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1.
Fitoterapia ; 137: 104285, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31386897

RESUMO

Botanical-based natural products are an important resource for medicinal drug discovery and continue to provide diverse pharmacophores with therapeutic potential against cancer and other human diseases. A prototype Traditional Chinese Medicine (TCM) plant extract library has been established at the US National Cancer Institute, which contains both the organic and aqueous extracts of 132 authenticated medicinal plant species that collectively represent the potential therapeutic contents of most commonly used TCM herbal prescriptions. This library is publicly available in 96- and 384- well plates for high throughput screening across a broad array of biological targets, as well as in larger quantities for isolation of active chemical ingredients. Herein, we present the methodology used to generate the library and the preliminary assessment of the anti-proliferative activity of this crude extract library in NCI-60 human cancer cell lines screen. Particularly, we report the chemical profiling and metabolome comparison analysis of four commonly used TCM plants, namely Brucea javanica, Dioscorea nipponica, Cynanchum atratum, and Salvia miltiorrhiza. Bioassay-guided isolation resulted in the identification of the active compounds, and different extraction methods were compared for their abilities to extract cytotoxic compounds and to concentrate biologically active natural products.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Plantas Medicinais/química , Antineoplásicos Fitogênicos/isolamento & purificação , Brucea/química , Linhagem Celular Tumoral , China , Cynanchum/química , Dioscorea/química , Descoberta de Drogas , Humanos , Medicina Tradicional Chinesa , National Cancer Institute (U.S.) , Compostos Fitoquímicos/isolamento & purificação , Salvia miltiorrhiza/química , Estados Unidos
2.
Fitoterapia ; 137: 104287, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31386898

RESUMO

Phytochemical investigation of the fruit of Crataegus pinnatifida led to the isolation of four pairs of dihydrobenzofuran neolignan enantiomers (1a/1b-4a/4b) including six new compounds (1a/1b, 2a/2b, 3a and 4a). The enantioseparations of the racemates were achieved successfully by chiral chromatographic column. Their structures were established by comprehensive spectroscopic analyses and the absolute configurations were determined by quantum mechanical calculation of electronic circular dichroism (ECD) spectra. All compounds were evaluated in vitro for their cytotoxicity using human hepatocellular carcinoma Hep3B and HepG2 cells. Among them, it was found that 2a had a selective cytotoxicity against Hep3B cells with IC50 value of 25.47 µM, while the IC50 value of its enantiomer 2b on Hep3B cells was 59.37 µM. These results implied that the absolute configurations of 2a and 2b possessed remarkable influences on their cytotoxicity. Further flow cytometry analysis indicated that 2a performed more significant effect on cell apoptosis compared with its enantiomer 2b.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Crataegus/química , Frutas/química , Lignanas/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , China , Células Hep G2 , Humanos , Lignanas/isolamento & purificação , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Estereoisomerismo
3.
Chem Pharm Bull (Tokyo) ; 67(7): 654-665, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31257321

RESUMO

Quassinoids, one kind of triterpenoids with multiple bioactivities such as anti-cancer, anti-malarial, anti-oxidative, anti-microbial, anti-diabetic, anti-viral, and anti-inflammatory effects, have drawn much attention in recent years. Between 2004 and 2018, the structural characteristics and plant sources of 190 quassinoids were reported. Herein, the structure-activity relationships (SARs) of quassinoids along with the anti-cancer mechanisms of four representative quassinoids, eurycomanone, bruceine D, dehydrobruceine B, and brusatol are discussed. This review might be useful for further research and development of quassinoids.


