RESUMEN
Cancer is one of the most important causes of death worldwide. Solid tumors represent the vast majority of cancers (>90%), and the chemotherapeutic agents used for their treatment are still characterized by variable efficacy and toxicity. Sesquiterpenes are a group of natural compounds that have shown a wide range of biological activities, including cytotoxic and antiparasitic activity, among others. The antiproliferative activity of natural sesquiterpenes, tessaric acid, ilicic acid, and ilicic alcohol and their semisynthetic derivatives against HeLa, T-47D, WiDr, A549, HBL-100, and SW1573 cell lines were evaluated. The effect of the compounds on Trypanosoma cruzi epimastigotes was also assessed. The selectivity index was calculated using murine splenocytes. Derivatives 13 and 15 were the most antiproliferative compounds, with GI50 values ranging between 5.3 (±0.32) and 14 (±0.90) µM, in all cell lines tested. The presence of 1,2,3-triazole groups in derivatives 15−19 led to improvements in activity compared to those corresponding to the starting natural product (3), with GI50 values ranging between 12 (±1.5) and 17 (±1.1) µM and 16 being the most active compound. In relation to the anti-T. cruzi activity, derivatives 7 and 16 obtained from tessaric acid and ilicic acid were among the most active and selective compounds with IC50 values of 9.3 and 8.8 µM (SI = 8.0 and 9.4), respectively.
Asunto(s)
Antineoplásicos , Sesquiterpenos , Trypanosoma cruzi , Animales , Antineoplásicos/farmacología , Células HeLa , Humanos , Ratones , Sesquiterpenos/farmacología , Relación Estructura-ActividadRESUMEN
DNA polymerases are enzymes that play a crucial role in DNA metabolism such as replication, repair, transcription, recombination, and chromosome segregation during mitosis. Herein we report the isolation of a new iridoid (6-epi-catalpol, 2) and per-O-acetyl-verbascoside (11) from aerial part of Buddleja cordobensis Grisebach (Buddlejaceae). From compound 2, we have obtained eight compounds by chemical transformation. This group of compounds at a concentration of 500µM was assayed against Taq DNA polymerase. Compound 11 (per-O-acetyl-verbascoside) was the most active with an IC50 of 1.21±0.18µM; compounds 9, 2 and 8 were strong inhibitors with IC50 values of 5.57±0.70, 21.62±0.22 and 78.13±0.93µM, respectively. Compounds 11 and 9 could be a leader structures to development new anticancer chemotherapy medicines and a useful tool to investigate DNA polymerase activity.
Asunto(s)
Inhibidores Enzimáticos/farmacología , Glucósidos/farmacología , Fenoles/farmacología , Polimerasa Taq/antagonistas & inhibidores , Concentración 50 InhibidoraRESUMEN
RATIONALE: Sauroxine and N-demethylsauroxine are lycodine-type Lycopodium alkaloids. In recent years, Lycopodium alkaloids have gained significant interest due to their unique skeletal characteristics as well as due to their acetylcholinesterase activity. It is known that drugs that inhibit acetylcholinesterase can be used to treat the early stages of Alzheimer's disease. METHODS: Sauroxine and N-demethylsauroxine were isolated from the aerial parts of Huperzia saururus (Lam.) Trevis. Electron ionization mass spectrometry (EI-MS) (low resolution) and collision-induced dissociation tandem mass spectrometry (CID-MS/MS) fragmentation was conducted using an ion trap, GCQ Plus mass spectrometer with MS/MS. Electron ionization high-resolution mass spectrometry (EI-HRMS) was performed in a magnetic sector mass spectrometer (Micromass VG). RESULTS: Using GC/EI-CID-MS/MS we obtained different fragmentation routes that connect all the ionic populations. In addition, the use of EI-HRMS allowed us to measure the exact masses of all the fragment ions, and, with all this information gathered, we tried to establish a fragmentation scheme concordant with the ascendant and descendant species. CONCLUSIONS: The mass spectrometry studies presented in this work complete our mass studies of Lycopodium alkaloids. The mass spectrometry work presented has been very useful to confirm the structures as well as to support the biogenetic relationships between the lycodine-type Lycopodium alkaloids: sauroxine and N-demethylsauroxine.
