RESUMO
Guaianolide dimers represent a unique class of natural products with anticancer activities, but their low content in plants has limited in-depth pharmacological studies. Lavandiolide I is a guaianolide dimer isolated from Artemisia species, and had been synthesized on a ten-gram scale in four steps with 60 % overall yield, which showed potent antihepatoma activity on the HepG2, Huh7, and SK-Hep-1 cell lines with IC50 values of 12.1, 18.4, and 17.6 µM, respectively. To explore more active dimers, 33 lavandiolide I derivatives were designed, synthesized, and evaluated for their inhibitory activity on human hepatoma cell lines. Among them, 10 derivatives were more active than lavandiolide I and sorafenib on the three cell lines. The primary structure-activity relationship concluded that the introduction of aldehyde, ester, azide, amide, carbamate and urea functional groups at C-14' of the guaianolide dimer significantly enhanced the antihepatoma activity. Among these compounds, derivatives 25, 27, and 33 enhanced antihepatoma activity more than 1.2-5.8 folds than that of lavandiolide I, and demonstrated low toxicity to the human liver cell lines (THLE-2) and good safety profiles with selective index ranging from 1.3 to 3.4, while lavandiolide I was more toxic to THLE-2 cells. This work provides new insights into enhancing the antihepatoma efficacy and reducing the toxicity of sesquiterpenoid dimers.
Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Sesquiterpenos de Guaiano , Humanos , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Proliferação de Células , Neoplasias Hepáticas/tratamento farmacológico , Estrutura Molecular , Relação Estrutura-Atividade , Linhagem Celular Tumoral , Sesquiterpenos de Guaiano/síntese química , Sesquiterpenos de Guaiano/química , Sesquiterpenos de Guaiano/farmacologiaRESUMO
Three uncommon isospongian diterpenoids including a new one, 3-epi-kravanhin A (2), were isolated from the leaves of Amomum tsao-ko. Compounds 2 and 3 dose-dependently promoted GLP-1 secretion on STC-1 cells with promotion ratios of 109.7% and 186.1% (60 µM). Mechanism study demonstrated that the GLP-1 stimulative effects of 2 and 3 were closely related with Ca2+/CaMKII and PKA pathways, but irrelevant to GPBAR1 and GPR119 receptors. Moreover, compound 1 showed moderate DPP-4 inhibitory activity with an IC50 value of 311.0 µM. Molecular docking verified the binding affinity of 1 with DPP-4 by hydrogen bonds between the γ-lactone carbonyl (C-15) and Arg61 residue. Bioinformatics study indicated that compound 1 exerted antidiabetic effects by improving inflammation, oxidative stress and insulin resistance. This study first disclosed the presence of isospongian diterpenoids in A. tsao-ko, which showed antidiabetic potency by promoting GLP-1 secretion and inhibiting DPP-4 activity.
RESUMO
Glucagon-like peptide-1 (GLP-1) secretagogues are fascinating pharmacotherapies to overcome the defects of GLP-1 analogs and dipeptidyl peptidase-4 (DPP-4) inhibitors in treating diabetes and obesity. To discover new GLP-1 secretagogues from natural sources, alpigalangols A-Q (1-17), 17 new labdane diterpenoids including four unusual nor-labdane and N-containing ones, were isolated from the fruits of Alpinia galanga. Most of the isolates showed GLP-1 promotive effects in NCl-H716 cells, of which compounds 3, 4, 12, and 14-17 were revealed with high promoting rates of 246.0%-413.8% at 50 µM. A mechanistic study manifested that the most effective compound 12 upregulated the mRNA expression of Gcg and Pcsk1, and the protein phosphorylation of PKA, CREB, and GSK3ß, but was inactive on GPBAR and GPR119 receptors. Network pharmacology analysis indicated that the PI3K-Akt pathway was involved in the GLP-1 stimulation of 12, which was highly associated with AKT1, CASP3, PPARG, and ICAM1 proteins. This study suggests that A. galanga is rich in diverse labdane diterpenoids with GLP-1 promoting effects, representing a new type of antidiabetic candidates from natural sources.
