RESUMO
Like the skin, our hair shows striking changes with age, producing hairs with altered diameter, lustre and texture. The biology of hair aging has focused predominately on various aspects of the hair cycle, follicle size and the fibre produced, but surprisingly the impact of the aging scalp dermal environment on the hair follicle and fibre has been generally overlooked. Hair loss affects both sexes with incidence increasing with age. In men, male pattern-balding (androgenetic alopecia) is driven by androgens and follows a specific pattern of frontotemporal and vertex regression. Women also experience female pattern hair loss (FPHL), presenting as more general, diffuse hair thinning. Hair thinning in women is commonly associated with the menopause, corresponding with other age-related changes in skin. The rapidly growing hair follicle undergoes continued renewal throughout the life span of an individual, where it is exposed to a substantial number of extrinsic and intrinsic stressors. As the hair follicle sits deep within the dermis with its bulb residing in the hypodermis, detrimental age-related changes in the surrounding scalp skin may likely disrupt the hair follicle machinery. The impacts of these changes are unknown, but evidence suggests that scalp skin aging and hair follicle aging go hand-in-hand. Herein, we summarize the evidence that the age-related changes observed in sun-exposed human skin also occur in scalp skin and that these changes are likely to play a contributing role in the aging hair phenotype.
Assuntos
Folículo Piloso/fisiopatologia , Couro Cabeludo/fisiopatologia , Envelhecimento da Pele/fisiologia , Alopecia/fisiopatologia , Animais , Microambiente Celular , Hormônios Esteroides Gonadais/fisiologia , Folículo Piloso/anatomia & histologia , HumanosRESUMO
Stilbenoids, a family of polyphenols known for the complexity of their structure and for their diverse biological activities, occur with a limited but heterogeneous distribution in the plant kingdom. The most prominent stilbene containing plant family, the Vitaceae, represented by the famous wine producing grape vines Vitis vinifera L., is one of the richest sources of novel stilbenes currently known, together with other families, such as Dipterocarpaceae, Gnetaceae and Fabaceae. This review focuses on the distribution of stilbenes and 2-arylbenzofuran derivatives in the plant kingdom, the chemical structure of stilbenes in the Vitaceae family and their taxonomic implication.
Assuntos
Estilbenos , Vitaceae/química , Estrutura Molecular , Estilbenos/química , Estilbenos/isolamento & purificação , Estilbenos/farmacologiaRESUMO
In women, aging leads to reduced hair density and thinner fibers and can result in female-pattern hair loss. However, the impact of the aging dermal environment on female scalp hair follicles remains unclear. In this study, we document in situ changes in 22 women (aged 19-81 years) and primary cultures of dermal fibroblast and dermal sheath cells. In situ, the papillary reticular boundary was indistinguishable in the young scalp but prominent in the scalp of those aged >40 years, accompanied by reduced podoplanin (PDPN) expression, increased versican expression, and changes in collagen organization. Hair follicles were shorter, not reaching the adipose layer. Hyaluronic acid synthase 2 was highly expressed, whereas matrix metalloproteinase 1 was elevated in the dermal papilla and dermal sheath in situ. Primary dermal fibroblast cultures confirmed that matrix metalloproteinase 1 mRNA, MMP1, increased with aging, whereas in dermal sheath cells, hyaluronic acid synthase 2, HAS2, and PDPN increased and α-smooth muscle actin αSMA mRNA decreased. Both exhibited increased cartilage oligomeric protein, COMP mRNA expression. Proteomics revealed an increase in dermal sheath proteins in the dermal fibroblast secretome with aging. In summary, aging female scalp shows striking structural and biological changes in the hair follicle environment that may impact hair growth.
Assuntos
Envelhecimento/patologia , Derme/patologia , Fibroblastos/metabolismo , Folículo Piloso/patologia , Actinas/metabolismo , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Proteína de Matriz Oligomérica de Cartilagem/metabolismo , Células Cultivadas , Derme/citologia , Derme/metabolismo , Feminino , Folículo Piloso/crescimento & desenvolvimento , Folículo Piloso/metabolismo , Humanos , Hialuronan Sintases/metabolismo , Glicoproteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Cultura Primária de Células , Proteômica , Couro Cabeludo , Adulto JovemRESUMO
This review explores medieval, ancient and modern sources for ethnopharmacological uses of Ficus (fig) species, specifically for employment against malignant disease and inflammation. The close connection between inflammatory/infectious and cancerous diseases is apparent both from the medieval/ancient merging of these concepts and the modern pharmacological recognition of the initiating and promoting importance of inflammation for cancer growth. Also considered are chemical groups and compounds underlying the anticancer and anti-inflammatory actions, the relationship of fig wasps and fig botany, extraction and storage of fig latex, and traditional methods of preparing fig medicaments including fig lye, fig wine and medicinal poultices.