Assuntos
Antineoplásicos Fitogênicos/química , Quassinas/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Antiprotozoários/química , Antiprotozoários/isolamento & purificação , Antiprotozoários/farmacologia , Antivirais/química , Antivirais/isolamento & purificação , Antivirais/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Humanos , Plantas/química , Plantas/metabolismo , Plasmodium falciparum/efeitos dos fármacos , Quassinas/isolamento & purificação , Quassinas/farmacologia , Relação Estrutura-Atividade , Vírus do Mosaico do Tabaco/efeitos dos fármacos
4.
Ceska Slov Farm ; 68(2): 48-68, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31331175

RESUMO

This review deals with cytotoxic and antiproliferative activity of fifty seven prenylated phenols isolated from Morus alba. Prenyl side chain, which can be variously modified, increases lipophilicity of the substances, thereby improving their penetration through biological membranes and thus results in an increased bioavailability. The objective was to describe the relationship between structure of the prenylated phenols and their cytotoxic effect and to clarify various mechanisms by which cytotoxic prenylated phenols induce apoptosis. The conclusions showed that the cytotoxicity of the substances increases with increasing number of the prenyl side chains and ketal groups. Conversely, modification of the prenyl side chain, such as hydroxylation, reduces cytotoxicity. The cytotoxic activity is also influenced by the presence of prenyl and hydroxyl groups at specific positions.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Citotoxinas/farmacologia , Morus/química , Fenóis/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Citotoxinas/isolamento & purificação , Estrutura Molecular , Fenóis/isolamento & purificação , Prenilação
5.
Chem Biodivers ; 16(8): e1900317, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31264344

RESUMO

Four new diterpenoids named cuceolatins A-D, including three labdane-type (1-3) and one abietane-type (4) as well as three known labdane analogs (5-7), were reported from the leaves of Cunninghamia lanceolata. Structural assignments for these compounds were conducted by analyses of spectroscopic data, and their absolute configurations were determined by time-dependent density functional theory (TD-DFT) based electronic circular dichroism (ECD) calculations. Among them, the abietane-type diterpenoid (11-hydroxy-12-methoxyabieta-8,11,13-trien-3-one (4)) showed significant cytotoxicity against human MDA-MB-231, MCF-7, and HeLa tumor cell lines with IC50 measurements of 4.3, 2.8 and 4.5 µm, respectively, while the labdane-type diterpenoids with a 4α-carboxy group (1-3 and 5) exhibited moderate antibacterial activity towards Bacillus subtilis and Staphylococcus aureus with IC50 values all below 25 µm.


Assuntos
Cunninghamia/química , Diterpenos/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dicroísmo Circular , Cunninghamia/metabolismo , Teoria da Densidade Funcional , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Diterpenos de Abietano/química , Diterpenos de Abietano/isolamento & purificação , Diterpenos de Abietano/farmacologia , Humanos , Conformação Molecular , Folhas de Planta/química , Folhas de Planta/metabolismo , Staphylococcus aureus/efeitos dos fármacos
6.
Zhongguo Zhong Yao Za Zhi ; 44(10): 2096-2101, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31355567

RESUMO

The chemical constituents from the stems and leaves of Clausena emarginata were separated and purified by column chromatographies on silica gel,ODS,Sephadex LH-20,and PR-HPLC. The structures of the isolated compounds were identified on the basis of physicochemical properties and spectroscopic analysis,as well as comparisons with the data reported in the literature. Sixteen compounds were isolated from the 90% ethanol extract of the stems and leaves of C. emarginata,which were identified as siamenol( 1),murrastanine A( 2),3-formyl-1,6-dimethoxycarbazole( 3),3-methoxymethylcarbazole( 4),3-methylcarbazole( 5),murrayafoline A( 6),3-formylcarbazole( 7),3-formyl-1-hydroxycarbazole( 8),3-formyl-6-methoxycarbazole( 9),murrayanine( 10),murrayacine( 11),girinimbine( 12),nordentatin( 13),chalepin( 14),8-hydroxy-6-methoxy-3-pentylisocoumarin( 15) and ethyl orsellinate( 16). Compounds 1-4,14-16 were isolated from C. emarginata for the first time. Among them,compounds 1,2,15 and 16 were isolated from the genus Clausena for the first time. All isolated compounds were evaluated for their cytotoxic activities against five human cancer cell lines: HL-60,SMMC-7721,A-549,MCF-7 and SW480 in vitro. Compounds 12 and 14 showed significant inhibitory effects against various human cancer cell lines with IC_(50) values comparable to those of doxorubicin.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Clausena/química , Compostos Fitoquímicos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Doxorrubicina , Humanos , Compostos Fitoquímicos/isolamento & purificação , Folhas de Planta/química , Caules de Planta/química
7.
Zhongguo Zhong Yao Za Zhi ; 44(11): 2274-2277, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31359653