RESUMO
Artemisia annua, also known as "Qinghao" in Chinese, is a famous traditional Chinese medicine and has been used for the treatment of malaria and various tumors. In this study, three novel sesquiterpenoid-flavonol hybrids, artemannuols A-C (1-3), were isolated and elucidated by extensive spectral data and ECD calculations. Structurally, artemannuols A-C (1-3) are the first examples of sesquiterpenoid-flavonol hybrids fused by an ether bond, among which artemannuols A and B (1 and 2) are composed of bisabolane-type sesquiterpenoid and flavonol moieties, and artemannuol C (3) is composed of humulane-type sesquiterpenoid and flavonol moieties. The antihepatoma assay suggested that compounds 1-3 showed inhibitory effects against HepG2, Huh7, and SK-Hep-1 cell lines with IC50 values in the range of 32.7 to 70.4 µM.
Assuntos
Artemisia annua , Sesquiterpenos , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Linhagem CelularRESUMO
Artemyrianolide H (AH) is a germacrene-type sesquiterpenolid isolated from Artemisia myriantha, and showed potent cytotoxicity against three human hepatocellular carcinoma cell lines HepG2, Huh7, and SK-Hep-1 with IC50 values of 10.9, 7.2, and 11.9 µM, respectively. To reveal structure-activity relationship, 51 artemyrianolide H derivatives including 19 dimeric analogs were designed, synthesized, and assayed for their cytotoxicity against three human hepatoma cell lines. Among them, 34 compounds were more active than artemyrianolide H and sorafenib on the three cell lines. Especially, compound 25 exhibited the most promising activity with IC50 values of 0.7 (HepG2), 0.6 (Huh7), and 1.3 µM (SK-Hep-1), which were 15.5, 12.0, and 9.2-fold higher than that of AH and 16.4, 16.3 and 17.5-fold higher than that of sorafenib. Cytotoxicity evaluation on normal human liver cell lines (THLE-2) demonstrated good safety profile of compound 25 with SI of 1.9 (HepG2), 2.2 (Huh 7) and 1.0 (SK-Hep1). Further studies revealed that compound 25 dose-dependently arrested cells at G2/M phase which was correlated with the up-regulation of both cyclin B1 and p-CDK1, and induced apoptosis through the activation of mitochondrial pathways in HepG2 cells. In addition, the migratory and invasive abilities in HepG2 cells after treatment with 1.5 µM of compound 25 were decreased by 89% and 86% with the increase of E-cadherin expression accompanied by the decrease of N-cadherin, vimentin expression. Bioinformatics analysis based on machine learning predicted that PDGFRA and MAP2K2 might be acting targets of compound 25, and SPR assays demonstrated compound 25 were bound with PDGFRA and MAP2K2 with KD value of 0.168 nM, and 8.49 µM, respectively. This investigation proposed that compound 25 might be considered as a promising lead compound for the development of antihepatoma candidate.
Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Sorafenibe/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/patologia , Relação Estrutura-Atividade , Células Hep G2 , Proliferação de Células , Apoptose , Ensaios de Seleção de Medicamentos Antitumorais , Linhagem Celular TumoralRESUMO
Inspired by our previous finding that disesquiterpenoids showed more potent antihepatoma cytotoxicity than their corresponding parent monomers, natural product-like guaianolide-germacranolide heterodimers were designed and synthesized from guaianolide diene and germacranolides via a biomimetic Diels-Alder reaction to provide three antihepatoma active dimers with novel scaffolds. To explore the structure-activity relationship, 31 derivatives containing ester, carbamate, ether, urea, amide, and triazole functional groups at C-14' were synthesized and evaluated for their cytotoxic activities against HepG2, Huh7, and SK-Hep-1 cell lines. Among them, 25 compounds were more potent than sorafenib against HepG2 cells, 15 compounds were stronger than sorafenib against Huh7 cells, and 17 compounds were stronger than sorafenib against SK-Hep-1 cells. Compound 23 showed the most potent cytotoxicity against three hepatoma cell lines with IC50 values of 4.4 µM (HepG2), 3.7 µM (Huh7), and 3.1 µM (SK-Hep-1), which were 2.7-, 2.2-, and 2.8-fold more potent than sorafenib, respectively. The underlying mechanism study demonstrated that compound 23 could induce cell apoptosis, prevent cell migration and invasion, cause G2/M phase arrest in SK-Hep-1 cells. Network pharmacology analyses predicted PDGFRA was one of the potential targets of compound 23, and surface plasmon resonance (SPR) assay verified that 23 had strong affinity with PDGFRA with a dissociatin constant (KD) value of 90.2 nM. These promising findings revealed that structurally novel guaianolide-germacranolide heterodimers might provide a new inspiration for the discovery of antihepatoma agents.
Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Antineoplásicos/uso terapêutico , Relação Estrutura-Atividade , Células Hep G2 , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular , ApoptoseRESUMO
Our previous study demonstrated that guaiane-type sesquiterpenoid ludartin showed potent antihepatoma activity against two human hepatocellular carcinoma cell lines, HepG2 and Huh7, with IC50 values of 32.7 and 34.3 µM, respectively. In this study, 34 ludartin derivatives were designed, synthesized and evaluated for their cytotoxic activities against HepG2 and Huh7 cell lines using an MTT assay in vitro. As a result, 17 compounds increased the activity against HepG2 cells, and 20 compounds enhanced the activity against Huh7 cells; 14 derivatives 2, 4-7, 9, 11, 17, 24, 28-30 and 32-33 were superior to ludartin on both HepG2 and Huh7 cells. In particular, dimeric derivative 33 as the most active compound showed 20-fold and 17-fold enhancement of cytotoxicity against HepG2 and Huh7 cells compared to that of ludartin. These results suggested that compound 33 could serve as a promising lead compound against liver cancer. Graphical abstract.
RESUMO
Random screening revealed that the EtOH extract of Artemisia atrovirens showed significant cytotoxicity against two human hepatoma cell lines (HepG2 and Huh7) with the inhibitory ratio of 98.9% and 99.7% at the concentration of 100 µg/mL. Further bioactivity-guided isolation of active fraction led to 16 new guaiane-type sesquiterpenoids, artematrovirenins A-P (1-16). Their structures were elucidated by extensive spectroscopic data. The absolute stereochemistry of compounds 1 and 14 was determined by single-crystal X-ray diffraction analyses. Pharmacological evaluation suggested that five compounds (3, 5, 8, 10, and 15) exhibited cytotoxicity, compounds 3 and 5 displayed cytotoxicity against HepG2 cell line with an IC50 values of 8.0 and 16.0 µM, as well as against Huh7 cell line with values of 18.2 and 32.2 µM.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Artemisia/química , Sesquiterpenos de Guaiano/farmacologia , Sesquiterpenos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Teoria da Densidade Funcional , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos de Guaiano/química , Sesquiterpenos de Guaiano/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
Artatrovirenols A and B (1 and 2), two novel cagelike sesquiterpenoids, possess a unique 5/5/6/5/5-pentacyclic and a 5/5/6/5-tetracyclic system with an unprecedented tetracyclo[5.3.1.1.4,1101,5]dodecane scaffold from Artemisia atrovirens. The structures of compounds 1 and 2 including their absolute stereochemistry were elucidated through extensive spectroscopic analyses, X-ray crystallography, and quantum chemical calculations. Plausible biosynthetic pathways for the new isolates were proposed from the naturally occurring arglabin (3) via the key intramolecular Diels-Alder cycloaddition. Compound 1 showed cytotoxicity against three human hepatoma cell lines (HepG2, SMMC-7721, and Huh7) with half maximal inhibitory concentration values of 123.8, 44.0, and 142.6 µΜ, respectively.
Assuntos
Artemisia , Sesquiterpenos , Linhagem Celular , Cristalografia por Raios X , Humanos , Sesquiterpenos/farmacologiaRESUMO
Spiroseoflosterol (1), a 7(8â9)-abeo-ergostane steroid with a unique spiro[4.5]decan-6-one system, was isolated from the fruiting bodies of Butyriboletus roseoflavus. Its structure was determined by interpretation of comprehensive spectroscopic, X-ray, and computational data. A plausible biogenetic pathway for spiroseoflosterol (1) was postulated based on a key semipinacol rearrangement. Compound 1 was cytotoxic to HepG2 and Huh7/S (sorafenib-resistant Huh7) with IC50 values of 9.1 and 6.2 µM, respectively.
