RESUMO
A highly sensitive micelle-induced sensory has been developed for detection of long-chain aldehydes as potential biomarkers of respiratory cancers. The micelle-like sensor was fabricated through the partial self-assembly of CTAB and S2 surfactants, containing a fluorescent hydrazine-functionalized dye (Naph-NH2). In principle, long-chain aldehydes with amphiphilic character act as the induced-fit surfactants to form well-entrapped micellar particles, as well as react with Naph-NH2 to form hydrazone derivatives resulting in fluorescent enhancement. The limit of detection (LOD) of micellar Naph-NH2/CTAB/S2 platform was calculated to be â¼ 64.09-80.98 µM for detection of long-chain aldehydes, which showed fluorescent imaging in lung cancer cells (A549). This micellar sensory probe demonstrated practical applicability for long-chain aldehyde sensing in human blood samples with an accepted percent recovery of ~ 94.02-102.4%. Beyond Naph-NH2/CTAB/S2 sensor, the milcellar hybrid sensor was successfully developed by incorporating a micelle-like platform with supramolecular gel regarding to carboxylate-based gelators (Gel1), which showed a tenfold improvement in sensitivity. Expectedly, the determination of long-chain aldehydes through these sensing platforms holds significant promise for point-of-care cancer diagnosis and therapy.
Assuntos
Aldeídos , Corantes Fluorescentes , Hidrogéis , Limite de Detecção , Micelas , Humanos , Aldeídos/química , Corantes Fluorescentes/química , Hidrogéis/química , Células A549 , Hidrazinas/química , Cetrimônio/química , Tensoativos/químicaRESUMO
Four flavonoid glycosides, namely quercetin-3-O-rhamnoside (1), kaempferol-3-O-ß-D-glucopyranosyl (2), kaempferol-7-O-α-L-rhamnopyranoside (3), and kaempferol-3-O-ß-D-glucopyranosyl-7-O-α-L-rhamnopyranoside (4), from Nephelium lappaceum L. seeds were evaluated for their efficacy against melanin inhibition in B16F10 melanoma cells and tyrosinase inhibition. Among them, kaempferol-7-O-α-L-rhamnopyranoside (3) displayed the highest potency in both activities without any significant cytotoxicity. The combination of compound 3 and arbutin in specific proportions demonstrated a synergistic effect (CI < 1) in inhibiting melanin production in B16F10 cells and tyrosinase inhibition. Additionally, a cosmetic formulation containing compound 3 and arbutin as active ingredients exhibited favorable stability under accelerated storage conditions. Quantitative analysis indicated that compound 3 and arbutin levels in the formulation were above 90% after one month of storage. Determination of the formulation's shelf life using the Q10 method, estimating it to be around 5.2 months from the date of manufacture. The synergy between arbutin and kaempferol-7-O-α-L-rhamnopyranoside (3) extracted from N. lappaceum substantially enhances both the whitening effectiveness and the stability of cosmetic formulations.
Assuntos
Arbutina , Quempferóis , Quempferóis/farmacologia , Arbutina/farmacologia , Monofenol Mono-Oxigenase , Melaninas , Estrutura Molecular , Glicosídeos/farmacologia , Flavonoides/farmacologiaRESUMO
Liver cancer refers primarily to hepatocellular carcinoma (HCC) accounting for over 90% of cases and is the highest incidence in men in Thailand. Over the past decades, the incidence of HCC dramatically increased with a strong rise of mortality rates. Garcinia mangostana, "Queen of Fruit" of Thailand, is known as a rich source of xanthones with potent cytotoxic properties against various cancer cells. Study on xanthones is provoking not only due to the structural diversity but also a wide variety of pharmacological activities. Hence the aim of the current study is to determine the effects of metabolites from G. mangostana root on cell proliferation and migration of hepatocellular carcinoma cells. Twenty-two metabolites, including two new benzophenones and one new biphenyl, were isolated and characterized. Five xanthones with a prenyl moiety showed significant cytotoxicity against both HCC cells tested; however, only dulxanthone D displayed the most promising activity on the migration of Huh7 HCC cells, comparable to sorafenib, a standard drug. Moreover, the compound dose-dependently induced apoptosis in Huh7 cells via mitochondrial pathway. Accordingly, dulxanthone D held a great potential for development as a novel migration inhibitor for effective HCC treatment.
