RESUMEN
OBJECTIVES: Based upon reported ethnomedicinal use by Native Americans, extracts and pure isolates from leaves and seeds of Magnolia grandiflora, M. virginiana, M. acuminata and M. macrophylla, all native to the Southeastern United States, were investigated for their anti-inflammatory potential against cyclooxygenase 2 (COX-2). MATERIAL AND METHODS: The extracts and pure compounds from Magnolia species were tested for their production of prostaglandin E(2) (PGE(2)) using a mouse macrophage (RAW 264.7) assay where cells were stimulated by lipopolysaccharide. RESULTS: Leaf extracts were moderately active (44-58% inhibition at 50 microg/ml) whereas seed extracts showed significant activity of 54-88% inhibition, respectively. In the seed extract of M. grandiflora, honokiol, magnolol and 4'-O-methylhonokiol strongly inhibited COX-2 (IC(50): 1.2-2.0 microg/ml), 3-O-methylmagnolol was moderately active while a new compound was inactive towards COX-2. The neolignans were not cytotoxic to macrophages (RAW 264.7) and kidney fibroblast (VERO) cells in vitro. CONCLUSIONS: The results indicate that the reported ethnomedicinal use of the investigated Magnolia species is in agreement with anti-inflammatory activity of their respective compounds.
Asunto(s)
Inhibidores de la Ciclooxigenasa 2/farmacología , Lignanos/farmacología , Magnolia/química , Extractos Vegetales/farmacología , Animales , Supervivencia Celular/efectos de los fármacos , Chlorocebus aethiops , Inhibidores de la Ciclooxigenasa 2/efectos adversos , Inhibidores de la Ciclooxigenasa 2/aislamiento & purificación , Dinoprostona/biosíntesis , Fibroblastos/efectos de los fármacos , Fibroblastos/enzimología , Lignanos/aislamiento & purificación , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/enzimología , Magnolia/crecimiento & desarrollo , Ratones , Estructura Molecular , América del Norte , Extractos Vegetales/efectos adversos , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta/química , Semillas/química , Células VeroRESUMEN
Sesquiterpene lactones possess a variety of biological activities, including anti-inflammatory activity. Two plants native to the southeastern United States, Magnolia grandiflora (L.) and Smallanthus uvedalius (L.) [syn Polymnia uvedalius (L.)], are novel sources of the sesquiterpene lactones parthenolide and enhydrin, respectively. In this study, the anti-inflammatory and anti-hyperalgesic effects of these isolated lactones from these two plant sources were evaluated in the rat carrageenan inflammation model. Rats received ip injections of either vehicle (propylene glycol), indomethacin (5 mg/kg), 11,13-dihydroparthenolide (20 mg/kg), parthenolide (5 or 20 mg/kg) or enhydrin (5 or 20 mg/kg). A 100-microl injection of 2.0% carrageenan was made into the plantar surface of the right hindpaw. Paw withdrawal latencies and paw volumes in both inflamed and non-inflamed paws were recorded at four test intervals: pre-inflammation baseline (0 time point), and 1, 2 and 4 h post-carrageenan injection. Vehicle-treated animals exhibited a significant time-dependent hyperalgesic and edema response that was greatest at the 4-h test interval. Indomethacin significantly blocked the hyperalgesic response and modestly attenuated the edema response. Parthenolide (20 mg/kg) and enhydrin (20 mg/kg) significantly blocked the hyperalgesic response and significantly attenuated the edema response; 11,13-dihydroparthenolide did not affect either inflammation or hyperalgesia. These findings suggest that parthenolide and enhydrin from these plant sources may be useful in the treatment of inflammatory pain.
Asunto(s)
Analgésicos no Narcóticos/aislamiento & purificación , Analgésicos no Narcóticos/farmacología , Antiinflamatorios no Esteroideos/aislamiento & purificación , Antiinflamatorios no Esteroideos/farmacología , Asteraceae/química , Magnolia/química , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos/farmacología , Analgésicos no Narcóticos/química , Animales , Antiinflamatorios no Esteroideos/química , Carragenina , Indometacina/farmacología , Inflamación/tratamiento farmacológico , Inflamación/etiología , Lactonas/química , Lactonas/aislamiento & purificación , Lactonas/farmacología , Masculino , Estructura Molecular , Ratas , Ratas Sprague-Dawley , Sesquiterpenos/químicaRESUMEN
Abstract. Tuberculosis (TB), mainly caused by Mycobacterium tuberculosis, is the leading killer among all infectious diseases worldwide and is responsible for more than two million deaths annually. For over thirty years no antitubercular agents with new mechanisms of action have been developed. The recent increase in the number of multi-drug resistant clinical isolates of M. tuberculosis has created an urgent need for the discovery and development of new antituberculosis leads. This review covers recent reports on plant-derived terpenoids that have demonstrated moderate to high activity in in vitro bioassays against M. tuberculosis. In this review, mono-, sesqui-, di- and triterpenes, and sterols, their structural analogs and semisynthetic derivatives will be discussed, with particular emphasis on the structural features essential for antimycobacterial activity.