Asunto(s)
Alcaloides/química , Compuestos Heterocíclicos de 4 o más Anillos/química , Lycopodium/química , Espectrometría de Masa por Ionización de Electrospray/métodos , Cromatografía de Gases y Espectrometría de Masas/métodos , Iones/química , Extractos Vegetales/química , Espectrometría de Masas en Tándem/métodosRESUMEN
Coumarin derivatives were prepared using natural products isolated from plants belonging in the Pterocaulon genus (Asteraceae) and commercial drugs. Some molecules have displayed interesting activity against myeloid murine leukemia virus-reverse transcriptase (MMLV-RT) (compounds 20 and 28 produced inhibition with IC50 values of 38.62 and 50.98 µM, respectively) and Taq DNA polymerase (analogues 13 and 14 produced inhibition with IC50 values of 48.08 and 57.88 µM, respectively). Such inhibitors may have importance as antiretroviral chemotherapeutic agents and also in the development of anticancer drugs.
Asunto(s)
Cumarinas/química , Cumarinas/farmacología , Inhibidores de la Transcriptasa Inversa/química , Inhibidores de la Transcriptasa Inversa/farmacología , Polimerasa Taq/antagonistas & inhibidores , Animales , Asteraceae/química , Línea Celular Tumoral , Activación Enzimática/efectos de los fármacos , Concentración 50 Inhibidora , Ratones , Modelos Biológicos , Estructura Molecular , Virus de la Leucemia Murina de Moloney/enzimología , Preparaciones de Plantas/química , Inhibidores de la Transcriptasa Inversa/síntesis químicaRESUMEN
Two iridoid scaffolds were synthesized enantioselectively using as key step an l-proline-catalyzed alpha-formyl oxidation. The in vitro antiproliferative activities were evaluated against a representative panel of human solid tumor cell lines. Both iridoids induced considerably growth inhibition in the range 0.38-1.86muM. Cell cycle studies for these compounds showed the induction of cell cycle arrest at the G(1) phase. This result was consistent with a decrease in the expression of cyclin D1. Damaged cells underwent apoptosis as indicated by specific Annexin V staining.
Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Proliferación Celular/efectos de los fármacos , Glucósidos/química , Glucósidos/farmacología , Iridoides/química , Iridoides/farmacología , Anexina A5/metabolismo , Antineoplásicos/síntesis química , Western Blotting , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Inhibidores Enzimáticos/metabolismo , Glucósidos/síntesis química , Humanos , Glucósidos Iridoides , Iridoides/síntesis química , Modelos Moleculares , Conformación Molecular , Relación Estructura-ActividadRESUMEN
A series of analogs were synthesized in a straightforward manner from naturally available sesquiterpenes ilicic acid and tessaric acid. The in vitro antiproliferative activities were examined in the human solid tumor cell lines A2780, HBL-100, HeLa, SW1573, T-47D and WiDr. The most potent analog induced considerably growth inhibition in the range 1.9-4.5 microM. Cell cycle studies for tessaric acid derivatives indicated a prominent arrest of the cell cycle at the G(2)/M phase. Damage to the cells was permanent as determine by the so called 24+24 drug schedule.
Asunto(s)
Antineoplásicos/química , Sesquiterpenos/química , Antineoplásicos/síntesis química , Antineoplásicos/farmacología , División Celular , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Fase G2 , Humanos , Neoplasias/tratamiento farmacológico , Relación Estructura-Actividad Cuantitativa , Sesquiterpenos/síntesis química , Sesquiterpenos/farmacologíaRESUMEN
Secondary metabolites play a major role in the adaptation of plants to the environment. Furan neo-clerodane diterpenes are characteristic secondary metabolites in Baccharis flabellata Hook. & Arn. var. flabellata. One of the main compounds is the diene ent-15,16-epoxy-19-hydroxy-1,3,13(16),14-clerodatetraen-18-oic acid (DAC). In this work a new dimeric compound (DACD) has been isolated and identified by NMR and MS techniques. The presence of other minor dimers was also observed in the same plant methanolic extracts. Assuming that they may be the products of [4â¯+â¯2] condensation of two monomeric moieties, the formation of adducts by photochemical dimerization was checked by inducing the in vitro [4â¯+â¯2] cycloaddition of DAC. Moreover, the DAC and DACD accumulation rates in aerial parts of B. flabellata specimens were analyzed monthly during a complete phenological cycle. The accumulation of monomer depends on the plant phonological stage; meanwhile the dimer proportion arises in detriment of the monomer as the solar UV radiation increases. Since plants exposed to strong UV intensities produce radical species, the scavenger properties of these compounds toward reactive nitrogen species (RNS), and reactive oxygen species (ROS), were analyzed. Albeit DAC and DACD show significant superoxide radical scavenger activities, the monomer proved to be more effective than the dimer toward ROS, while DACD was an excellent RNS scavenger.
