-diol-7-one(7). Compounds 1 and 2 are new compounds, and compound 3 is obtained from nature for the first time.


Assuntos
Medicamentos de Ervas Chinesas , Euphorbia , Triterpenos , Estrutura Molecular
3.
Zhongguo Zhong Yao Za Zhi ; 46(18): 4744-4748, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34581084

RESUMO

Four new lanostane triterpenoids, 3ß-hydroxy-12α-methoxylanosta-7,9(11),24-triene(1), 3ß-hydroxy-12α-methoxy-24-methylene-lanost-7,9(11)-dien(2), 3,7-dioxo-lanosta-8,24-diene(3), and 3,7-dioxo-24-methylene-lanost-8-en(4), were isolated from the latex of Euphorbia resinifera with a variety of chromatography methods. Their structures were elucidated based on spectroscopic data and/or comparison with the data reported in previous research. Compounds 1, 2, and 4 showed moderate inhibition of LPS-induced NO production by RAW264.7, with IC_(50) of 30.4, 37.5, and 28.3 µmol·L~(-1), respectively.


Assuntos
Euphorbia , Triterpenos , Látex , Estrutura Molecular , Esteroides
4.
Toxicon ; 202: 60-66, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34562495

RESUMO

A new guaianolide sesquiterpene lactone with cytotoxic properties was isolated from Euphorbia microsphaera Boiss. To determine the highest active fraction and isolate bioactive compounds, a bioassay guided fractionation approach was used. The general toxicity properties of the plant's extracts and fractions (fr1-10) were assessed against Artemia salina, Oryzeaphilus mercator, and Tribolium castaneum. Cytotoxic activities were investigated against normal human foreskin fibroblasts and two malignant cell lines, including human breast cancer (MCF-7) and human fibrosarcoma cells (HT1080) using the MTT assay at different time points of 24, 48, and 72 h. Single crystal X-ray diffraction (SC-XRD) and mass spectrometry data were used to determine the structure of the active guaianolide sesquiterpene lactone (3aR,4S,4aS,5R,7aS,9aS)-5-hydroxy-5,8-dimethyl-3-methylene-2-oxo-2,3,3a,4,4a,5,6,7,7a, 9a decahydroazuleno [6,5-b] furan-4-yl acetate (named aryanin). Chloroformic fraction 7 (fr7, LC50 = 93.50 µg/mL for general toxicity) had the highest toxicity result, with a mortality rate of more than 50% for both insect species after 12 h at 15 mg/mL. The highest cytotoxicity of aryanin was observed on 24 h treated MCF-7 with an IC50 of 13.81 µg/mL. After 24 h, the inhibition of MCF-7 cell proliferation was 92%-94% at concentrations of 25-50 µg/mL, respectively. On MCF-7, the IC50 was found to be 49.35 µg/mL after 72 h. This compound had a considerable cytotoxicity (IC50 ≤ 12.5 µg/mL, 24 h) on human foreskin fibroblasts. In contrast to the MCF-7 cell line, the proliferation of human foreskin fibroblasts was increased after 72 h.


Assuntos
Antineoplásicos Fitogênicos , Neoplasias da Mama , Euphorbia , Fibrossarcoma , Sesquiterpenos , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Lactonas , Células MCF-7
5.
Molecules ; 26(16)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34443641

RESUMO

Euphorbia species have a rich history of ethnomedicinal use and ethnopharmacological applications in drug discovery. This is due to the presence of a wide range of diterpenes exhibiting great structural diversity and pharmacological activities. As a result, Euphorbia diterpenes have remained the focus of drug discovery investigations from natural products. The current review documents over 350 diterpenes, isolated from Euphorbia species, their structures, classification, biosynthetic pathways, and their structure-activity relationships for the period covering 2013-2020. Among the isolated diterpenes, over 20 skeletal structures were identified. Lathyrane, jatrophane, ingenane, ingenol, and ingol were identified as the major diterpenes in most Euphorbia species. Most of the isolated diterpenes were evaluated for their cytotoxicity activities, multidrug resistance abilities, and inhibitory activities in vitro, and reported good activities with significant half-inhibitory concentration (IC50) values ranging from 10-50 µM. The lathyranes, isopimaranes, and jatrophanes diterpenes were further found to show potent inhibition of P-glycoprotein, which is known to confer drug resistance abilities in cells leading to decreased cytotoxic effects. Structure-activity relationship (SAR) studies revealed the significance of a free hydroxyl group at position C-3 in enhancing the anticancer and anti-inflammatory activities and the negative effect it has in position C-2. Esterification of this functionality, in selected diterpenes, was found to enhance these activities. Thus, Euphorbia diterpenes offer a valuable source of lead compounds that could be investigated further as potential candidates for drug discovery.