Assuntos
Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Ficus/química , Animais , Anti-Inflamatórios/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Ensaios Clínicos como Assunto , Humanos , Inflamação/tratamento farmacológico , Neoplasias/tratamento farmacológicoRESUMO
Morinda citrifolia, commonly called noni, has a long history as a medicinal plant and its use as a botanical dietary supplement has grown tremendously in recent years. This has prompted a concomitant increase in research on the phytochemical constituents and biological activity of noni. A relatively large number of scientific publications on noni have been published in recent years, including a number of review articles. The goals of this review are to provide an updated categorization of the phytochemical constituents found in noni and to provide perspective for its extensive utilization as a major botanical dietary supplement. Included herein are a comprehensive list of known ethnobotanical uses and common names of M. citrifolia, a brief summary of relevant biological studies and a discussion of the safety of noni as a supplement.
Assuntos
Suplementos Nutricionais , Etnobotânica , Morinda/química , Extratos Vegetais/uso terapêutico , Animais , Humanos , Estrutura Molecular , Extratos Vegetais/administração & dosagem , Extratos Vegetais/efeitos adversosRESUMO
Honey bees, Apis mellifera, collect antimicrobial plant resins from the environment and deposit them in their nests as propolis. This behavior is of practical concern to beekeepers since the presence of propolis in the hive has a variety of benefits, including the suppression of disease symptoms. To connect the benefits that bees derive from propolis with particular resinous plants, we determined the identity and botanical origin of propolis compounds active against bee pathogens using bioassay-guided fractionation against the bacterium Paenibacillus larvae, the causative agent of American foulbrood. Eleven dihydroflavonols were isolated from propolis collected in Fallon, NV, including pinobanksin-3-octanoate. This hitherto unknown derivative and five other 3-acyl-dihydroflavonols showed inhibitory activity against both P. larvae (IC50 = 17-68 µM) and Ascosphaera apis (IC50 = 8-23 µM), the fungal agent of chalkbrood. A structure-activity relationship between acyl group size and antimicrobial activity was found, with longer acyl groups increasing activity against P. larvae and shorter acyl groups increasing activity against A. apis. Finally, it was determined that the isolated 3-acyl-dihydroflavonols originated from Populus fremontii, and further analysis showed these compounds can also be found in other North American Populus spp.
Assuntos
Anti-Infecciosos/química , Ascomicetos/efeitos dos fármacos , Abelhas , Paenibacillus larvae/efeitos dos fármacos , Populus/química , Resinas Vegetais/química , Animais , Fracionamento Químico , Flavonóis/química , Testes de Sensibilidade Microbiana , Própole/química , Relação Estrutura-AtividadeRESUMO
A C29-triterpene, beccaridiol (1), a dihydrochalcone natural product, 2',4'-dihydroxy-3-(4-methoxyphenyl)-propiophenone (2), as well as three known compounds, 4'-hydroxy-1',2'-dihydro-beta-ionone, 4'-O-methyldavidigenin (3), and ursolic acid, have been isolated from an EtOAc-soluble extract of the leaves of Diplectria beccariana. Beccaridiol (1) was characterized as an ursane-type 28-nortriterpene possessing an unusual aromatic E-ring by spectroscopic data interpretation. The relative configuration of this unusual isolate was established by analyzing the observed NOESY NMR correlations, and the absolute stereochemistry of 1 was then determined based on the circular dichroism (CD) spectrum of its 2,3-di-p-bromobenzoate (1b) derivative. All isolates were evaluated for their potential cancer chemopreventive properties utilizing a cell culture assay to determine quinone reductase induction.