RESUMO

Two sesquiterpenes were isolated from the agarwood originating from Gyrinops salicifolia with various chromatographic techniques, and their structures were determined as 12-hydroxy-dihydrocyperolone(1) and(rel)-4ß,5ß,7ß-eremophil-9-en-12,8α-olide(2), through a combined analysis of physicochemical properties and spectroscopic evidence. Compound 1 was a new compound. Compound 2 showed cytotoxicities against K562 and BEL-7401 cell lines, with IC_(50) values of(17.85±0.04) and(21.82±0.07) mg·L~(-1), respectively [taxol as positive control, with IC_(50) values of(1.97±0.11) and(6.31±0.08) mg·L~(-1)].


Assuntos
Sesquiterpenos/farmacologia , Thymelaeaceae/química , Madeira/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Humanos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Sesquiterpenos/isolamento & purificação
8.
Zhongguo Zhong Yao Za Zhi ; 44(11): 2278-2282, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31359654

RESUMO

Fourteen chemical constituents, including 5-hydroxy-4-methoxy-1-tetralone(1), 4,8-dihydroxy-1-tetralone(2), 4,5-dihydroxy-α-tetralone(3), blumenol B(4), dehydrovomifoliol(5), megastigm-5-ene-3,9-diol(6), juglanin B(7), blumenol C(8), loliolide(9), oleracone B(10), syringarsinol(11), pinoresinol(12), methyl 4-hydroxy-3-methoxybenzoate(13), and isovanillic acid(14), were isolated from the dichloromethane fraction of 95% methanol extract of green walnut husks by silica gel and MCI column chromatography, and Pre-HPLC. Their structures were determined by spectroscopic methods, such as NMR, MS and so on. Among them, compounds 1, 4-6, 8-13 were isolated from the green walnut husks for the first time, and compounds 4-6, 8, 10, 12, 13 were isolated from the Juglans genus for the first time. All of isolates were detected their inhibitory activities against HeLa, HGC-27 and Ht-29 cell lines by the MTT assay. The result showed that compounds 2, 3, 7, 9 and 11 exhibited inhibitory activity against the tested cell line. The IC_(50) of 7 were 26.5, 9.0, 25.4 µmol·L~(-1), respectively.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Juglans/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Antineoplásicos Fitogênicos/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Células HT29 , Células HeLa , Humanos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação
9.
Fitoterapia ; 137: 104262, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31284018

RESUMO

Eight undescribed 9,19-cycloartane type triterpenoid glycosides (cimdalglnoside A-H) and ten known analogues were obtained from the phytochemical research on the roots of Actaea dahurica (syn. Cimicifuga dahurica). All compounds were characterised by spectroscopic experiments, and chemical method. All the compounds isolated were assayed for cytotoxicity to five human cancer cell lines. Cimdalglnoside G showed promising cytotoxicities against Hela, and MCF-7 cell lines with IC50 values at 7.7 and 12.2 µM.


Assuntos
Actaea/química , Glicosídeos/farmacologia , Raízes de Plantas/química , Triterpenos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , China , Glicosídeos/isolamento & purificação , Células HeLa , Humanos , Células MCF-7 , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Triterpenos/isolamento & purificação
10.
Fitoterapia ; 137: 104261, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31284019

RESUMO

Three new sesquilignans, zijusesquilignans A-C (1-3), together with fifteen known compounds (4-18), were isolated from fruits of Ziziphus jujuba var. inermis Rehder (Rhamnaceae). Their chemical structures were established using spectroscopic analyses including 1D- and 2D-NMR, HR-EIMS, and ECD spectra. These compounds were assessed for their inhibitory effects on nitric oxide (NO) production. Of these compounds, 1-3 and 17 displayed inhibitory effects on NO production, with IC50 values ranging from 18.1 to 66.4 µM. Pretreatment with 1 and 17 significantly suppressed LPS-induced expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein in cells. Moreover, compounds 1-3, 7, 9, and 17 exhibited cytotoxic activities against three human tumor cell lines, with IC50 values ranging from 8.4 to 44.9 µM.