Assuntos
Diterpenos/química , Diterpenos/farmacologia , Euphorbia/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Descoberta de Drogas/métodos , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , Relação Estrutura-Atividade
6.
Fitoterapia ; 153: 104989, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34252513

RESUMO

Ten new nortriterpenes, euphorbiumrins A-J (1-10), together with three known analogues (11-13) were isolated from the latex of Euphorbia resinifera. Their structures were established on the basis of extensive spectroscopic analyses (IR, UV, HRESIMS, 1D and 2D NMR). Their inhibitions on tomato yellow leaf curl virus (TYLCV) were evaluated and compound 5 exhibited significant anti-TYLCV activity with an inhibition rate of 71.7% at concentration of 40 µg/mL.


Assuntos
Begomovirus/efeitos dos fármacos , Euphorbia/química , Doenças das Plantas/prevenção & controle , Triterpenos/farmacologia , China , Látex/química , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Doenças das Plantas/virologia , Tabaco/virologia , Triterpenos/isolamento & purificação
7.
Biomed Pharmacother ; 138: 111521, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34311525

RESUMO

Euphorbiae pekinensis Radix (EP) is effective in treating various diseases, but it's toxicity is a major obstacle in use in clinical. Although EP was processed with vinegar to reduce it's toxicity, the detailed mechanism of toxicity in EP have not been clearly delineated. This study investigate the toxicity attenuation-mechanism of Euphorbiae pekinensis after being processed with vinegar (VEP) and the toxic mechanism of four compounds from EP on zebrafish embryos. The contents of four compounds decreased obviously in VEP. Correspondingly, slower development on embryos can be seen as some symptoms like reduction of heart rate, liver area and gastrointestinal peristalsis after exposed to the compounds. Some obvious pathological signals such as pericardial edema and yolk sac edema were observed. Furthermore, the compounds could increase the contents of MDA and GSH-PX and induce oxidative damage by inhibiting the activity of SOD. Also, four compounds could provoke apoptosis by up-regulating the expression level of p53, MDM2, Bax, Bcl-2 and activating the activity of caspase-3, caspase-9. In conclusion, the four compounds play an important role in the toxicity attenuation effects of VEP, which may be related to the apoptosis induction and oxidative damage. This would contribute to the clinical application and further toxicity-reduction mechanism research.


Assuntos
Euphorbia/toxicidade , Trato Gastrointestinal/efeitos dos fármacos , Coração/efeitos dos fármacos , Fígado/efeitos dos fármacos , Compostos Fitoquímicos/toxicidade , Extratos Vegetais/toxicidade , Peixe-Zebra/embriologia , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Cardiotoxicidade , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Embrião não Mamífero/patologia , Euphorbia/química , Trato Gastrointestinal/embriologia , Trato Gastrointestinal/metabolismo , Coração/embriologia , Fígado/embriologia , Fígado/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Compostos Fitoquímicos/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
8.
Phytochemistry ; 190: 112846, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34229224

RESUMO

Euphorbiaceae is one of the largest families of higher plants, including 7500 species, and many of them are used as medicines in China. From 2013 to 2019, a total of 455 previously undescribed diterpenoids were isolated from 53 species of Euphorbia, and some skeleton types were first discovered from the genus Euphorbia. Most of the diterpenoids isolated from Euphorbia spp. have been tested for their biological activity, and some of them were first reported for Euphorbia diterpenoids in recent years, such as neuroprotection, antimalarial activity and inhibition of osteoclast formation. In this review, we summarize all the isolated diterpenoids from the genus Euphorbia according to their skeleton types, classify all these diterpenoids into 26 normal classes and 37 novel skeleton types, and summarize their biological activity.


Assuntos
Diterpenos , Euphorbia , China , Diterpenos/farmacologia , Estrutura Molecular
9.
Phytochemistry ; 190: 112867, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34304117

RESUMO

Eight undescribed diterpenoids, euphorfinoids E-L, together with twelve known analogues, were isolated from the roots of wild Euphorbia fischeriana. Their structures and absolute configurations were elucidated by a combination of NMR, MS, ECD, and X-ray diffraction analyses. The plausible biosynthetic pathway of 1 was also proposed. The isolated compounds displayed moderate inhibitory activity against acetylcholinesterase (AChE) with 50% inhibiting concentration (IC50) values of 6.23-192.38 µM.