Assuntos
Melastomataceae/química , Folhas de Planta/química , Triterpenos/isolamento & purificação , Indução Enzimática , NAD(P)H Desidrogenase (Quinona)/biossíntese , Ressonância Magnética Nuclear Biomolecular , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Triterpenos/químicaRESUMO
Activity-guided fractionation of the leaves of Macaranga triloba, using an in vitro bioassay based on the inhibition of cyclooxygenase-2, resulted in the isolation of a rotenoid, 4,5-dihydro-5'alpha-hydroxy-4'alpha-methoxy-6a,12a-dehydro-alpha-toxicarol (1), as well as 12 known compounds, (+)-clovan-2beta,9alpha-diol, ferulic acid, 3,7,3',4'-tetramethylquercetin, 3,7,3'-trimethylquercetin, 3,7-dimethylquercetin, abscisic acid, 1beta,6alpha-dihydroxy-4(15)-eudesmene, 3beta-hydroxy-24-ethylcholest-5-en-7-one, loliolide, scopoletin, taraxerol, and 3-epi-taraxerol. The structure of compound 1 was determined using spectroscopic methods. All isolates were evaluated for their potential to inhibit cyclooxygenases-1 and -2 by measuring PGE(2) production, and to induce quinone reductase in cultured Hepa 1c1c7 mouse hepatoma cells.
Assuntos
Anticarcinógenos/química , Anticarcinógenos/farmacologia , Euphorbiaceae/química , Álcoois/química , Álcoois/isolamento & purificação , Álcoois/farmacologia , Animais , Anticarcinógenos/isolamento & purificação , Linhagem Celular Tumoral , Ciclo-Oxigenase 1 , Ciclo-Oxigenase 2 , Indução Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Concentração Inibidora 50 , Isoenzimas/antagonistas & inibidores , Neoplasias Hepáticas Experimentais , Proteínas de Membrana , Camundongos , Estrutura Molecular , NAD(P)H Desidrogenase (Quinona)/biossíntese , Ressonância Magnética Nuclear Biomolecular , Folhas de Planta/química , Prostaglandina-Endoperóxido SintasesRESUMO
We present stilbenoid profiles of canes from 16 grapevines. Fifteen stilbenoids were obtained through isolation and structure identification using MS, NMR, and [α](D) or as commercial standards. An HPLC-UV method for the simultaneous quantification of nine of these stilbenoids was developed and applied to canes of Vitis amurensis, Vitis arizonica, Vitis berlandieri, Vitis betulifolia, Vitis cinerea, Vitis × champini, Vitis × doaniana, Vitis labrusca, Vitis candicans (syn. Vitis mustangensis), Vitis riparia, Vitis rupestris, Vitis vinifera, Muscadinia rotundifolia, and a V. vinifera × M. rotundifolia hybrid. In these species, E-ampelopsin E, E-amurensin B, E-piceid, E-piceatannol, E-resveratrol, E-resveratroloside, E-ε-viniferin, E-ω-viniferin, and E-vitisin B were quantified, when found in sufficient amounts. Total concentrations ranged from ~2.2 to 19.5 g/kg of dry weight. Additional stilbenoids, E-3,5,4'-trihydroxystilbene 2-C-glucoside, Z-ampelopsin E, Z-trans-miyabenol C, E-trans-miyabenol C, scirpusin A, and Z-vitisin B, were identified but not quantified. Our results indicate that canes, particularly those of non-vinifera species, have substantial quantities of valuable, health-promoting stilbenoids.