Assuntos
Antineoplásicos/farmacologia , Basidiomycota/química , Carpóforos/química , Triterpenos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Ascomicetos/química , Ergosterol/análogos & derivados , Humanos , Estrutura Molecular , Esteroides/química , Triterpenos/química , Triterpenos/isolamento & purificaçãoRESUMO
Random screening suggested that the EtOH extract of Artemisia myriantha (Asteraceae) and its EtOAc fraction had cytotoxicity against HepG2 cells with inhibitory ratios of 30.6% and 53.5% at 50.0 µg/mL. Bioassay-guided isolation of the most active fractions (Fr. C and Fr. D) afforded 19 new sesquiterpenolides, artemyrianolides A-S (1-19), involving 13 germacranolides (1-13), four guaianolides (14-17), and two eudesmanolides (18 and 19), together with 16 known sesquiterpenoids (20-35). The new compounds were characterized by physical data analyses (HRESIMS, IR, 1D and 2D NMR, ECD), and the absolute configurations of compounds 1, 2, and 11 were determined by X-ray crystallography. Structurally, compounds 2 and 11-13 maintain an uncommon cis-fused 10/5 bicyclic system and compound 12 possesses an unusual (7S) configuration. Twenty of the compounds exhibited cytotoxicity against HepG2, Huh7, and SMMC-7721 cell lines. Compound 9 showed cytotoxic activity on both HepG2 and Huh7 cells with IC50 values of 8.6 and 8.8 µM, and compounds 8 and 33 showed cytotoxicity to the three human hepatoma cell lines with IC50 values of 4.9 and 7.4 µM (HepG2), 4.3 and 7.8 µM (Huh7), and 3.1 and 9.8 µM (SMMC-7721), respectively.
Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Artemisia/química , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Células Hep G2 , Humanos , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Estrutura Molecular , Espectrometria de Massas por Ionização por Electrospray , Difração de Raios XRESUMO
Gastrodia elata is a famous traditional Chinese herb with medicinal and edible application. In this study, nine polybenzyls (1-9), including six new ones (2-5, 7 and 9), were isolated from the EtOAc extract of G. elata. Five compounds 1, 3, 4, 6 and 8 were found to activate melatonin receptors. Especially, compound 1 showed agonistic effects on MT1 and MT2 receptors with EC50 values of 237 and 244⯵M. For better understanding their structure-activity relationships (SARs), ten polybenzyl analogs were further synthesized and assayed for their activities on melatonin receptors. Preliminary SARs study suggested that two para-hydroxy groups were the key pharmacophore for maintaining activity. Molecular docking simulations verified that compound 1 could strongly interact with MT2 receptor by bonding to Phe 118, Gly 121, His 208, Try 294 and Ala 297 residues.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Gastrodia/química , Extratos Vegetais/farmacologia , Receptores de Melatonina/agonistas , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Células HEK293 , Humanos , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
Uncaria rhynchophylla (Gou-Teng) as the monarch herb of many formulae (Fufang), e.g. "Tian-Ma-Gou-Teng-Yin," "Ling-Jiao-Gou-Teng-Yin," and "Yi-Gan-San", is a famous traditional Chinese medicine documented in the Chinese pharmacopoeia for mental and cardiovascular diseases. In the traditional Chinese medicine system, only the hook-bearing stems are used as the crude materials for Gou-Teng, and the hooks are always considered more effective than the stems. Focusing on the mono-herb and its active constituents from combinatorial formulae is the core idea of reductionism of traditional Chinese medicine theory. Detailed liquid chromatography with mass spectrometry analysis on the hooks of U. rhynchophylla was performed to profile the chemical constituents based on tandem mass spectrometry fragmentation and UV absorption. Under the guidance of liquid chromatography with ion trap/time-of-flight mass spectrometry, one new indole alkaloid triglycoside (1), together with five known compounds 2-6 as the main constituents, were isolated from the hooks of U. rhynchophylla by various column chromatography methods. Compound 1 showed moderate activity on MT1 and MT2 melatonin receptors with agonistic rates of 79.6 and 46.3% at the concentration of 1 mM. This dereplication strategy can be equally applicable to rapidly disclose the active constituents of other Chinese herbs through targeted purification.