Assuntos
Anti-Inflamatórios/farmacologia , Frutas/química , Lignanas/farmacologia , Ziziphus/química , Animais , Anti-Inflamatórios/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Ciclo-Oxigenase 2/metabolismo , Humanos , Lignanas/isolamento & purificação , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Células RAW 264.7 , República da Coreia
11.
Fitoterapia ; 137: 104264, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31299275

RESUMO

Five undescribed triterpene-type saponins, parkibicolorosides A-E, a cassane-type diterpene, and a known trimethoxy benzene glucoside were isolated from the roots of Parkia bicolor A. Chev. Their structures were elucidated by different spectroscopic methods including 1D- and 2D-NMR experiments as well as HR-ESI-MS analysis. Their cytotoxic activity against the chronic myeloid leukemia (K562) cell line was evaluated. The monosaccharides saponins exhibited a moderate antiproliferative activity with IC50 ranging from 48.49 ±â€¯0.16 to 81.66 ±â€¯0.17 µM.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Fabaceae/química , Raízes de Plantas/química , Saponinas/farmacologia , Triterpenos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Costa do Marfim , Humanos , Células K562 , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Saponinas/isolamento & purificação , Triterpenos/isolamento & purificação
12.
Fitoterapia ; 137: 104268, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31306720

RESUMO

Solanum nigrum L. (also called as European black nightshade) has been traditionally used as folk medicine and food in some regions. Phytochemical investigations of the immature fruits of S. nigrum yielded five steroidal alkaloid glycosides (1-5), including an unprecedented nor-spirosolane type steroidal alkaloid with a five-membered ring A (1) and two novel spirosolane type steroidal alkaloid glycosides (2, 3), together with eight known phenolic compounds (6-13). Their structures were elucidated on the basis of spectroscopic and chemical methods, including IR, NMR, HR-ESI-MS, and GC analyses. Five steroidal alkaloid glycosides were tested for their potential antiproliferative effects against HL-60, U-937, Jurkat, K562, and HepG2 cell lines and inhibitory activities on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in a macrophage cell line RAW 264.7. Compound 1 exhibited significant inhibition on NO production with an IC50 value of 23.4 ±â€¯2.0 µM, compared to positive control indomethacin (IC50, 47.40 ±â€¯4.50 µM). Compound 4 exhibited significant cytotoxicity against all tested cell lines.


Assuntos
Alcaloides/farmacologia , Glicosídeos/farmacologia , Solanum nigrum/química , Esteroides/farmacologia , Alcaloides/isolamento & purificação , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , China , Frutas/química , Glicosídeos/isolamento & purificação , Humanos , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Células RAW 264.7 , Esteroides/isolamento & purificação
13.
Fitoterapia ; 137: 104275, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31351126

RESUMO

The non-small cell lung cancer (NSCLC) represents a malignant type of cancer worldwide. The atalantraflavone (AFL) is a natural product isolated from leaves of Atalantia monophylla (L.) DC. However, the function of atalantraflavone in NSCLC is still elusive. In present work, we have unraveled a novel function of AFL in NSCLC. AFL significantly inhibited NSCLC cell viability and colony formation. AFL increased sub-G1 fraction and apoptotic rates in a dose-dependent manner. Furthermore, Twist-related protein 1 (Twist1) was identified as the target of AFL. The association between AFL and Twist1 markedly decreased the stability of Twist1 via elevated ubiquitin mediated proteasomal degradation. AFL induced NSCLC suppression was mediated by Twist1 as Twist1 overexpression could partially reverse the inhibitory effect of AFL on migration and metastasis. Furthermore, AFL could also sensitize NSCLC cells to cisplatin treatment and consistently impair NSCLC proliferation and metastasis. Our current data have identified a tumor suppressive function for AFL in NSCLC by increasing Twist1 degradation. Therefore, the anti-tumor activity of AFL might provide critical insight into pharmaceutic lung cancer intervention to overcome cisplatin resistance.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Flavonas/farmacologia , Proteínas Nucleares/antagonistas & inibidores , Rutaceae/química , Proteína 1 Relacionada a Twist/antagonistas & inibidores , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Linhagem Celular Tumoral , Cisplatino , Resistencia a Medicamentos Antineoplásicos , Flavonas/isolamento & purificação , Humanos , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Folhas de Planta/química , Estabilidade Proteica
14.
Nat Chem Biol ; 15(7): 747-755, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31209351