Assuntos
Antineoplásicos Fitogênicos , Carcinoma Hepatocelular , Garcinia mangostana , Neoplasias Hepáticas , Xantonas , Antineoplásicos Fitogênicos/química , Benzofenonas/química , Compostos de Bifenilo , Carcinoma Hepatocelular/tratamento farmacológico , Frutas/química , Garcinia mangostana/química , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Extratos Vegetais/farmacologia , Xantonas/química , Xantonas/farmacologiaRESUMO
Two new xanthones, 1,3,6,7-tetrahydroxy-5-methoxy-4-(1',1'-dimethyl-2'-propenyl)-8-(3â³,3â³-dimethyl-2â³-propenyl)-xanthone (1) and (2'S)-7-hydroxy caloxanthone B (2), were isolated from the root of Thai Calophyllum inophyllum Linn., together with twelve known xanthones (3-14). The structures of new compounds were elucidated based on spectroscopic data. In addition, compounds 4, 6 and 8 were isolated from the genus Calophyllum for the first time. The isolated compounds were evaluated for their cytotoxic activity against colon HCT-116 and liver Hep-G2 cancer cells. Among tested compounds, xanthones 5 and 14 possessing a prenyl moiety and a pyranyl ring fused at C-2 and C-3 displayed the most potent and selective cytotoxicity against HCT-116 colon cancers with the same IC50 values of 3.04 µM.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Calophyllum/química , Xantonas/farmacologia , Linhagem Celular Tumoral , Neoplasias do Colo , Células Hep G2 , Humanos , Neoplasias Hepáticas , Estrutura Molecular , Compostos Fitoquímicos/farmacologia , Raízes de Plantas/química , Tailândia , Xantonas/químicaRESUMO
A new rearranged clerodane-type diterpene (1), tinobaenzigeride, and a new rearranged clerodane glucoside (2) were isolated from the stems of Tinospora baenzigeri, along with four known compounds (3â6). Their structures were elucidated by spectroscopic data analysis. In addition, the structure and configuration of 1 was confirmed by single-crystal X-ray diffraction analysis. Compound 1 are a rare example of rearranged clerodanes, since it contains a fully oxygenated tetrahydrofuran moiety. The isolated compounds were evaluated for their cytotoxicity against Hep-G2 and MCF-7 cancer cells, none of them did show any significant activity at 25 µM.
Assuntos
Diterpenos Clerodânicos/química , Tinospora/química , Humanos , Estrutura Molecular , TailândiaRESUMO
The rhytidenone family comprises spirobisnaphthalene natural products isolated from the mangrove endophytic fungus Rhytidhysteron rufulum AS21B. The biomimetic synthesis of rhytidenoneâ A was achieved by a Michael reaction/aldol/lactonization cascade in a single step from the proposed biosynthetic precursor rhytidenoneâ F. Moreover, the mode of action of the highly cytotoxic rhytidenoneâ F was investigated. The pulldown assay coupled with mass spectrometry analysis revealed the target protein PA28γ is covalently attached to rhytidenoneâ F at the Cys92 residue. The interactions of rhytidenoneâ F with PA28γ lead to the accumulation of p53, which is an essential tumor suppressor in humans. Consequently, the Fas-dependent signaling pathway is activated to initiate cellular apoptosis. These studies have identified the first small-molecule inhibitor targeting PA28γ, suggesting rhytidenoneâ F may serve as a promising natural product lead for future anticancer drug development.