Asunto(s)
Baccharis/química , Diterpenos de Tipo Clerodano/química , Especies de Nitrógeno Reactivo/química , Especies Reactivas de Oxígeno/química , Rayos Ultravioleta , Baccharis/metabolismo , Reacción de Cicloadición , Dimerización , Depuradores de Radicales Libres/química , Espectroscopía de Resonancia Magnética , Componentes Aéreos de las Plantas/química , Componentes Aéreos de las Plantas/metabolismo , Extractos Vegetales/químicaRESUMEN
In order to establish structure-activity relationships, nine neo-clerodane diterpenes isolated from the acetone extract of aerial parts of Baccharis flabellata Hook & Arn var. fabellata were assayed for antifeedant activity against Tribolium castaneum (Coleoptera: Tenebrionidae). Compounds exhibiting maximal antifeedant activities showed an alpha,beta-unsaturated carbonyl group on the decalin portion and a furan ring at the side chain. Stereoelectronic studies indicate that the distance between the furan heteroatom and the more electrophilic carbon of the decaline moiety, as well as the electrostatic charge on that atom, were important features for antifeedant activity. Compounds possesing an alpha,beta,gamma,delta-unsaturated carbonyl group or an acetoxyl group at C-2, were inactive. Theoretical calculations were performed in order to find some structure-activity relationships.
Asunto(s)
Baccharis/química , Diterpenos de Tipo Clerodano/química , Diterpenos de Tipo Clerodano/farmacología , Tribolium/efectos de los fármacos , Animales , Diterpenos de Tipo Clerodano/aislamiento & purificación , Conducta Alimentaria/efectos de los fármacos , Conformación Molecular , Resonancia Magnética Nuclear Biomolecular , Rotación Óptica , Espectrometría de Masa por Ionización de Electrospray , Espectrofotometría Ultravioleta , Espectroscopía Infrarroja por Transformada de Fourier , Relación Estructura-Actividad , Tribolium/fisiologíaRESUMEN
Flavonoids have attracted great interest due to their possible anticancer activities. Here we investigated the antiproliferative activity of the flavonoids isolated from Baccharis scandens against human leukemia cell lines and found that the methoxyflavonoid gardenin B was the most cytotoxic compound against HL-60 and U-937 cells, showing IC50 values between 1.6 and 3.0 µM, but had no significant cytotoxic effects against quiescent or proliferating human peripheral blood mononuclear cells. These effects on viability were accompanied by the concentration- and time-dependent appearance of apoptosis as evidenced by DNA fragmentation, formation of apoptotic bodies and a sub-G1 ratio increase. Comparative studies with the best-studied bioflavonoid quercetin indicate that gardenin B is a more cytotoxic and more apoptotic inducer than quercetin. Cell death induced by gardenin B was associated with: (i) a significant induction of caspase-2, -3, -8 and -9 activities; (ii) cleavage of the initiator caspases (caspase-2, -8 and -9), of the executioner caspase-3, and of poly(ADP-ribose) polymerase; and (iii) a concentration-dependent reactive oxygen species generation. In conclusion, apoptosis induced by gardenin B is associated with activation of both the extrinsic and the intrinsic apoptotic pathways of cell death and occurs through a mechanism that is independent of the generation of reactive oxygen species.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Caspasas/metabolismo , Flavonas/farmacología , Leucemia/tratamiento farmacológico , Especies Reactivas de Oxígeno/metabolismo , Antineoplásicos Fitogénicos/química , Baccharis/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Flavonas/química , Células HL-60 , Humanos , Leucemia/metabolismo , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Poli(ADP-Ribosa) Polimerasas/metabolismoRESUMEN
The preventive effect of natural xanthanolides as well as a series of synthetic derivatives on ulcer formation induced by absolute ethanol in rats was examined. Among the compounds tested, xanthatin gave the strongest protective activity. The inhibitory action exerted by this molecule on the lesions induced by 0.6N HCl and 0.2N NaOH was highly significant, reducing ulceration in the range of 58-96% at a dose from 12.5 to 100mg/kg. These results appear to confirm that the presence of a non-hindered alpha,beta-unsaturated carbonyl group seems to be an essential structural requirement for the gastric cytoprotective activity of these compounds. In order to explore this possibility, a theoretical conformational analysis was performed. We suggest that the mechanism of protection would involve, at least in part, a nucleophylic attack of the sulfhydryl group from the biological molecules present in the gastric mucosa to electrophylic carbons accessible in suitable Michael acceptors.