Assuntos
Glicosídeos/isolamento & purificação , Alcaloides Indólicos/isolamento & purificação , Estruturas Vegetais/química , Uncaria/química , Cromatografia Líquida , Glicosídeos/química , Alcaloides Indólicos/química , Espectrometria de Massas , Fatores de TempoRESUMO
(±)-Uncarilins A and B (1a/1b and 2a/2b), two pairs of unusual dimeric isoechinulin-type enantiomers with a symmetric four-membered core, were isolated from Uncaria rhynchophylla driven by LCMS-IT-TOF analyses. Their structures were elucidated by extensive 1D and 2D NMR spectra, X-ray diffraction, and ECD spectroscopic data. (-)-Uncarilin B (2a) showed activities on MT1 and MT2 receptors with agonistic rates of 11.26% and 52.44% at a concentration of 0.25 mM.
Assuntos
Medicamentos de Ervas Chinesas/isolamento & purificação , Alcaloides Indólicos/isolamento & purificação , Uncaria/química , Medicamentos de Ervas Chinesas/química , Humanos , Alcaloides Indólicos/química , Indóis , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Receptor MT1 de Melatonina/agonistas , Receptor MT2 de Melatonina/agonistas , EstereoisomerismoRESUMO
Uncaria rhynchophylla (Gou-Teng in Chinese) is officially documented in Chinese pharmacopoeia as one of the authentic sources for the crude drug of Gou-Teng which has long been used for mental and cardiovascular diseases. Indole alkaloids are the characteristic constituents responsible for the desired hypotensive effect; however, the psychiatric active constituents of Gou-Teng are still unclear. According to traditional Chinese medicine theory, only the hook-bearing stems of U. rhynchophylla are used as the crude materials for Gou-Teng, while its leaves and fruits are scarcely used. The present study aimed to compare the metabolic fingerprints of different parts (hooks, stems, leaves and fruits) of U. rhynchophylla by LC-DAD-MS/MS analysis and further evaluate their psychiatric activities on HEK293 cell line in vitro. A total of 38 constituents including 26 alkaloids, six flavonoids, two triterpenoids, two chlorogenic acid analogs and two other compounds were characterized. The different parts of U. rhynchophylla can be well differentiated from their chemical profiles. Leaves displayed the most potent activity on both MT1 and MT2 receptors, with agonistic rates of 39.7% and 97.6%. For 5-HT1A and 5-HT2C receptors, hooks showed the strongest activity with agonistic rates of 92.6% and 83.1%, respectively. This investigation provided valuable information for understanding the chemical divergence between different parts of U. rhynchophylla, and their substantial bases for psychiatric purposes.
Assuntos
Sobrevivência Celular/efeitos dos fármacos , Alcaloides Indólicos/administração & dosagem , Alcaloides Indólicos/química , Extratos Vegetais/química , Folhas de Planta/química , Uncaria/química , Células HEK293 , Humanos , Espectrometria de Massas/métodos , Fitoterapia/métodos , Extratos Vegetais/administração & dosagem , Psicotrópicos/administração & dosagem , Psicotrópicos/químicaRESUMO
Twenty-four gramine derivatives were synthesized and evaluated on MT1 and 5-HT1A receptors in vitro. Among them, seven derivatives (7, 8, 16, 19, 20, 21, and 24) exhibited higher agonisting activities on MT1 or 5-HT1A receptors. Compared with gramine, derivatives 7, 8, 16, 19, 20, 21, and 24 displayed 1.6-3.5-fold increase in agonistic rates on 5-HT1A receptor. Particularly, derivatives 7, 19, and 21 exhibited significant agonistic activities on MT1 and 5-HT1A receptors with EC50 values of 0.51, 0.39, 0.50 mΜ and 0.28, 0.46, 0.23 mΜ, respectively. The preliminary structure-activity relationships of gramine derivatives were summarized for further investigation on MT1 and 5-HT1A receptors as new potential agonists.
Assuntos
Alcaloides/síntese química , Alcaloides/farmacologia , Agonistas do Receptor 5-HT1 de Serotonina/síntese química , Agonistas do Receptor 5-HT1 de Serotonina/farmacologia , Alcaloides/química , Animais , Alcaloides Indólicos , Estrutura Molecular , Agonistas do Receptor 5-HT1 de Serotonina/química , Relação Estrutura-AtividadeRESUMO
Two new secoiridoids, swerpatic acid (1) with an unusual C8 skeleton and swerpalactone (2), were isolated along with ten known compounds (3-12) from the whole plants of Swertia patens. Their structures were elucidated by comprehensive spectroscopic analyses. Eight compounds were evaluated for their anti-hepatitis B virus (HBV) activities on Hep G 2.2.15 cell line in vitro. Compounds 4 and 10 showed moderate inhibitory activities on the secretion of HBsAg with IC50 values of 1.96 and 0.50 mM.