Assuntos
Antineoplásicos Fitogênicos , Inibidores da Colinesterase , Diterpenos , Euphorbia , Acetilcolinesterase , Inibidores da Colinesterase/farmacologia , Diterpenos/farmacologia , Estrutura Molecular , Raízes de Plantas
10.
Life Sci ; 280: 119700, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34111465

RESUMO

AIMS: This study evaluated the effect of euphol isolated from Euphorbia umbellata (Pax) Bruyns latex on the activation of complement pathways (classical (CP), alternative (AP) and lectin (LP)), neutrophil chemotaxis, cytotoxic activity, cell morphology and death in HRT-18 and 3T3 cells lines. MAIN METHODS: CP and AP were assessed using hemolytic assays and ELISA for LP; neutrophil chemotaxis was performed using Boyden's chamber; cytotoxicity was evaluated by neutral red methodology and characteristics of cell death were assessed by cell morphology with hematological staining. KEY FINDINGS: Although euphol increased CP activation (38% at a concentration of 976.1 µM), an inhibitory effect on AP, LP (31% and 32% reduction in the concentration of 976.1 µM) and neutrophil chemotaxis (inhibit 84% of neutrophil migration at a concentration 292.9 µM) was observed. In addiction euphol was able to induce significant cell death in a time-dependent manner, presenting an IC50 of 70.8 µM and 39.2 µM for HRT-18 and 3T3 cell lines respectively and it was also observed apoptotic characteristics as cellular rounding, chromatin condensation and blebs formation for both cell lines. SIGNIFICANCE: Euphol has a potential use for the treatment of complement-related inflammatory diseases due to its ability to downregulate inflammation. On the other hand, the controlled activation of CP can contribute to complement-dependent cytotoxicity in the context of monoclonal antibody-based cancer treatment.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Ativação do Complemento/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Lanosterol/análogos & derivados , Células 3T3 , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Euphorbia/química , Humanos , Lanosterol/farmacologia , Camundongos , Neoplasias/tratamento farmacológico
12.
Fitoterapia ; 153: 104966, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34144143

RESUMO

Euphorboside A (1), an unusual meroterpenoid glycoside featuring the incorporation of an acylphloroglucinol moiety into a humulene skeleton to form a 6/6/11 ring system, was isolated from the roots of Euphorbia kansuensis. Its structure was elucidated by extensive spectroscopic analysis, chemical methods, and ECD calculations. Compound 1 was screened for the cytotoxicity against nine cancer cell lines, and 1 showed marked inhibitory activities against human colon cancer RKO and human breast cancer MDA-MB-231 cell lines with IC50 values of 3.70 and 4.15 µM, respectively.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Euphorbia/química , Glicosídeos/farmacologia , Sesquiterpenos Monocíclicos/química , Floroglucinol/química , Terpenos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , China , Glicosídeos/isolamento & purificação , Humanos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Raízes de Plantas/química , Terpenos/isolamento & purificação
13.
ACS Appl Mater Interfaces ; 13(27): 32332-32342, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34190527

RESUMO

In nature, many extant species exhibit functionalized surface structures during evolution. In particular, wettability affects the functionalization of the surface, and nano/microstructures have been found to enable functions, such as droplet jumping, thereby making self-cleaning, antifog, antibacterial, and antireflection surfaces. Important efforts are underway to understand the surface structure of plant leaves and establish rational design tools for the development of new engineering materials. In this study, we focused on the hierarchical nano/microstructure of the leaves of Euphorbia myrsinites (hereinafter, E. myrsinites), which has a hierarchical shape with microsized papillae, covered with nanosized protruding wax, and observed the condensation behavior on the leaf surface. Si is vertically etched via reactive ion etching (RIE) to artificially mimic the hierarchical nano/microstructures on the leaves of E. myrsinites. We made four types of artificial hierarchical structures, with micropillars having pillar diameters of 5.6 and 16 µm (pillar spacing of 20 and 40 µm, respectively) and heights of 6.5 and 19.5 µm, and nanopillars formed on the surface. The optical observation with a microscope revealed a very high density of condensed droplets on the artificial surface and a stable jumping behavior of droplets of 10 µm or more. Furthermore, in the samples with a micropillar diameter of 5.6 µm and a micropillar height of 19.5 µm, the droplets that had jumped and fallen thereupon bounced off, thereby preventing reattachment. As a result, no droplets of 35 µm or more could exist even after 10 min. In addition, it was clear that a small underlying droplet of less than 10 µm was generated at the bottom of the relatively large secondary droplet existing on the large micropillar of 16 µm, and a frequent coalescence of the droplets occurred. This study revealed the phenomenon of condensation on the surface of plants as well as made it possible to improve the heat exchange process by significantly promoting the heat transfer of condensation using artificial surfaces.