Assuntos
Antineoplásicos/farmacologia , Materiais Biomiméticos/farmacologia , Naftalenos/farmacologia , Compostos de Espiro/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Ascomicetos/química , Materiais Biomiméticos/síntese química , Materiais Biomiméticos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Naftalenos/síntese química , Naftalenos/química , Compostos de Espiro/síntese química , Compostos de Espiro/químicaRESUMO
The plants in the genus Derris have proven to be a rich source of rotenoids, of which cytotoxic effect against cancer cells seem to be pronounced. However, their effect on angiogenesis playing a crucial role in both cancer growth and metastasis has been seldom investigated. This study aimed at investigating the effect of the eight rotenoids (1: -8: ) isolated from Derris trifoliata stems on three cancer cells and angiogenesis. Among them, 12a-hydroxyrotenone (2: ) exhibited potent inhibition on both cell growth and migration of HCT116 colon cancer cells. Further, anti-angiogenic assay in an ex vivo model was carried out to determine the effect of the isolated rotenoids on angiogenesis. Results revealed that 12a-hydroxyrotenone (2: ) displayed the most potent suppression of microvessel sprouting. The in vitro assay on human umbilical vein endothelial cells was performed to determine whether compound 2: elicits anti-angiogenic effect and its effect was found to occur via suppression of endothelial cells proliferation and tube formation, but not endothelial cells migration. This study provides the first evidence that compound 2: could potently inhibit HCT116 cancer migration and anti-angiogenic activity, demonstrating that 2: might be a potential agent or a lead compound for cancer therapy.
Assuntos
Inibidores da Angiogênese/farmacologia , Derris/química , Neovascularização Patológica/tratamento farmacológico , Rotenona/farmacologia , Inibidores da Angiogênese/síntese química , Inibidores da Angiogênese/isolamento & purificação , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células HCT116 , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Caules de Planta/química , Rotenona/química , Rotenona/isolamento & purificaçãoRESUMO
We investigated the tumor necrosis factor-alpha (TNF-α) inhibitory activity of sesquiterpenes from Saussurea lappa root extracts. According to the hexane and EtOAc extracts showing significant activity with IC50 values of 0.5 and 1.0 µg/mL, respectively, chromatographic fractionation of the extracts was performed and led to the isolation of 10 sesquiterpenes (1: -10: ). Costunolide (1: ), a major compound, and dehydrocostus lactone (4: ) exhibited high efficiency in decreasing TNF-α levels, with IC50 values of 2.05 and 2.06 µM, respectively. In addition, sesquiterpene analogues were synthesized to establish their structure-activity relationship (SAR) profile. Among the semi-synthetic analogues, compounds 6A: and 16: showed the most potent activity with IC50 values of 1.84 and 1.97 µM, respectively. More importantly, compound 6A: showed less toxicity than costunolide and 16: . These results provided the first SAR profile of sesquiterpene lactones and indicated that the α-methylene-γ-lactone moiety plays a crucial role in TNF-α inhibition. Additionally, the epoxide derivative 6A: might represent a lead compound for further anti-TNF-α therapies, owing to its potent activity and reduced toxicity.
Assuntos
Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológico , Lactonas/farmacologia , Extratos Vegetais/farmacologia , Saussurea/química , Sesquiterpenos/farmacologia , Anti-Inflamatórios/química , Concentração Inibidora 50 , Lactonas/química , Lactonas/isolamento & purificação , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Raízes de Plantas/química , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Relação Estrutura-Atividade , Fator de Necrose Tumoral alfa/efeitos adversosRESUMO
The cultivation of the mangrove-derived fungus Rhytidhysteron rufulum AS21B in acidic condition changed its secondary metabolite profile. Investigation of the culture broth extract led to the isolation and identification of two new spirobisnaphthalenes (1 and 2) together with eleven known compounds (3-13) from the crude extract of the fungus grown under an acidic condition as well as six known compounds (4, 10, 14-17) were isolated from the crude extract of the fungus grown under a neutral condition. Their structures were elucidated on the basis of extensive spectroscopic data. The isolated compounds were evaluated for their cytotoxicity against two human cancer cell lines, Ramos lymphoma and drug resistant NSCLC H1975. Compounds 2 and 10 displayed the most promising anti-tumor activity against both cancer cell lines.