Asunto(s)
Antiulcerosos/farmacología , Sesquiterpenos/farmacología , Xanthium/química , Animales , Antiulcerosos/química , Depresores del Sistema Nervioso Central , Fenómenos Químicos , Química Física , Etanol , Ácido Clorhídrico , Espectroscopía de Resonancia Magnética , Masculino , Modelos Moleculares , Conformación Molecular , Método de Montecarlo , Extractos Vegetales/química , Ratas , Ratas Wistar , Sesquiterpenos/química , Hidróxido de Sodio , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/prevención & control , Relación Estructura-ActividadRESUMEN
Allelochemical effects were observed when Tribolium castaneum (Herbst) adults were treated with Baccharis salicifolia (Ruiz & Pavon) Pers essential oil. The main biological activities were toxicity and repellence. Terpenes present in the essential oil were identified by GC-MS, and some authentic samples were tested to assess their activity individually. The most acutely toxic compounds after 3 days were beta-pinene and pulegone. Most of the monoterpenes elicited symptoms indicative of neurotoxicity. The most repellent compound was alpha-terpineol. Toxic and repellent effects of chemical derivatives of the major sesquiterpene present in B salicifolia essential oil, as well as a series of monoterpenes, were evaluated in order to investigate structure-activity relationships. The reduced derivatives of the monoterpenes and sesquiterpenes were more repellent that their carbonyl analogues. In addition, unsaturation in the germacrane skeleton enhanced repellent activity.
Asunto(s)
Baccharis/química , Repelentes de Insectos , Insecticidas , Aceites Volátiles/química , Aceites Volátiles/farmacología , Tribolium/fisiología , Animales , Estructura Molecular , Monoterpenos/química , Monoterpenos/farmacología , Sesquiterpenos/química , Sesquiterpenos/farmacologíaRESUMEN
To validate the potential as added-value resources of Asteraceae and Labiatae species of Argentinean semi-arid lands, we have selected 13 of their major terpenoids belonging to several chemical classes and tested their insect antifeedant and toxic activity on the herbivorous insects Spodoptera littoralis and Leptinotarsa decemlineata. The antifeedant effects of the test compounds were structure- and species-dependent. The most active antifeedant to L. decemlineata was the eudesmane sesquiterpene gamma-costic acid (13), followed by the labdane diterpene 2alpha,3alpha-dihydroxycativic acid (8), the clerodane diterpenes 6-acetylteucjaponin B (5), bacchotricuneatin A (1), bartemidiolide (7), butanolide (4), and the sesquiterpenes ilicic acid (11) and tessaric acid (10) (eudesmane and eremophilane type, respectively). S. littoralis was only affected by the clerodanes and showed the strongest response to salviarin (3) and 5, followed by hawtriwaic acid (6) and 12-epi-bacchotricuneatin A (2). Orally injected S. littoralis larvae were negatively affected by 5. Most of the diterpenes had selective cytotoxic effects to insect-derived Sf9 cells with the clerodane 1 being the most active, followed by the eudesmane costic acid (12), the only cytotoxic sesquiterpene. None of these compounds was cytotoxic to mammalian CHO cells.
Asunto(s)
Asteraceae/química , Lamiaceae/química , Sesquiterpenos/química , Terpenos/química , Alimentación Animal , Animales , Antiinfecciosos , Argentina , Asteraceae/clasificación , Asteraceae/parasitología , Clima Desértico , Insectos/patogenicidad , Lamiaceae/clasificación , Lamiaceae/parasitología , Enfermedades de las Plantas/parasitología , Sesquiterpenos/toxicidad , Spodoptera/efectos de los fármacos , Spodoptera/patogenicidad , Terpenos/toxicidadRESUMEN
Two clerodane-type diterpene glycosides esters, which were studied as peracetyl derivatives, together with the known diterpene marrubiagenine, were isolated from the aerial part of Baccharis sagittalis (Less). Their structures were established by spectroscopic methods. Antifeedant activity toward Tenebrio molitor larvae of the isolated compounds along with six other diterpenes was evaluated and some structure-antifeedant bioactivity relationships are reported.