Assuntos
Estilbenos/química , Vitis/química , Benzofuranos/química , Cromatografia Líquida de Alta Pressão , Flavonoides/química , Glucosídeos/química , Espectroscopia de Ressonância Magnética , Fenóis/química , Resveratrol , Vitis/classificaçãoRESUMO
Wine is a major dietary source of numerous potentially health promoting stilbenoids that have been the subject of many qualitative and quantitative studies. However, our initial HPLC-MS analyses of crude wine samples demonstrated the presence of compounds with molecular weights matching characteristic stilbenoid dimers, trimers, and tetramers that were unaccounted for in the literature. Due to the likelihood that these are known compounds, a chemical dereplication method is highly desirable. We developed such a method using LC-DAD-MS monitored fractionation steps, using adsorption and centrifugal partition chromatography (CPC), to obtain fractions rich in stilbenoids for analysis in stopped-flow LC-NMR. (1)H NMR spectra and MS data were cross-referenced with our laboratory database and the literature for identification. This method yielded highly useful structural information, allowing the characterization of previously unidentified stilbenoids in wine, ampelopsin C, isohopeaphenol, quadrangularin A, and E-ω-viniferin. These results demonstrate the usefulness of stop-flow LC-NMR in conjunction with LC-MS guided fractionation for the dereplication of compounds of interest in general, and specifically for expanding the current knowledge of wine chemistry.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Espectroscopia de Ressonância Magnética/métodos , Estilbenos/análise , Vinho/análise , Espectrometria de MassasRESUMO
The phytochemical study of the root extract of the stilbenoid-rich Vitis riparia×Vitis berlandieri grapevine was carried out by centrifugal partition chromatography (CPC). For this reason, we developed a new elution mode we named back-step, which allowed us to obtain cleaner fractions and a more efficient separation process when used in conjunction with a classical elution approach. Three hydroxystilbenes: (E)-resveratrol, (E)-É-viniferin and (E)-vitisin C, with greater than 90% purity were thus obtained through such process, with minimal sample handling and purification steps. Online coupling of CPC to ESI mass spectrometry was used for optimization of the separation parameters and to facilitate the characterization of the stilbenoids. This study details the first phytochemical investigation of stilbenoids from the hybrid species together with a new elution mode able to widen the range of ARIZONA biphasic systems.
Assuntos
Centrifugação/métodos , Cromatografia Líquida/métodos , Espectrometria de Massas/métodos , Extratos Vegetais/isolamento & purificação , Estilbenos/isolamento & purificação , Vitis/químicaRESUMO
Stilbenoid compounds consist of a family of resveratrol derivatives. They have demonstrated promising activities in vitro and in vivo that indicate they may be useful in the prevention of a wide range of pathologies, such as cardiovascular diseases and cancers, as well have anti-aging effects. More recently stilbenoid compounds have shown promise in the treatment and prevention of neurodegenerative disorders, such as Huntington's, Parkinson's, and Alzheimer's diseases. This paper primarily focuses on the impact of stilbenoids in Alzheimer's disease and more specifically on the inhibition of ß-amyloid peptide aggregation.
Assuntos
Doenças Neurodegenerativas/prevenção & controle , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Estilbenos/metabolismo , Estilbenos/uso terapêutico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/prevenção & controle , Animais , Humanos , Doenças Neurodegenerativas/metabolismo , Fármacos Neuroprotetores/química , Resveratrol , Estilbenos/químicaRESUMO
PURPOSE: Pomegranate fruit extracts (PFEs) possess polyphenolic and other compounds with antiproliferative, pro-apoptotic and anti-inflammatory effects in prostate, lung, and other cancers. Because nuclear transcription factor-kB (NF-kB) is known to regulate cell survival, proliferation, tumorigenesis, and inflammation, it was postulated that PFEs may exert anticancer effects at least in part by modulating NF-kB activity. EXPERIMENTAL DESIGN: The authors investigated the effect of a novel, defined PFE consisting of both fermented juice and seed oil on the NF-kB pathway, which is constitutively active in aggressive breast cancer cell lines. The effects of the PFE on NF-kB-regulated cellular processes such as cell survival, proliferation, and invasion were also examined. RESULTS: Analytical characterization of the bioactive components of the PFE revealed active constituents, mainly ellagitannins and phenolic acids in the aqueous PFE and conjugated octadecatrienoic acids in the lipid PFE derived from seeds.The aqueous PFE dose-dependently inhibited NF-kB-dependent reporter gene expression associated with proliferation, invasion, and motility in aggressive breast cancer phenotypes while decreasing RhoC and RhoA protein expression. CONCLUSION: Inhibition of motility and invasion by PFEs, coincident with suppressed RhoC and RhoA protein expression, suggests a role for these defined extracts in lowering the metastatic potential of aggressive breast cancer species.