Assuntos
Antineoplásicos/farmacologia , Ascomicetos/química , Naftalenos/farmacologia , Compostos de Espiro/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Ascomicetos/crescimento & desenvolvimento , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Conformação Molecular , Naftalenos/síntese química , Naftalenos/química , Compostos de Espiro/síntese química , Compostos de Espiro/química , Relação Estrutura-AtividadeRESUMO
Six new chamigrane sesquiterpenes, merulinols AâF (1â6), and four known metabolites (7â10) were isolated from the culture of the basidiomycetous fungus XG8D, a mangrove-derived endophyte. Their structures were elucidated mainly by 1D and 2D NMR, while the structures of 1 and 2 were further confirmed by single-crystal X-ray diffraction analysis. The in vitro cytotoxicity of all compounds was evaluated against three human cancer cell lines, MCF-7, Hep-G2, and KATO-3. Compounds 3 and 4 selectively displayed cytotoxicity against KATO-3 cells with IC50 values of 35.0 and 25.3 µM, respectively.
Assuntos
Basidiomycota/química , Endófitos/química , Fungos/química , Rhizophoraceae/microbiologia , Sesquiterpenos/química , Linhagem Celular Tumoral , Cristalografia por Raios X/métodos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Células Hep G2 , Humanos , Células MCF-7 , Estrutura Molecular , Sesquiterpenos/farmacologia , Tailândia , Difração de Raios X/métodosRESUMO
Five highly oxygenated chromones, rhytidchromones A-E, were isolated from the culture broth of a mangrove-derived endophytic fungus, Rhytidhysteron rufulum, isolated from Thai Bruguiera gymnorrhiza. Their structures were determined by analysis of 1D and 2D NMR spectroscopic data. The structure of rhytidchromone A was further confirmed by single-crystal X-ray diffraction analysis. These compounds were evaluated for cytotoxicity against four cancer cell lines (MCF-7, Hep-G2, Kato-3 and CaSki). All compounds, except for rhytidchromone D, displayed cytotoxicity against Kato-3 cell lines with IC50 values ranging from 16.0 to 23.3µM, while rhytidchromones A and C were active against MCF-7 cells with IC50 values of 19.3 and 17.7µM, respectively.
Assuntos
Antineoplásicos/isolamento & purificação , Ascomicetos/química , Cromonas/isolamento & purificação , Rhizophoraceae/microbiologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Cromonas/química , Cromonas/farmacologia , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Células Hep G2 , Humanos , Células MCF-7 , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Oxigênio , TailândiaRESUMO
Sonneratia ovata Backer, Sonneratiaceae, is a widespread plant in mangrove forests in Vietnam, Cambodia, Thailand, Indonesia. Sonneratia ovata's chemical composition remains mostly unknown. Therefore, we now report on the structural elucidation of three new phenolics, sonnerphenolic A (1), sonnerphenolic B (2), and sonnerphenolic C (23), a new cerebroside, sonnercerebroside (3) together with nineteen known compounds, including nine lignans (5-13), two steroids (14, 15), two triterpenoids (16, 17), three gallic acid derivatives (18-20), two phenolic derivatives (4, 22) and a 1-O-benzyl-ß-d-glucopyranose (21) isolated from the leaves of Sonneratia ovata. Their chemical structures were established by spectroscopic data, as well as high resolution mass spectra and comparison with literature data. The in vitro acetylcholinesterase (AChE) inhibition and cytotoxic activities against HeLa (human epithelial carcinoma), NCI-H460 (human lung cancer), MCF-7 (human breast cancer) cancer cell lines and PHF (primary human fibroblast) cell were evaluated on some extracts and purified compounds at a concentration of 100 µg/mL. Compounds (5, 6, 23) exhibited cytotoxicity against the MCF-7 cell line with the IC50 values of 146.9±9.0, 114.5±7.2, and 112.8±9.4 µM, respectively, while they showed nontoxic with the normal cell (PHF) with IC50s >277 µM. Among 15 tested compounds, (S)-rhodolatouchol (22) showed inhibition against AChE with an IC50 value of 96.1±14.5 µM.
Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Plantas/química , Acetilcolinesterase/metabolismo , Linhagem Celular Tumoral , Humanos , Espectroscopia de Ressonância Magnética , Modelos MolecularesRESUMO
In this study, limonoids isolated from Xylocarpus plants were tested for their in vitro anti-inflammatory effects. The results demonstrated that only 7-deacetylgedunin (1), a gedunin-type limonoid, significantly inhibited lipopolysaccharide- and interferon-γ-stimulated production of nitric oxide in murine macrophage RAW 264.7 cells. The suppression of nitric oxide production by 1 was correlated with the downregulation of mRNA and protein expression of inducible nitric oxide synthase. Mechanistic studies revealed that the transcriptional activity of nuclear factor-κB, IκBα degradation, and the activation of mitogen-activated protein kinases, stimulated with lipopolysaccharide and interferon-γ, were suppressed by 1.
Assuntos
Anti-Inflamatórios/farmacologia , Mediadores da Inflamação/metabolismo , Limoninas/farmacologia , Meliaceae/química , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico/metabolismo , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/uso terapêutico , Regulação para Baixo , Proteínas I-kappa B/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interferon gama/metabolismo , Limoninas/uso terapêutico , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Inibidor de NF-kappaB alfa , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Fitoterapia , Extratos Vegetais/uso terapêutico , Células RAW 264.7 , RNA Mensageiro/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Seven new limonoids, namely, xylorumphiins E-J (1-2 and 4-7) and 2-hydroxyxylorumphiin F (3), along with three known derivatives (8-10), were isolated from the seeds of Xylocarpus rumphii. 2-Hydroxyxylorumphiin F (3) and xylorumphiin I (6) displayed moderate inhibitory activity against nitric oxide production from lipopolysaccharide-activated macrophages with IC50 values of 24.5 and 31.3 µM, respectively.
Assuntos
Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Limoninas/isolamento & purificação , Limoninas/farmacologia , Sementes/química , Anti-Inflamatórios/química , Concentração Inibidora 50 , Limoninas/química , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Estrutura Molecular , Óxido Nítrico/biossíntese , Ressonância Magnética Nuclear Biomolecular , TailândiaRESUMO
Rhytidenone A (1), a unique spirobisnaphthalene with a 1,7-dioxaspiro[4,4]nonan-2-one motif, and five new spirobisnaphthalenes, rhytidenones B-F (2-6), were isolated from the extract of a cultured fungal endophyte, Rhytidhysteron sp. AS21B. Their structures were elucidated mainly by analysis of NMR spectroscopic data. The structure and configuration of 1 were further confirmed by single-crystal X-ray diffraction analysis. Compounds 3 and 4 exhibited significant inhibitory activity against nitric oxide production from activated macrophages with IC50 values of 0.31 and 3.60 µM, respectively.
Assuntos
Ascomicetos/química , Naftalenos/isolamento & purificação , Compostos de Espiro/isolamento & purificação , Animais , Cristalografia por Raios X , Feminino , Indometacina/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos , Conformação Molecular , Estrutura Molecular , Naftalenos/química , Naftalenos/farmacologia , Ressonância Magnética Nuclear Biomolecular , Folhas de Planta/microbiologia , Salvadoraceae/microbiologia , Compostos de Espiro/química , Compostos de Espiro/farmacologia , TailândiaRESUMO
Three new spirobisnaphthalenes (1-3) were isolated from the mangrove-derived fungus Rhytidhysteron sp., together with five known derivatives (4-8). The structures of the compounds were established on the basis of extensive spectroscopic data, and the relative configurations of their stereogenic carbons were determined by a single-crystal X-ray crystallographic analysis. Compounds 3-5 displayed cytotoxicity against both cancer cell lines, MCF-7 and CaSki, while 2 was active only on CaSKi cells.