Asunto(s)
Baccharis/química , Diterpenos de Tipo Clerodano , Diterpenos/química , Diterpenos/aislamiento & purificación , Diterpenos/farmacología , Insecticidas/aislamiento & purificación , Insecticidas/farmacología , Animales , Conducta Alimentaria/efectos de los fármacos , Insecticidas/química , Larva/efectos de los fármacos , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Estructura Molecular , Componentes Aéreos de las Plantas/química , Tenebrio/efectos de los fármacosRESUMEN
Synthetic coumarins were prepared in high yields using ionic liquids as an environmental friendly alternative. 3,4-Dimethyl-7-hydroxycoumarin (3ab) and 3-isopropyl-4-methyl-5,7-dihydroxycoumarin (3bc) showed interesting activity against Taq DNA polymerase with IC50 values of 115.7 microM and 82.2 microM, respectively. Also, 4-methyl-7-hydroxycoumarin (3aa) and 4-methyl-5,7-dihydroxycoumarin (3ba) exhibited inhibitory activity against MMLV-RT with IC50 values of 23.5 microM and 18.3 microM, respectively. These inhibitors could have importance as antiretroviral chemotherapeutic agents and also for the development of antitumor drugs.
Asunto(s)
Cumarinas/síntesis química , Inhibidores Enzimáticos/síntesis química , Extractos Vegetales/síntesis química , Cumarinas/química , Cumarinas/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Estructura Molecular , Extractos Vegetales/química , Extractos Vegetales/farmacología , Polimerasa Taq/antagonistas & inhibidoresRESUMEN
Using several reactions that include homologations and asymmetric epoxidations as well as Ugi and Huisgen couplings, we generated a small focused library of new derivatives from the labdane-type diterpene grindelic acid. These compounds were evaluated as cytotoxic agents against a panel of five human solid tumor cell lines (HBL-100, HeLa, SW1573, T-47D, and WiDr). The presence of the diamide functionalizations enhanced the cytotoxic effect. N-Benzyl-N-(1-(benzylamino)-2-methyl-1-oxopropan-2-yl)grindelicamide, proved to be the most active product in all cell lines tested, with values of 0.95 (±0.38) µM against HBL-100 cells.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Productos Biológicos/farmacología , Diterpenos/química , Antineoplásicos Fitogénicos/síntesis química , Antineoplásicos Fitogénicos/química , Productos Biológicos/síntesis química , Productos Biológicos/química , Proliferación Celular/efectos de los fármacos , Diterpenos/síntesis química , Diterpenos/farmacología , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Células HeLa , Humanos , Estructura Molecular , Relación Estructura-Actividad , Células Tumorales CultivadasRESUMEN
In this study, we synthesized a series of phenylpropanoic acid derivatives based on modifications at four selected points of the molecular scaffold. The in vitro antiproliferative activities of the compounds were examined in representative human solid tumor cell lines. A SAR was established pointing out the relevance of the substituents. The best activity profiles were obtained for the derivatives bearing more lipophilic esters (GI50 3.1-21 microM).
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Fenilpropionatos/farmacología , Antineoplásicos Fitogénicos/síntesis química , Antineoplásicos Fitogénicos/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Cromatografía en Capa Delgada , Ensayos de Selección de Medicamentos Antitumorales , Cromatografía de Gases y Espectrometría de Masas , Humanos , Indicadores y Reactivos , Espectroscopía de Resonancia Magnética , Fenilpropionatos/síntesis química , Fenilpropionatos/química , Espectrofotometría Infrarroja , Relación Estructura-ActividadRESUMEN
The aim of the present study was to determine whether dehydroleucodine, xanthatin and 3-benzyloxymethyl-5H-furan-2-one inhibit the activation of human leukemic LAD2 mast cells induced by compound 48/80 or the calcium ionophore A23187. LAD2 cells were preincubated in the presence of test drugs and then challenged with the secretagogues. This study provides the first evidence in favor of the view that dehydroleucodine and xanthatin inhibit the degranulation of LAD2 cells, thus acting as human mast cell stabilizers. These molecules could be effective in the treatment of human diseases associated with inappropriate mast cell activation.