Asunto(s)
Antituberculosos/uso terapéutico , Fitoterapia , Preparaciones de Plantas/uso terapéutico , Terpenos/uso terapéutico , Tuberculosis/tratamiento farmacológico , Antituberculosos/química , Cycadopsida , Humanos , Magnoliopsida , Mycobacterium tuberculosis/efectos de los fármacos , Preparaciones de Plantas/química , Esteroles/química , Esteroles/aislamiento & purificación , Esteroles/uso terapéutico , Relación Estructura-Actividad , Terpenos/química , Terpenos/aislamiento & purificaciónRESUMEN
The chloroform solvate of uncarine C (pteropodine), (1'S,3R,4'aS,5'aS,10'aS)-1,2,5',5'a,7',8',10',10'a-octahydro-1'-methyl-2-oxospiro[3H-indole-3,6'(4'aH)-[1H]pyrano[3,4-f]indolizine]-4'-carboxylic acid methyl ester, C(21)H(24)N(2)O(4).CHCl(3), has an absolute configuration with the spiro C atom in the R configuration. Its epimer at the spiro C atom, uncarine E (isopteropodine), (1'S,3S,4'aS,5'aS,10'aS)-1,2,5',5'a,7',8',10',10'a-octahydro-1'-methyl-2-oxospiro[3H-indole-3,6'(4'aH)-[1H]pyrano[3,4-f]indolizine]-4'-carboxylic acid methyl ester, C(21)H(24)N(2)O(4), has Z' = 3, with no solvent. Both form intermolecular hydrogen bonds involving only the oxindole, with N.O distances in the range 2.759 (4)-2.894 (5) A.
Asunto(s)
Alcaloides/química , Indoles/química , Plantas Medicinales/química , Compuestos de Espiro/química , Cristalografía por Rayos X , Modelos Moleculares , Estructura Molecular , Oxindoles , EstereoisomerismoRESUMEN
In Asia and North America, members of the family Magnoliaceae have been and are presently used extensively in indigenous herbal medicine. Many taxa of the genus Magnolia produce lignans and sesquiterpene lactones, some with considerable in vitro bioactivities. This review focuses on selected natural products of the genus Magnolia from the southeastern United States with demonstrated biological and pharmacological properties. Ethnomedicinal data obtained from the Native Americans of the southeastern United States correlate well with the results of pharmacological investigations.
RESUMEN
Eight dibenzocyclooctadiene-type lignans, pyramidatin A-H, were isolated from the leaves of Magnolia pyramidata. Their structures were established by spectral methods, mainly 2D NMR spectroscopic techniques, which involved combined applications of COSY, DEPT. 1H, 13C correlations, COLOC, INAPT and long-range inverse 1H, 13C NMR correlations. The molecular structures of pyramidatin A and B were determined by single crystal X-ray diffraction. The absolute configurations of all eight lignans were derived from CD spectral correlations with structurally related dibenzocyclooctadienes of known absolute configuration.