Assuntos
Neoplasias da Mama/patologia , Movimento Celular/efeitos dos fármacos , Frutas/química , Lythraceae/química , Extratos Vegetais/farmacologia , Ácido 12-Hidroxi-5,8,10,14-Eicosatetraenoico/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dinoprostona/metabolismo , Feminino , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Humanos , Ácidos Hidroxieicosatetraenoicos/metabolismo , Leucotrieno B4/metabolismo , NF-kappa B/metabolismo , Subunidade p50 de NF-kappa B/metabolismo , Invasividade Neoplásica/patologia , Fitoterapia , Fator de Transcrição RelA/metabolismo , Proteínas rho de Ligação ao GTP/genética , Proteínas rho de Ligação ao GTP/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo , Proteína de Ligação a GTP rhoCRESUMO
The class of steroid-like compounds designated cardiac glycosides includes well-known drugs such as digoxin, digitoxin, and ouabain. Their continued efficacy in treatment of congestive heart failure and as anti-arrhythmic agents is well appreciated. Less well known, however, is the emerging role of this category of compounds in the prevention and/or treatment of proliferative diseases such as cancer. New findings within the past five years have revealed these compounds to be involved in complex cell-signal transduction mechanisms, resulting in selective control of human tumor but not normal cellular proliferation. As such, they represent a promising form of targeted cancer chemotherapy. New clinical studies of their anticancer potential as single or adjuvant treatments may provide insight into these potentially valuable therapeutic options. This review focuses on recent findings on cellular pharmacology of cardiac glycosides as they relate to treatment of human cancer and attempts to explain why these agents have been overlooked in the past.
Assuntos
Antineoplásicos/uso terapêutico , Glicosídeos Cardíacos/uso terapêutico , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Glicosídeos Cardíacos/química , Glicosídeos Cardíacos/metabolismo , Glicosídeos Cardíacos/farmacologia , Desenho de Fármacos , Inibidores do Crescimento/química , Inibidores do Crescimento/metabolismo , Inibidores do Crescimento/farmacologia , Humanos , Camundongos , Neoplasias/prevenção & controle , Ratos , Receptores de Estrogênio/metabolismo , Transdução de Sinais , ATPase Trocadora de Sódio-Potássio/fisiologia , Especificidade da EspécieRESUMO
Two new compounds, a cyclopenta[bc]benzopyran, ponapensin (1), and an aglaialactone, 5,6-desmethylenedioxy-5-methoxy-aglalactone (2), together with nine known compounds were isolated from the CHCl(3) soluble extract of the leaves and twigs of Aglaia ponapensis. Their structures were established by spectroscopic data interpretation. Ponapensin (1) exhibited significant NF-kappaB inhibitory activity in an Elisa assay, and was found to be more potent than the positive control rocaglamide. All of the compounds isolated were also tested in a panel of human cancer cell lines, with the known sterol E-volkendousin (3) and methyl rocaglate (aglafoline) found to be the only active substances.
Assuntos
Aglaia/química , Benzopiranos/química , Benzopiranos/farmacologia , Compostos Heterocíclicos com 3 Anéis/química , Compostos Heterocíclicos com 3 Anéis/farmacologia , NF-kappa B/antagonistas & inibidores , Benzofuranos/química , Benzofuranos/isolamento & purificação , Benzofuranos/farmacologia , Benzopiranos/isolamento & purificação , Linhagem Celular Tumoral , Ensaio de Imunoadsorção Enzimática , Compostos Heterocíclicos com 3 Anéis/isolamento & purificação , Humanos , Estrutura Molecular , Folhas de Planta/químicaRESUMO
Morinda citrifolia, commonly known as noni, has a long history of utilization throughout much of tropical Polynesia and is considered to be the second most important medicinal plant in the Hawaiian Islands. Recently, the use of noni as a dietary supplement in the United States has greatly increased. Bioassay-guided fractionation of a dichloromethane-soluble partition of a MeOH extract of noni fruits has led to the isolation of an extremely potent quinone reductase inducer, 2-methoxy-1,3,6-trihydroxyanthraquinone (1). This new anthraquinone (1) was nearly 40 times more potent than a positive control, l-sulforaphane. Furthermore, compound 1 demonstrated no discernible cytotoxicity at the highest dose tested. In addition to compound 1, 11 known compounds were also isolated and identified in the present investigation. This is the first report of the isolation of anthraquinones from noni fruits.