Assuntos
Antivirais/isolamento & purificação , Antivirais/farmacologia , Vírus da Hepatite B/efeitos dos fármacos , Iridoides/isolamento & purificação , Iridoides/farmacologia , Swertia/química , Antivirais/química , Células Hep G2 , Antígenos de Superfície da Hepatite B , Humanos , Concentração Inibidora 50 , Iridoides/química , Estrutura MolecularRESUMO
In this paper, the chemical constituents and bioactivities of leaves of Nicotiana tabacum were investigated. Six compounds were isolated by means of various chromatographic techniques (silica gel, Sephadex LH-20, MCI GEL CHP-20P and HPLC), and their structures were elucidated as cis-5'-(2-oxopropyl)-nicotine (1), 3-O-(9, 12, 15-octadecatrienoyl)-glyceryl-ß-D-galactppyranoside (2), (l'R, 2R, 5S, 10R)-2-(1', 2'-dihydroxy-l'-methylethyl)-6, 10-dimethylspiro [4, 5] dec-6-en-8-one (3), (l'S, 2R, 5S, l0R)-2-(1', 2'-dihydroxy-l'-methylethyl)-6, 10-dimethylspiro [4, 5] dec-6-en-8-one (4),2, 3-dihydroxypropyl-ß-D-galactoside (5) and phenylethyl ß-D-glucopyranoside (6) by extensive spectroscopic analyses (UV, IR, MS, 1D- and 2D-NMR). Among them, compound 1 is a new alkaloid, and compounds 2-6 are isolated for the first time from N. tabacum. Compounds 1 and 2 were assayed for agitating activities on transient receptor potential vanilloid 1 (TRPV1), melatonin receptor 1 and 2 (MT1 and MT2), 1 showed agitating rate of 55.41% (1.53mmolâ¢L⻹) on MT2 and 2 possessed agitating rate of 128.11% (0.59 mmolâ¢L⻹) and 52.00% (0.73mmolâ¢L⻹) on TRPV1 and MT1, respectively.
Assuntos
Alcaloides/química , Alcaloides/farmacologia , Nicotiana/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Alcaloides/isolamento & purificação , Animais , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , EstereoisomerismoRESUMO
Thirteen compounds were isolated from the ethyl acetate extract of the rhizomes of Cyperus rotundus(Xiangfu) by means of various chromatographic techniques(silica gel, Al2O3, Sephadex LH-20, MCI GEL CHP-20P and HPLC), and their structures were identified as cyperotundic acid(1),(4S, 5E, 10R)-7-oxo-trinoreudesm-5-en-4ß-ol(2), 4-hydroxy-4, 7-dimethyl-1-tetralone(3), taraxerone(4), dammaradienyl acetate(5), zeorin(6), sarmentine(7), guineensine(8), pellitorine(9), caprolactam(10), liriodendrin(11), 3-hydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-2-[4-(3-hydroxy-1-(E)-propenyl)-2,6-dimethoxyphenoxy]propyl-ß-D-glucopyranoside(12)and 1-(3, 4-methylenedioxyphenyl)-1E-tetradecene(13) by extensive spectroscopic analyses(IR, MS, 1D-and 2D-NMR). Compound 1 was a new rearranged sesquiterpene and named as cyperotundic acid, which did not obey the isoprene rule.Compounds 2-13 were obtained from the genus Cyperus for the first time.
Assuntos
Cyperus/química , Medicamentos de Ervas Chinesas/química , Sesquiterpenos/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Rizoma/química , Sesquiterpenos/isolamento & purificaçãoRESUMO
Twenty-four derivatives of erythrocentaurin (ET) were synthesized and evaluated for their anti-HBV activities on HepG 2.2.15 cell line in vitro. Eight compounds 1, 2, 5, 8, 9, 1e, 1k, and 1m increased activity against HBV DNA replication with the SI values higher than 11. In particular, derivatives 1e and 1k exhibited the most potent inhibition on HBV DNA replication with the IC50 values of 0.026 mM (SI>70.8) and 0.045 mM (SI>36.0), respectively. The primary structure-activity relationships (SARs) of ET derivatives were summarized for exploring potent anti-HBV agents.