Asunto(s)
Lignanos/aislamiento & purificación , Magnoliopsida/química , Dicroismo Circular , Cristalografía por Rayos X , Lignanos/química , Espectroscopía de Resonancia Magnética , Conformación MolecularRESUMEN
The antioxidant activity of a series of flavonoids against peroxyl radicals generated from thermal homolysis of 2, 2'-azobis-amidinopropane was determined by the Total Oxyradical Scavenging Capacity (TOSC) assay. Seven flavonoids with hydroxy and/or methoxy substitution were analyzed and compared to the water-soluble vitamin E analogue Trolox. The most active compound was the flavonol quercetin, followed by its 3-glycoside derivative rutin; these were 7 and 5 times, respectively, better scavengers of peroxyl radical than Trolox. Among the flavones with both hydroxy and methoxy substitution, the most active against peroxyl radicals was the 5,6,4'-trihydroxy-7,8,3'-trimethoxyflavone (thymonin), with a TOSC value 1.5 times greater than that of Trolox. The activity of the remaining flavones was in the following relative order: 5, 4'-dihydroxy-6,7,8,3'-tetramethoxyflavone > 5-hydroxy-3,6,7,3', 4'-pentamethoxyflavone (artemetin) > 5,4'-dihydroxy-3,6, 7-trimethoxyflavone > 5,6,7,8,2',3',4',5'-octamethoxyflavone (agehoustin A). The data suggest a potential role for dietary intake of flavonoid-containing foods in lowering the risk of certain pathophysiologies that have been associated with free-radical-mediated events.
Asunto(s)
Flavonoides/farmacología , Peróxidos , Flavonoides/química , Relación Estructura-ActividadRESUMEN
In a bioassay guided search for antimycobacterial compounds from higher plants, the root extracts of Elecampane (Inula helenium L.; Asteraceae) and Sweet Coneflower (Rudbeckia subtomentosa Pursh.; Asteraceae) were chemically investigated for their active constituents. Chromatographic fractions of root extracts of l. helenium, which exhibited significant activity against Mycobacterium tuberculosis, provided the known eudesmanolides alantolactone, isoalantolactone, and 11 alpha H, 13-dihydroisoalantolactone. Peracid epoxidation of alantolactone and isoalantolactone provided 5 alpha-epoxyalantolactone and 4(15) alpha-epoxyisoalantolactone, respectively and oxidation of alantolactone with OsO4 gave 11,13-dihydroxyalantolactone. Active fractions from R subtomentosa contained the known alloalantolactone and 3-oxoalloalantolactone. The structures of the above compounds were established by spectroscopic methods including 1D and 2D NMR techniques as well as spectral comparison with previously reported data. The molecular structure of 5 alpha-epoxyalantolactone was determined by single crystal X-ray diffraction. Eleven natural and semisynthetic eudesmanolides were tested in a radiorespirometric bioassay for activity against M. tuberculosis. 5 alpha-Epoxyalantolactone and encelin from Montanoa speciosa showed minimum inhibitory concentrations (MICs) of 8 and 16 micrograms ml-1, respectively. Alantolactone, isoalantolactone and its 4 alpha, 15-epoxide, 1,2-dehydro-3-epi-isotelekin and alloalantolactone gave MICs of 32 micrograms ml-1. All other compounds showed MIC values of 128 micrograms ml-1 or higher.
Asunto(s)
Antituberculosos/aislamiento & purificación , Inula/química , Mycobacterium tuberculosis/efectos de los fármacos , Sesquiterpenos/aislamiento & purificación , Antituberculosos/química , Antituberculosos/farmacología , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Sesquiterpenos/química , Sesquiterpenos/farmacología , Relación Estructura-ActividadRESUMEN
In a bioassay-guided search for antimycobacterial compounds from higher plants, we have chemically investigated methanolic extracts of seeds of Melia volkensii. Chromatographic fractions provided two new euphane (20R)-type triterpenoids. The structures of the new compounds, 12beta-hydroxykulactone (1) and 6beta-hydroxykulactone (2), were elucidated by 1D and 2D NMR (13C, 1H, 1H-1H COSY, HMQC, HMBC, and NOESY spectra) and FABMS studies and shown to be hydroxyl derivatives of kulactone (3). Also isolated was the known kulonate (4). In a radiorespirometric bioassay against Mycobacterium tuberculosis, compounds 1, 2, and 4 exhibited minimum inhibitory concentrations of 16, 4, and 16 microg/mL, respectively.