Assuntos
Biomimética/métodos , Euphorbia , Hidrodinâmica , Molhabilidade
14.
J Org Chem ; 86(11): 7588-7593, 2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-34014670

RESUMO

Compounds 1-3, the rare examples of 9,11-seco euphane or lanostane triterpenoids featuring an enol-hemiacetal functionality, were isolated from Euphorbia stracheyi. Their structures were elucidated by a combination of spectroscopic, computational, chemical, and single-crystal X-ray diffraction means, which enables the structure of previously published euphorol J to be revised as 1. 1-3 showed significant cytotoxicities on the breast cancer cell line MDA-MB-468 with IC50 values in the range of 2.9-3.9 µM.


Assuntos
Euphorbia , Triterpenos , Cristalografia por Raios X , Estrutura Molecular , Esteroides , Triterpenos/farmacologia
15.
Chem Biodivers ; 18(7): e2100238, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34033700

RESUMO

Plants belonging to Euphorbia L. genus are considered very interesting from a medicinal point of view due to their diverse metabolites and bioactivities. The essential oil (EO) of Euphorbia mauritanica L. is not studied up to date. Therefore, the present study aimed to explore the chemical profile of this EO and evaluate its antioxidant, cytotoxic, and allelopathic potentialities. The EO was extracted from the whole plant via hydrodistillation and then, analyzed by gas chromatography/mass spectrometry (GC/MS). The correlation of E. mauritanica with the other Euphorbia plants was established using chemometric analysis. The antioxidant activity was determined based on scavenging of the free radical, 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). The anti-proliferation of the EO on the Hep G2 and MCF-7 cells was evaluated. Finally the allelopathic activity of the EO was assessed against the two noxious weeds, Dactyloctenium aegyptium and Urospermum picroides. Forty-one compounds were identified using GC/MS analysis, with an abundance of terpenoids (91.54 %) that were categorized into mono- (30.75 %), sesqui- (15.23 %), and diterpenes (45.56 %). Interestingly, the results revealed the preponderance of diterpenoid constituents although they are rarely found in the EOs of the plant kingdom. The major compounds were (3E)-cembrene A (18.66 %), verticiol (17.05 %), limonene (7.91 %), eucalyptol (7.26 %), α-pinene (5.61 %), neo-cembrene A (3.52 %), kaur-16-ene (3.24 %), and cembrene (3.09 %). The EO showed moderate antioxidant activity where it attained IC50 values of 83.34 and 64.21 µg mL-1 for DPPH and ABTS compared to 23.01 and 19.23 µg mL-1 for ascorbic acid as standard, respectively. The EO exhibited very weak cytotoxic effect on MCF-7 and Hep G2 cells. The EO showed significant allelopathic activities against the weeds D. aegyptium and U. picroides in a concentration-dependent manner. EO was found more effective against U. picroides than D. aegyptium with IC50 values of 0.79, 0.45, and 0.67 mg mL-1 and 1.17, 0.55, and 1.08 mg mL-1 for germination, root, and shoot growth, respectively. Due to the high content of diterpenes in E. mauritanica, further study is recommended for more characterization of pure forms of the identified diterpenes as well as evaluating their bioactivity either solely or synergistically.