RESUMO

Nimbolide, a terpenoid natural product derived from the Neem tree, impairs cancer pathogenicity; however, the direct targets and mechanisms by which nimbolide exerts its effects are poorly understood. Here, we used activity-based protein profiling (ABPP) chemoproteomic platforms to discover that nimbolide reacts with a novel functional cysteine crucial for substrate recognition in the E3 ubiquitin ligase RNF114. Nimbolide impairs breast cancer cell proliferation in-part by disrupting RNF114-substrate recognition, leading to inhibition of ubiquitination and degradation of tumor suppressors such as p21, resulting in their rapid stabilization. We further demonstrate that nimbolide can be harnessed to recruit RNF114 as an E3 ligase in targeted protein degradation applications and show that synthetically simpler scaffolds are also capable of accessing this unique reactive site. Our study highlights the use of ABPP platforms in uncovering unique druggable modalities accessed by natural products for cancer therapy and targeted protein degradation applications.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Produtos Biológicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Proteínas de Transporte/metabolismo , Limoninas/farmacologia , Proteólise/efeitos dos fármacos , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Limoninas/química , Limoninas/isolamento & purificação
15.
Chem Biodivers ; 16(7): e1900189, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31222938

RESUMO

The aim of this study was to evaluate the ethanolic extract of propolis originated from northern Turkey for its antiproliferative, apoptotic and cell cycle arrest promoting effects on MCF7, HGC27, A549 cancer cell lines and a healthy cell line (HUVEC) in terms of DNA content, morphological features, expression of cell cycle checkpoint proteins p21, p53, Cyclin D1 and immune checkpoint protein PD-L1. The extract showed moderate antiproliferative activity against all tested cancer cell lines with IC50 values in the range of 58.6-90.7 µg/mL in MTS assay. Further studies indicated that propolis extract exerted apoptotic effect on cancer cell lines, promoted cell cycle arrest through activation of p21 and resulted in accumulation at G0/G1 phase of cancer cells. Propolis treatment caused increased cell size, according to fluorescent imaging except for MCF7. HPTLC analysis revealed that 3-O-methylquercetin, chrysin, caffeic acid, CAPE, galangin and pinocembrin were the main components of the extract. The amounts of caffeic acid and CAPE in the extract were found to be 5.5 and 11.1 mg/g, respectively, by a validated HPLC method. Our study is the first one, revealing effect of propolis on PD-L1 expression on certain cancer cell lines.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Extratos Vegetais/farmacologia , Própole/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Relação Estrutura-Atividade , Turquia
16.
Phytochemistry ; 165: 112047, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31203102