Asunto(s)
Antituberculosos/farmacología , Lactonas/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Plantas Medicinales/química , Antituberculosos/aislamiento & purificación , Cromatografía Líquida de Alta Presión , Kenia , Lactonas/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Metanol , Mycobacterium tuberculosis/metabolismo , Oxígeno/metabolismo , Semillas/química , Espectrofotometría UltravioletaRESUMEN
In a bioassay-guided search for antimycobacterial natural products from higher plants, we have chemically investigated the methanol extract of aerial parts of Ajuga remota Benth. (Labiatae) for its active constituent(s). Bioactive chromatographic fractions of the crude extract provided the known triterpene ergosterol-5,8-endoperoxide plus the diterpenes clerodin, ajugarin-I, and ajugarin-II, which had been previously isolated from A. remota. This is the first report on the isolation of ergosterol-5,8-endoperoxide from this plant. The above compounds were tested in a radiorespirometric bioassay for activity against Mycobacterium tuberculosis. Ergosterol-5,8-endoperoxide showed a minimum inhibitory concentration (MIC) of 1 microgram/ml, while ergosterol-5,8-endoperoxide acetate, ergosterol, and ergosta-5,7,9(11),22-tetraen-3 beta-ol gave MICs of 8 micrograms/ml, > 128 micrograms/ml, and 128 micrograms/ml, respectively. Clerodin, ajugarin-I, and ajugarin-II were inactive with MICs of > 128 micrograms/ml.
Asunto(s)
Antituberculosos/farmacología , Ergosterol/análogos & derivados , Mycobacterium tuberculosis/efectos de los fármacos , Extractos Vegetales/farmacología , Plantas/química , Antituberculosos/química , Antituberculosos/aislamiento & purificación , Cristalografía por Rayos X , Ergosterol/química , Ergosterol/aislamiento & purificación , Ergosterol/farmacología , Pruebas de Sensibilidad Microbiana , Estructura MolecularRESUMEN
The title triterpene, D-friedoolean-14-en-3 beta-yl acetate, C32H52O2, was isolated from dichloromethane extracts of the roots of common ragweed Ambrosia artemisiifolia. The skeleton contains five fused six-membered rings with an average Csp3-Csp3 bond distance of 1.549 (6) A and one double bond of length 1.348 (6) A. The D and E rings are cis-fused. The compound also contains a beta-oriented acetate group with a C-O distance 1.461 (5) A.
Asunto(s)
Ácido Oleanólico/análogos & derivados , Raíces de Plantas/química , Triterpenos/química , Cristalografía por Rayos X , Modelos Moleculares , Conformación Molecular , Ácido Oleanólico/química , Extractos Vegetales/químicaRESUMEN
Six matricaria esters (MEs) and two matricaria lactones (MLs), isolated from members of the tribe Astereae (Asteraceae), were tested against Mycobacterium tuberculosis and M. avium, using a radiorespirometric bioassay. (2Z,8Z)-ME and (2E-8Z)-ME gave minimum inhibitory concentrations (MICs) of 50 micrograms ml-1 against M. tuberculosis and respective MICs of 25 and 50 micrograms ml-1 against M. avium. The (4Z,8Z)-ML, (2Z)-8-dehydro-ME and (2Z,8Z)-10-angeloyloxy-(2Z,8Z)-ME showed respective MICs of 12.5, 25, 25 micrograms ml-1 against M. tuberculosis and MICs of 50, 25, 25 micrograms ml-1 against M. avium, respectively. The MICs of (2Z,8Z)-10-tigloyloxy-ME and (2E,8Z)-10-angeloyloxy-ME and (4E,8Z)-ML ranged from 50 to > 100 micrograms ml-1 against both pathogenic mycobacteria.
Asunto(s)
Antituberculosos/aislamiento & purificación , Asteraceae/química , Complejo Mycobacterium avium/efectos de los fármacos , Mycobacterium tuberculosis/efectos de los fármacos , Antituberculosos/química , Antituberculosos/farmacología , Ésteres , Lactonas , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Estructura MolecularRESUMEN
In an attempt to study the structural dependence of antimycobacterial activity of the guaianolide dehydrocostus lactone and its derivatives, m-chloroperoxybenzoic acid oxidations of dehydrocostus lactone (1a) were performed. Three new monoepoxides, one previously synthesized diepoxide, and two new diepoxides were obtained. Two of the monoepoxides are C-10 epimers (3a, 3b), while the 4(15)-monoepoxide (2) has the 4alpha-O-configuration. The known diepoxide (4a) contains a C-10 alpha-epoxide and a beta-epoxide at C-4. The diepoxides 4b and 4c, each with a C-4 alpha-epoxy group, differ in the configuration of the epoxide ring at C-10. Allylic oxidation of dehydrocostus lactone (1a) with selenium dioxide/tert-butyl hydroperoxide afforded the known 3-epizaluzanin C (1b). The relative configurations of compounds 1b-4c were established by 1D and 2D NMR techniques (1H, 13C, COSY, NOESY, HMQC, and HMBC) as well as comparison with literature data. The molecular structures of lactones 1b, 4a, and 4c were determined by single-crystal X-ray diffraction. In radiorespirometric bioassays against Mycobacterium tuberculosis and Mycobacterium avium, dehydrocostus lactone (1a) exhibited minimum inhibitory concentrations of 2 and 16 microgram/mL, respectively. In contrast, its monoepoxides (2, 3a, and 3b) and diepoxides (4a-c), as well as its hydrogenated derivatives and other analogues (1b, 1c, 5, and 6), showed significantly lower activities against M. tuberculosis.