Assuntos
Antraquinonas/isolamento & purificação , Anticarcinógenos/isolamento & purificação , Morinda/química , NAD(P)H Desidrogenase (Quinona)/antagonistas & inibidores , Plantas Medicinais/química , Animais , Antraquinonas/química , Antraquinonas/farmacologia , Antraquinonas/toxicidade , Anticarcinógenos/química , Anticarcinógenos/farmacologia , Anticarcinógenos/toxicidade , Frutas/química , Concentração Inibidora 50 , Isotiocianatos , Camundongos , Estrutura Molecular , Sulfóxidos , Tiocianatos/farmacologia , Tiocianatos/toxicidade , Células Tumorais CultivadasRESUMO
Purification of a n-BuOH-soluble partition of the MeOH extract of Morinda citrifolia (Noni) fruits led to the isolation of two new iridoid glucosides, 6alpha-hydroxyadoxoside (1) and 6beta,7beta-epoxy-8-epi-splendoside (2), as well as 17 known compounds, americanin A (3), narcissoside (4), asperuloside, asperulosidic acid, borreriagenin, citrifolinin B epimer a, citrifolinin B epimer b, cytidine, deacetylasperuloside, dehydromethoxygaertneroside, epi-dihydrocornin, d-glucose, d-mannitol, methyl alpha-d-fructofuranoside, methyl beta-d-fructofuranoside, nicotifloroside, and beta-sitosterol 3-O-beta-d-glucopyranoside. The structures of the new compounds were determined by spectroscopic data interpretation. Compound 4, borreriagenin, cytidine, deacetylasperuloside, dehydromethoxygaertneroside, epi-dihydrocornin, methyl alpha-d-fructofuranoside, and methyl beta-d-fructofuranoside were isolated for the first time from M. citrifolia. The antioxidant activity was evaluated for all isolates in terms of both DPPH and ONOO(-) bioassays. The neolignan, americanin A (3), was found to be a potent antioxidant in these assays.
Assuntos
Antioxidantes/isolamento & purificação , Iridoides/isolamento & purificação , Morinda/química , Plantas Medicinais/química , Antioxidantes/química , Antioxidantes/farmacologia , Compostos de Bifenilo , Monoterpenos Ciclopentânicos , Dioxinas/química , Dioxinas/isolamento & purificação , Dioxinas/farmacologia , Frutas/química , Glucosídeos/química , Glucosídeos/isolamento & purificação , Glucosídeos/farmacologia , Iridoides/química , Iridoides/farmacologia , Estrutura Molecular , Picratos/farmacologia , Piranos/química , Piranos/isolamento & purificação , Piranos/farmacologiaRESUMO
A highly oxygenated phenolic spiroketone, limnophilaspiroketone (1), was isolated from the aerial parts of Limnophila geoffrayi collected in Thailand. The structure of 1 was determined based on spectroscopic data interpretation. This novel isolate, obtained as a major secondary metabolite constituent, was verified as a racemate using the Mosher ester method.
Assuntos
Fenóis/isolamento & purificação , Plantas Medicinais/química , Scrophulariaceae/química , Animais , Camundongos , Estrutura Molecular , Fenóis/química , Tailândia , Células Tumorais CultivadasRESUMO
Previous collaborative work by our group has led to the discovery of several plant isolates and derivatives with activities in in vivo models of cancer chemoprevention, including deguelin, resveratrol, bruceantin, brassinin, 4'-bromoflavone, and oxomate. Using a panel of in vitro bioassays to monitor chromatographic fractionation, a diverse group of plant secondary metabolites has been identified as potential cancer chemopreventive agents from mainly edible plants. Nearly 50 new compounds have been isolated as bioactive principles in one or more in vitro bioassays in work performed over the last five years. Included among these new active compounds are alkaloids, flavonoids, stilbenoids, and withanolides, as well as a novel stilbenolignan and the first representatives of the norwithanolides, which have a 27-carbon atom skeleton. In addition, over 100 active compounds of previously known structure have been obtained. Based on this large pool of potential cancer chemopreventive compounds, structure-activity relationships are discussed in terms of the quinone reductase induction ability of flavonoids and withanolides and the cyclooxygenase-1 and -2 inhibitory activities of flavanones, flavones and stilbenoids. Several of the bioactive compounds were found to be active when evaluated in a mouse mammary organ culture assay, when used as a secondary discriminator in our work. The compounds (2 S)-abyssinone II, (2 S)-2',4'-dihydroxy-2"-(1-hydroxy-1-methylethyl)dihydrofuro[2,3- h]-flavanone, 3'-[gamma-hydroxymethyl-( E)-gamma-methylallyl]-2,4,2',4'-tetrahydroxychalcone 11'- O-coumarate, isolicoflavonol, isoliquiritigenin, and ixocarpalactone A are regarded as promising leads as potential cancer chemopreventive agents.