Assuntos
Alelopatia/efeitos dos fármacos , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Diterpenos/farmacologia , Euphorbia/química , Óleos Voláteis/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Benzotiazóis/antagonistas & inibidores , Compostos de Bifenilo/antagonistas & inibidores , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Diterpenos/química , Diterpenos/isolamento & purificação , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Picratos/antagonistas & inibidores , Ácidos Sulfônicos/antagonistas & inibidores , Células Tumorais Cultivadas
16.
Bioorg Chem ; 112: 104944, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33962090

RESUMO

Twelve previously undescribed diterpenoids, euplarisans A-L (1-12), including one premyrsinane and eleven lathyranes, along with ten known analogues 13-22 were isolated from the seeds of Euphorbia lathyris. Their chemical structures were delineated by spectroscopic analysis and single-crystal X-ray diffraction. Interestingly, both 5 and 6 possessed an unusual trans-gem-dimethylcyclopropane as structural features and compound 8 was elucidated as premyrsinane-type diterpenoid. Meanwhile, a plausible biogenetic pathway for compounds 1-12 was proposed. In the anti-inflammatory bioassay, compounds 1, 2, 4, 13, 16, and 18 markedly inhibited the nitric oxide production in LPS-induced RAW264.7 macrophage cells. Compound 1 showed a more remarkable anti-inflammatory effect than others. It inhibited the generation of inflammatory cytokines (IL-1ß, IL-6, and TNF-α) and also obviously decreased the expression of iNOS, COX-2, and p-IκBα in a dose-dependent manner. The structure-activity relationships (SARs) of these diterpenoids were also discussed.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Diterpenos/farmacologia , Euphorbia/química , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/antagonistas & inibidores , Citocinas/biossíntese , Diterpenos/química , Diterpenos/isolamento & purificação , Relação Dose-Resposta a Droga , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Células RAW 264.7 , Sementes/química , Relação Estrutura-Atividade
17.
Bioorg Chem ; 112: 104989, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34022709

RESUMO

Eight new jatrophane diterpenoids, Euphosorophane F-M (1-8), as well as fourteen known jatrophane diterpenoids (9-22) were separated and purified from the fructus of Euphorbia sororia, and the chemical structures were determined based on extensive spectroscopic analysis, 1D, 2D NMR and HRESIMS data included. Their absolute configurations of compounds 1, 2, 9, and 22 were elucidated by X-ray crystallographic analysis. These jatrophane diterpenoids showed lower cytotoxicity and compounds 3, 4, 11, 12, 13, 14, and 20 revealed promising multidrug resistance (MDR) reversal ability as modulators compared to verapamil (VRP) by MTT assay. The structure-activity relationship (SAR) exhibited that the absence of keto-carbonyl at C-9 and C-14 was essential to MDR reversal activity and the acyloxies substitution at C-5, C-7, C-8, and C-14 also made the activity difference. Euphosorophane I (4) particularly unfold greater potency (EC50 = 1.82 µM) in reversing P-gp-mediated resistance to doxorubicin (DOX). As shown by fluorescence microscopy, 4 promoted intracellular accumulation of rhodamine 123 (Rh123) and DOX in a dose-dependentmanner than VRP. Flow cytometry indicated that 4 inhibitedP-glycoprotein (P-gp) -dependentRh123 efflux in drug-resistant MCF-7/ADR cells. 4 stimulated P-gp-ATPase activity in a concentration-dependent way and inhibited DOX transport activity. Western blot and real-time qPCR results further illustrated that 4 exhibited superior MDR reversal effect in MCF-7/ADR cells attributed to the activation of ATPase rather than the upregulation of P-gp expression and mRNA levels. In addition, 4 bond to the drug-binding site of P-gp predicted by the molecular docking analysis. Collectively, these results indicated that 4 efficiently reversed P-gp-mediated MDR via inhibiting the ABCB1 drug efflux function. 4 with the advantage of low toxicity and efficient could be used as an adjuvanttherapy drug for breast cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Diterpenos/farmacologia , Euphorbia/química , Subfamília B de Transportador de Cassetes de Ligação de ATP/antagonistas & inibidores , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Diterpenos/química , Diterpenos/isolamento & purificação , Relação Dose-Resposta a Droga , Doxorrubicina/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Células MCF-7 , Microscopia de Fluorescência , Modelos Moleculares , Estrutura Molecular , Relação Estrutura-Atividade , Células Tumorais Cultivadas
18.
BMC Ecol Evol ; 21(1): 102, 2021 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-34049497