Asunto(s)
Antituberculosos/farmacología , Lactonas/farmacología , Mycobacterium/efectos de los fármacos , Sesquiterpenos/farmacología , Antituberculosos/metabolismo , Asteraceae/química , Lactonas/metabolismo , Pruebas de Sensibilidad Microbiana , Mycobacterium avium/efectos de los fármacos , Mycobacterium tuberculosis/efectos de los fármacos , Oxidación-Reducción , Sesquiterpenos/metabolismo , Relación Estructura-ActividadRESUMEN
The minimum inhibitory concentrations (MIC) against Mycobacterium tuberculosis and M. avium of parthenolide, costunolide, 1 (10)-epoxycostunolide and other germacranolide-type sesquiterpene lactones and derivatives were determined by use of a radiorespirometric bioassay. Structure-activity relationship studies with natural and semisynthetic sesquiterpene lactones suggested that the alpha-methylene-gamma-lactone moiety is an essential, but not sufficient, structural requirement for significant in vitro activity against M. tuberculosis and M. avium.
Asunto(s)
Antibacterianos/farmacología , Mycobacterium avium/efectos de los fármacos , Mycobacterium tuberculosis/efectos de los fármacos , Sesquiterpenos/farmacología , Pruebas de Sensibilidad MicrobianaRESUMEN
The crude methanol extract of the Kenyan shrub Leucas volkensii Gürke (Labiatae) displayed in a radiorespirometric bioassay antimycobacterial activity against Mycobacterium tuberculosis. Bioassay-guided fractionation of the crude extract led to the identification of (E)-phytol as the principal active component with a minimum inhibitory concentration (MIC) of 2 micrograms/ml, a value also observed for (3R,S,7R,11R)-phytanol, (Z)-phytol, and a commercially available 2:1 mixture of (E)- and (Z)-phytol. The derivatives (E)-phytol acetate, a mixture of the (2S,3S)- and (2R,3R)-isomers of (E)-phytol epoxide and (3R,S,7R,11R)-phytanic acid displayed lower activities with MICs of 8, 16, and > 128 micrograms/ml, respectively. Geraniol and farnesol, displayed MICs of 64 and 8 micrograms/ml, respectively. The activities of (E)-phytol, (Z)-phytol and (3R,S,7R,11R)-phytanol were found to be in the same range as ethambutol, a clinically useful drug with an MIC in the range 0.95-3.8 micrograms/ml.
Asunto(s)
Antituberculosos/farmacología , Fitol/farmacología , Antituberculosos/química , Antituberculosos/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis/efectos de los fármacos , Fitol/química , Fitol/aislamiento & purificación , Plantas Medicinales/química , Relación Estructura-ActividadRESUMEN
Two-hundred and thirty crude organic extracts from 118 plant species distributed among 10 families were evaluated for anti-mycobacterial activity. Activity was determined against Mycobacterium tuberculosis H(37)Rv and Mycobacterium avium using the BACTEC 460 radiorespirometric assay. At 100 µg/ml, twenty-four and ten of the extracts caused more than 95% inhibition of growth of M. tuberculosis and M. avium, respectively. The most active plant species (100% inhibition) were Borrichia frutescens, Solidago arguta, and Inula helenium against M. tuberculosis, Euthamia leptocephala against M. avium, and Erigeron strigosus and Magnolia acuminata against both mycobacteria.