RESUMO

Four undescribed lignans and two undescribed sesquiterpenic acids, together with three known compounds (hypochoeroside C, hypochoeroside D, and 5-O-caffeoylshikimic acid) were isolated from the roots of Hypochaeris radicata subsp. neapolitana (Asteraceae, Cichorieae). The lignans were identified as 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-ß-D-glucopyranoside, 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-ß-D-glucopyranosyl-2'-O-methacrylate, (7S,8R,8'R)-7-(3,4-dihydroxyphenyl)-3',4'-dihydroxy-7,8,7',8'-tetrahydronaphtho [8,8'-c]furan-1(3H)-one, and (7S,8R,8'R)-7-(3,4-dihydroxyphenyl)-3',4'-dihydroxy-8'-(hydroxymethyl)-7,8,7',8'-tetrahydronaphthalen-8-carboxylic acid. The two sesquiterpenic acids were identified as the ring open precursors of hypochoerosides C and D. Structures were elucidated using NMR and HRMS. Absolute configurations of (7S,8R,8'R)-7-(3,4-dihydroxyphenyl)-3',4'-dihydroxy-7,8,7',8'-tetrahydronaphtho [8,8'-c]furan-1(3H)-one and (7S,8R,8'R)-7-(3,4-dihydroxyphenyl)-3',4'-dihydroxy-8'-(hydroxymethyl)-7,8,7',8'-tetrahydronaphthalen-8-carboxylic acid were determined using electronic circular dichroism (ECD) spectroscopy. 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-ß-D-glucopyranoside was evaluated for its anti-proliferative activity against myeloma cell lines MM1S, U266, and NCI-H929 and showed cytotoxicity at 100 mM against MM1S strain. No neurotoxicity was observed for major compounds 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-ß-D-glucopyranoside, hypochoeroside C, and hypochoeroside D in a fluorescence assay measuring neurite outgrowth in dorsal root ganglion (DRG) neurons. Additionally, compounds 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-ß-D-glucopyranoside, hypochoeroside C, hypochoeroside D, and hypochoerosidic acid D were quantified in unstressed and drought-stressed plants using HPLC-DAD. Drought-stressed plants were found to contain lower concentrations of the lignan 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-ß-D-glucopyranoside and sesquiterpene lactone hypochoeroside C.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Asteraceae/química , Lactonas/farmacologia , Lignanas/farmacologia , Mieloma Múltiplo/tratamento farmacológico , Sesquiterpenos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lactonas/química , Lactonas/isolamento & purificação , Lignanas/química , Lignanas/isolamento & purificação , Estrutura Molecular , Mieloma Múltiplo/patologia , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Relação Estrutura-Atividade
17.
Phytochemistry ; 164: 172-183, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31158602

RESUMO

Screening assays showed that total glycoside-rich fraction (TG) of rhizomes of Polygonatum sibiricum unveiled remarkable anti-proliferative activities against three cancer cell lines (A549, HepG2, and Caco2). Activity-guided isolation of TG afforded seven undescribed steroidal glycosides (polygonosides 1-7), along with 24 known glycosides. Their structures were established by 1D and 2D NMR spectroscopic analyses, high-resolution mass spectrometry, and chemical evidence. The isolated steroidal glycosides were tested for their antiproliferative activities against A549, HepG2, and Caco2 cells. Compounds 8, 10, 11, and 16 possessed stronger anticancer activities against A549 cells than the positive control Bay (25.8 µM), with IC50 values ranging from 5.8 to 24.2 µM. Compound 10 reduced the expression of Blc-2 and pro-caspase3 and increased the production of Bax as determined by western blotting. Molecular docking experiment suggested that 10 bound stably to the BH3-binding groove of the Bcl-2 protein by hydrogen bond interactions. These compounds could be candidates for anticancer agents with cytotoxic activity.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Glicosídeos/farmacologia , Polygonatum/química , Rizoma/química , Esteroides/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Glicosídeos/química , Glicosídeos/isolamento & purificação , Humanos , Conformação Molecular , Simulação de Acoplamento Molecular , Esteroides/química , Esteroides/isolamento & purificação , Relação Estrutura-Atividade
18.
Phytochemistry ; 164: 206-214, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31177053

RESUMO

Eight undescribed cholestane glycosides named osaundersioside A-H, along with three previously known compounds named osaundersioside I-K were isolated from Ornithogalum saundersiae Baker bulbs (Asparagaceae). Their structures were elucidated by extensive spectroscopic analysis and chemical methods. All isolates were evaluated for their cytotoxic activity and inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production. Osaundersioside C was thus determined to exhibit specific cytotoxicity towards MCF-7 cell line with an IC50 value of 0.20 µM, Osaundersioside H exhibited inhibitory effect on NO production in macrophages at the concentration of 10-5 M, with inhibition rate of 56.81%.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Asparagaceae/química , Colestanos/farmacologia , Glicosídeos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Colestanos/química , Colestanos/isolamento & purificação , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Glicosídeos/química , Glicosídeos/isolamento & purificação , Humanos , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Células MCF-7 , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Casca de Planta/química , Raízes de Plantas/química , Relação Estrutura-Atividade
19.
BMC Complement Altern Med ; 19(1): 112, 2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31151442