RESUMO

BACKGROUND: The Euphorbia hypothesis on the origin of fairy circles (FCs) in Namibia dates back to 1979. It proposes that the remains of decaying shrubs would induce an allelopathic interaction with the grasses and thereby cause bare-soil FCs. Here, we investigated this hypothesis based on revisiting marked Euphorbias after four decades, comparing the typical size distribution of dead Euphorbia damarana and FCs, and analyzing the spatial patterns of Euphorbias and FCs within the same drone-mapped study plots in three regions of Namibia. RESULTS: We found four dead Euphorbias in the southern Giribes that were marked by G.K. Theron about 40 years ago. Those locations did not develop into FCs over this time span. However, for the four dead Euphorbias, we provide photographic evidence that grass tufts were growing at the metal pins of those decaying shrubs, agreeing with previous research findings that the soil taken from beneath dead E. damarana shrubs was stimulating rather than inhibiting the growth of grasses. In the Giribes, there were very large FCs that ranged in diameter from 13.0 to 19.1 m. By contrast, the measured dead E. damarana, including the largest plants that we could find, ranged in size only between 4.2 and 11.7 m. At Brandberg, we found particularly small FCs with diameters between 2.4 and 2.7 m but the dead E. damarana, including the smallest dead shrubs in the area, ranged in size between 4.1 and 7.2 m. Hence given these size mismatches, the decaying Euphorbias cannot induce such observed FCs in the two regions. Spatial patterns of E. damarana and FCs in the two regions Giribes and Brandberg, as well as of E. gummifera and FCs near Garub, showed a strong mismatch within the same habitat: in four out of five plots the patterns differed significantly. FCs were regularly distributed while Euphorbias were predominantly clustered. CONCLUSIONS: We reject the Euphorbia hypothesis based on the fact that grass growth was not prevented under decaying shrubs, the size of dead Euphorbias cannot explain the size of observed FCs and the spatial distribution of Euphorbias cannot cause the specific pattern signature of FCs.


Assuntos
Euphorbia , Ecossistema , Namíbia , Poaceae , Solo
19.
Phytochemistry ; 188: 112775, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34015626

RESUMO

Bioassay-guided purification on the ethanolic extract of the roots of Euphorbia kansui Liou ex S.B.Ho (Euphorbiaceae) led to the isolation of one unreported ingenane-type (euphorksol A) and six unreported jatrophane-type (euphorksjats A-F) diterpenoids, together with twenty-five known diterpenoids. Their structures were elucidated based on extensive NMR analysis and high-resolution mass spectrometry. Euphorksol A is a rare example of an ingenane-type diterpenoid with a 6,7-expoxy fragment. All compounds were examined for cytotoxicity against adriamycin (Adr)-sensitive HepG-2 and Adr-resistant HepG-2/Adr cell lines, but none showed significant activity. Then, all isolates were evaluated for their ability to reverse multidrug resistance (MDR). 6ß,7ß-Epoxy-3ß,4ß,5ß-trihydroxyl-20- deoxyingenol and 3,5,7,15-tetraacetoxy-9-nicotinoyloxy-14-oxojatropha-6(17),11-diene showed significant MDR reversal activity in HepG-2/Adr cells (reversal fold: RF = 186.4 and 143.8, respectively) versus the positive control verapamil (Ver, RF = 93.7). Euphorksol A and kansuinin B exhibited moderate MDR reversal activity (RF = 57.4 and 68.9, respectively). These compounds are the first ingenane-type diterpenoids reported to show MDR reversal activity, which will provide new insights toward the development of MDR regulatory agents.


Assuntos
Diterpenos , Euphorbia , Diterpenos/farmacologia , Resistência a Múltiplos Medicamentos , Estrutura Molecular
20.
J Chem Ecol ; 47(6): 564-576, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33881708

RESUMO

Based on the hypothesis that the variation of the metabolomes of latex is a response to selective pressure and should thus be affected differently from other organs, their variation could provide an insight into the defensive chemical selection of plants. Metabolic profiling was used to compare tissues of three Euphorbia species collected in diverse regions. The metabolic variation of latexes was much more limited than that of other organs. In all the species, the levels of polyisoprenes and terpenes were found to be much higher in latexes than in leaves and roots of the corresponding plants. Polyisoprenes were observed to physically delay the contact of pathogens with plant tissues and their growth. A secondary barrier composed of terpenes in latex and in particular, 24-methylenecycloartanol, exhibited antifungal activity. These results added to the well-known role of enzymes also present in latexes, show that these are part of a cooperative defense system comprising biochemical and physical elements.


Assuntos
Euphorbia/metabolismo , Euphorbia/microbiologia , Geografia , Herbivoria , Látex/metabolismo , Metabolômica , Euphorbia/fisiologia , Especificidade da Espécie
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...