Assuntos
Ascomicetos/química , Naftalenos/metabolismo , Naftalenos/farmacologia , Rhizophoraceae/microbiologia , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/isolamento & purificação , Antibióticos Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Fermentação , Humanos , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Micélio/química , Naftalenos/isolamento & purificação , Espectrofotometria Ultravioleta , Difração de Raios XRESUMO
Two new rearranged limonoids, harperforatin (1) and harperfolide (2), and a new chromone, harperamone (3), were isolated from fruits and roots of Harrisonia perforata, together with eight known compounds. Their structures were elucidated on the basis of spectroscopic data. Harperfolide (2) exhibited potent anti-inflammatory activity by suppressing nitric oxide (NO) production from activated macrophages with IC50 value of 6.51 µM. Furthermore, its effect is mediated by reduction of iNOS protein expression, attributable to the inhibitory action of LPS-induced NO production.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Cromonas/farmacologia , Limoninas/farmacologia , Simaroubaceae/química , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Cromonas/química , Cromonas/isolamento & purificação , Relação Dose-Resposta a Droga , Limoninas/química , Limoninas/isolamento & purificação , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Modelos Moleculares , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/biossíntese , Relação Estrutura-AtividadeRESUMO
Endophytic fungi are known as a prolific source for the discovery of structurally interesting and biologically active secondary metabolites, some of which are promising candidates for drug development. In the present study, three anthranoids were isolated from an Alternaria sp. endophytic fungus and evaluated for their antiangiogenic activity in a rat aortic sprouting assay, an ex vivo model of angiogenesis. Of these three compounds, altersolanol (2) was further characterized and found to show a promising activity in ex vivo, in vitro and in vivo angiogenesis asssays. Using human umbilical vein endothelial cells as an in vitro model, the angiogenic effect of 2 was found to occur via suppression of all three main functions of endothelial cells, namely proliferation, tube formation and migration.
Assuntos
Alternaria/química , Inibidores da Angiogênese/isolamento & purificação , Antraquinonas/isolamento & purificação , Endófitos/química , Erythrina/microbiologia , Alternaria/isolamento & purificação , Animais , Antraquinonas/farmacologia , Endófitos/isolamento & purificação , Células Endoteliais da Veia Umbilical Humana , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neovascularização Fisiológica/efeitos dos fármacos , Plantas Medicinais/microbiologia , Ratos , Ratos WistarRESUMO
Gardenia plants have long been used as traditional medicines in various countries including Thailand. In this study, two new 3,4-seco-cycloartane triterpenes, sootependial (1) and sootepenoic acid (2), were isolated from bud exudate of G. sootepensis, together with five known compounds. Their structures were elucidated on the basis of spectroscopic data. Sootependial (1) showed potent cytotoxicity selective to Hep-G2 cell lines and anti-angiogenic activity in ex vivo model (a rat aortic ring sprouting) assay. Furthermore, its angiogenic effect was found to occur mainly by suppressing endothelial cell proliferation and tubule formation, suggesting the potential of 1 as a lead compound for cancer treatment.
Assuntos
Inibidores da Angiogênese/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Aorta/efeitos dos fármacos , Gardenia/química , Exsudatos de Plantas/farmacologia , Triterpenos/farmacologia , Inibidores da Angiogênese/química , Inibidores da Angiogênese/isolamento & purificação , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Aorta/citologia , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Células Hep G2 , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Masculino , Exsudatos de Plantas/química , Exsudatos de Plantas/isolamento & purificação , Brotos de Planta/química , Ratos , Ratos Wistar , Relação Estrutura-Atividade , Triterpenos/química , Triterpenos/isolamento & purificaçãoRESUMO
Twelve naturally occurring 3,4-seco-cycloartane triterpenes (1-12) isolated from Gardenia sootepensis and Gardenia obtusifolia, and eight semi-synthetic derivatives (13-20) were evaluated for their antiangiogenic activity on a rat aortic sprouting assay, an ex vivo model of angiogenesis. Among these compounds, sootepin B (1) displayed the most potent activity in terms of the inhibition of microvessel sprouting from rat aortic rings in a dose-dependent manner with IC(50) value of 4.46 µM. Its angiogenic effect was found to occur via suppression of endothelial cell proliferation and tubular formation, and was likely mediated by regulation (inhibition) of the Erk1/2 signaling pathway.