RESUMO

BACKGROUND: The plant Holarrhena floribunda (H. floribunda; G. Don) is indigenous to sub-Saharan Africa and is traditionally used to treat several ailments. The present study was carried out to isolate and characterize bioactive compounds with anti-proliferative activity present in H. floribunda extracts. METHODS: Compounds were isolated from H. floribunda using the bioassay-guided fractionation technique of repeated column chromatography and the step-wise application of the MTT reduction assay to assess antiproliferative bioactivity. The structures of the compounds were identified mainly using NMR. The effects of the isolated compounds on the viability, cell cycle and proliferation of human cancer cell lines (MCF-7, HeLa and HT-29) as well as the non-cancerous human fibroblast cell line (KMST-6) were investigated. RESULTS: Bioassay-guided fractionation yielded two steroidal alkaloids: holamine (1) and funtumine (2). The MTT reduction assay shows that both compounds exhibited selective dose-dependent cytotoxicity against the cancer cell lines studied. The isolated compounds induced cell cycle arrest at the G0/G1 and G2/M phases in the cancer cell lines with significant reduction in DNA synthesis. The results obtained show that the cancer cells (MCF-7, HeLa and HT-29) used in this study were more sensitive to the isolated compounds compared to the noncancerous fibroblast cells (KMST-6). CONCLUSION: The ability of the isolated compounds to cause cell cycle arrest and reduce DNA synthesis raises hopes for their possible development and use as potent anticancer drugs. However, more mechanistic studies need to be done for complete validation of the efficacy of the two compounds.


Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Ciclo Celular/efeitos dos fármacos , Holarrhena/química , Fitosteróis/isolamento & purificação , Linhagem Celular Tumoral , Replicação do DNA/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Fitosteróis/farmacologia
20.
J Agric Food Chem ; 67(26): 7274-7280, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31244200

RESUMO

Bioactivity-guided separation led to the isolation of six novel phenanthrenes, spiranthesphenanthrenes A-F (1-6), together with 19 known compounds, including seven phenanthrenes (7-13), one bibenzyl compound (14), five flavonoids (15-16 and 20-22), and six simple phenolic compounds (17-19 and 23-25), from the petroleum ether (PE) and ethyl acetate (EtOAc) extracts of Spiranthes sinensis (Pers.) Ames, an edible medicinal plant named "panlongshen" in Chinese that is popularly used in medicinal foods and herbal teas. The structures of the obtained compounds were identified on the basis of extensive NMR spectroscopy and HR-ESI-MS analyses. The cytotoxicities of the phenanthrenes (1-13), the bibenzyl compound (14) , and the flavonoids (15-16 and 20-22) toward SGC-7901, HepG2, and B16-F10 cell lines were examined in vitro. Compounds 1 and 7 exhibited moderate cytotoxic activities toward all of the selected cancer cell lines, and their IC50 values ranged from 19.0 ± 7.3 to 30.2 ± 5.6 µM. Spiranthesphenanthrene A (1) exhibited higher cytotoxic activity than the positive control cisplatin toward the B16-F10 cell line (IC50 = 19.0 ± 7.3 µM). A wound healing assay revealed the inhibition of the migration of B16-F10 cancer cells in a time- and dose-dependent pattern by treatment with 2.5, 5, and 10 µM solutions of compound 1 for 24 and 48 h, respectively. Western blots revealed that compound 1 obviously increased the level of the E-cadherin protein (an epithelial marker) and decreased the levels of the vimentin and N-cadherin proteins (mesenchymal markers). Furthermore, the level of the transcription factor Snail was also obviously decreased by compound 1 in a dose-dependent manner. Taken together, compound 1 inhibits the migration of B16-F10 cancer cells, which may be closely related to the inhibition of the epithelial-mesenchymal transition. Compound 1 represents a promising drug candidate for the prevention of tumor metastasis.


Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Orchidaceae/química , Fenantrenos/química , Fenantrenos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Fenantrenos/isolamento & purificação , Extratos Vegetais/isolamento & purificação
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