Asunto(s)
Furanos/farmacología , Lactonas/farmacología , Mastocitos/metabolismo , Sesquiterpenos/farmacología , Calcimicina/farmacología , Ionóforos de Calcio/farmacología , Degranulación de la Célula/efectos de los fármacos , Línea Celular Tumoral , Humanos , Cinética , Leucemia de Mastocitos/metabolismo , Leucemia de Mastocitos/patología , Mastocitos/fisiología , Mastocitos/ultraestructura , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , beta-N-Acetilhexosaminidasas/metabolismo , p-Metoxi-N-metilfenetilamina/farmacologíaRESUMEN
In this work, a novel catalpol derivative (6,10,2',6'-tetraacetyl-O-catalpol), which was previously obtained by our group and shown experimentally to inhibit a type of Taq DNA polymerase, was studied in silico. Studies of the interaction of 6,10,2',6'-tetraacetyl-O-catalpol with the Klentaq fragment of the Taq DNA polymerase I from Thermus aquaticus helped to elucidate the mechanism of inhibition of the enzyme, and offered valuable information that can be used to propose substrate structural modifications aimed at increasing the binding affinity. Classical and semi-empirical methods were used to characterize the conformational preferences of this organic compound in solution. Using docking simulations, the most probable binding mode was found, and the stabilities of the docked solutions were tested in a series of molecular dynamics experiments. Results indicated that the mechanism of inhibition may be competitive, which agrees with previous binding experiments done with 6,10,2',6'-tetraacetyl-O-catalpol.
Asunto(s)
ADN Polimerasa Dirigida por ADN/química , Inhibidores Enzimáticos/química , Glucósidos Iridoides/química , Simulación de Dinámica Molecular , Inhibidores Enzimáticos/farmacología , Glucósidos Iridoides/farmacología , Ligandos , Inhibidores de la Síntesis del Ácido Nucleico , Unión Proteica , Conformación Proteica , SolucionesRESUMEN
Dehydroleucodine (DhL) is a sesquiterpene lactone of the guaianolide group with gastric cytoprotective activity. Recent studies have also demonstrated that DhL inhibits the proliferation of vascular smooth muscle cells. In this study we examined the effect of DhL in the differentiation of 3T3-L1 preadipocytes. The addition of DhL significantly inhibited the differentiation of 3T3-L1 preadipocytes along with a significant decrease in the accumulation of lipid content by a dramatic downregulation of the expression of adipogenic-specific transcriptional factors PPARγ and C-EBPα. However, phosphorylation of AMPKα, Erk1/2 and Akt1 was not inhibited by DhL treatment. Interestingly, we also found that 11,13-dihydrodehydroleucodine, a derivative of DhL with inactivated α-methylene-γ-lactone function, also inhibited the differentiation of 3T3-L1 preadipocytes. Taken together, these data suggest that DhL has an important inhibitory effect in cellular pathways regulating adipocyte differentiation by modulating the PPARγ expression, which is known to play a pivotal role during adipogenesis.
Asunto(s)
Adipocitos/citología , Adipocitos/efectos de los fármacos , Adipogénesis/efectos de los fármacos , Lactonas/farmacología , Sesquiterpenos/farmacología , Células 3T3-L1 , Adipocitos/metabolismo , Animales , Ratones , Factores de Transcripción/antagonistas & inhibidores , Factores de Transcripción/metabolismoRESUMEN
Coumarin metabolism by several Aspergillus strains was studied. Aspergillus ochraceus and Aspergillus niger carried out the reduction of the C3-C4 double bond to yield dihydrocoumarin in 24h. Meanwhile, the first strain did not transform dihydrocoumarin after 7d, A. niger demonstrated to have two divergent catabolic pathways: (a) the lactone moiety opening and further reduction of the carboxylic acid furnishing the primary alcohol 2-(3-hydroxypropyl)phenol and, (b) the hydroxylation of the aromatic ring of dihydrocoumarin at a specific position to give 6-hydroxy-3,4-dihydrochromen-2-one. Aspergillus flavus did not perform double bond reductions, and only produced oxygenated metabolites, mainly 5-hydroxycoumarin. Enzyme-specific inhibitors and a coumarin analogous were useful to confirm the A. niger catabolic route.