RESUMEN
In a bioassay-guided search for antimycobacterial compounds from higher plants of the southeastern United States, we have chemically investigated the sea daisy (Borrichia frutescens) from coastal marshes of Louisiana for their active constituents. Bioactive chromatographic fractions provided two new triterpenes, (24R)-24,25-epoxycycloartan-3-one (1) and (23R)-3-oxolanosta-8,24-dien-23-ol (4), and (3 alpha H, 24R)-24,25-epoxycycloartan-3-ol (3a). Compound 3a had been previously isolated as a mixture of C-24 epimers. The structures of 1, 3a, and 4 were established by spectroscopic methods and chemical transformations, and the molecular structures of 1 and 4 were determined by single-crystal X-ray diffraction. In a radiorespirometric bioassay against Mycobacterium tuberculosis, the epoxycycloartanes 1 and 3a exhibited minimum inhibitory concentrations of 8 micrograms/mL. In contrast, the lanostadiene-type triterpene 4 showed no significant inhibition at 128 micrograms/mL, as did the acetate 3b. Cytotoxicity for Vero cells gave IC50 values of 71.8, 39.8, and 103.6 micrograms/mL for triterpenes 1, 3a, and 4, respectively.
Asunto(s)
Antituberculosos/aislamiento & purificación , Antituberculosos/farmacología , Mycobacterium/efectos de los fármacos , Plantas/química , Triterpenos/farmacología , Acetilación , Animales , Antineoplásicos Fitogénicos/farmacología , Chlorocebus aethiops , Cristalografía por Rayos X , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Hojas de la Planta/química , Tallos de la Planta/química , Espectrofotometría Infrarroja , Triterpenos/aislamiento & purificación , Células VeroRESUMEN
In our previous studies (Refs. 1 and 2), it was shown that protein tyrosine kinase (PTK) inhibitors, radicicol and herbimycin A, inhibit the expression of the mitogen-inducible cyclooxygenase (COX-2) and proinflammatory cytokines. Radicicol and herbimycin A possess polarized double bonds which can conjugate sulphydryl groups of proteins. Parthenolide, the predominant sesquiterpene lactone in European feverfew (Tanacetum parthenium), contains alpha-methylene-gamma-lactone (MGL) and an epoxide in its structure. These moieties can interact with biological nucleophiles such as a sulfhydryl group. Parthenolide inhibited the expression of COX-2 and proinflammatory cytokines (TNF alpha and IL-1) in lipopolysaccharide (LPS)-stimulated macrophages. The structure-function relationship indicates that the MGL moiety confers the inhibitory effect. Parthenolide suppressed LPS-stimulated protein tyrosine phosphorylation in the murine macrophage cell line (RAW 264.7). This suppression was correlated with its inhibitory effect on the expression of COX-2 and the cytokines. Among tyrosine phosphorylated proteins, mitogen-activated protein kinases (MAPKs) exhibited the most dramatic inhibition.
Asunto(s)
Proteínas Quinasas Dependientes de Calcio-Calmodulina/antagonistas & inhibidores , Citocinas/biosíntesis , Expresión Génica/efectos de los fármacos , Isoenzimas/biosíntesis , Macrófagos Alveolares/enzimología , Macrófagos Alveolares/inmunología , Proteínas Quinasas Activadas por Mitógenos , Prostaglandina-Endoperóxido Sintasas/biosíntesis , Sesquiterpenos/farmacología , Animales , Proteínas Quinasas Dependientes de Calcio-Calmodulina/metabolismo , Línea Celular , Ciclooxigenasa 2 , Inducción Enzimática , Inhibidores Enzimáticos/farmacología , Interleucina-1/biosíntesis , Proteínas Quinasas JNK Activadas por Mitógenos , Lipopolisacáridos/farmacología , Macrófagos , Macrófagos Alveolares/efectos de los fármacos , Masculino , Ratones , Estructura Molecular , Plantas Medicinales , Ratas , Ratas Sprague-Dawley , Relación Estructura-Actividad , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
Investigation of the roots and aerial parts of Solidago rugosa afforded the known diterpenes kolavenol, hardwickiic acid, (-)-kaur-16-en-19-oic acid, (+)-manool, (+)-3 beta-hydroxymanool, manoyl oxide and ent-abietic acid. In addition, the new labdane diterpene (+)-18-tigloyloxymanool and four new ent-abietanes were obtained. The structures of all known and new compounds were elucidated by spectroscopic methods, especially high-field 1H and 13C NMR, and inverse 1H-13C-correlation techniques, as well as chemical transformations. Six diterpenes were tested against Mycobacterium tuberculosis and M. avium, but showed no significant activities with minimum inhibitory concentrations of > 100 micrograms ml-1.