RESUMEN
Two prenylated flavonoid derivatives, 5-hydroxy-4'-methoxy-2",2"-dimethylpyrano-(7,8:6",5")flavanone (1) and 5,4'-dihydroxy-[2"-(1-hydroxy-1-methylethyl)dihydrofurano]-(7,8:5",4")flavanone (2), were isolated from an ethyl acetate-soluble extract of the leaves of Macaranga conifera using an in vitro activity-guided fractionation procedure based on the inhibition of cyclooxygenase-2. Also obtained were eight known compounds, 5,7-dihydroxy-4'-methoxy-8-(3-methylbut-2-enyl)flavanone (3), lonchocarpol A (4), sophoraflavanone B (5), 5,7-dihydroxy-4'-methoxy-8-(2-hydroxy-3-methylbut-3-enyl)flavanone (6), tomentosanol D (7), lupinifolinol (8), isolicoflavonol (9), and 20-epibryonolic acid (10). The structures of compounds 1 and 2 were determined using spectroscopic methods. All isolates were tested for their inhibitory effects against both cyclooxygenases-1 and -2, and selected compounds were evaluated in a mouse mammary organ culture assay.
Asunto(s)
Inhibidores de la Ciclooxigenasa/química , Inhibidores de la Ciclooxigenasa/farmacología , Euphorbiaceae/química , Flavonoides/química , Flavonoides/farmacología , Isoenzimas/antagonistas & inhibidores , Animales , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Fraccionamiento Químico/métodos , Ciclooxigenasa 1 , Ciclooxigenasa 2 , Inhibidores de la Ciclooxigenasa 2 , Inhibidores de la Ciclooxigenasa/aislamiento & purificación , Flavonoides/aislamiento & purificación , Concentración 50 Inhibidora , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Neoplasias Mamarias Experimentales/enzimología , Proteínas de la Membrana , Ratones , Ratones Endogámicos BALB C , Resonancia Magnética Nuclear Biomolecular , Técnicas de Cultivo de Órganos , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Hojas de la Planta/química , Prostaglandina-Endoperóxido Sintasas , Prenilación de ProteínaRESUMEN
A new bicyclic diarylheptanoid, rel-(3S,4aR,10bR)-8-hydroxy-3-(4-hydroxyphenyl)-9-methoxy-4a,5,6,10b-tetrahydro-3H-naphtho[2,1-b]pyran (1), as well as four known compounds, 1,2-dihydro-1,2,3-trihydroxy-9-(4-methoxyphenyl)phenalene (2), hydroxyanigorufone (3), 2-(4-hydroxyphenyl)naphthalic anhydride (4), and 1,7-bis(4-hydroxyphenyl)hepta-4(E),6(E)-dien-3-one (5), were isolated from an ethyl acetate-soluble fraction of the methanol extract of the fruits of Musa x paradisiaca cultivar, using a bioassay based on the induction of quinone reductase (QR) in cultured Hepa1c1c7 mouse hepatoma cells to monitor chromatographic fractionation. The structure and relative stereochemistry of compound 1 were elucidated unambiguously by one- and two-dimensional NMR experiments ((1)H NMR, (13)C NMR, DEPT, COSY, HMQC, HMBC, and NOESY) and single-crystal X-ray diffraction analysis. Isolates 1-5 were evaluated for their potential cancer chemopreventive properties utilizing an in vitro assay to determine quinone reductase induction and a mouse mammary organ culture assay.
Asunto(s)
Neoplasias Mamarias Experimentales/enzimología , Musa/química , NAD(P)H Deshidrogenasa (Quinona)/biosíntesis , Extractos Vegetales/farmacología , Animales , Carcinoma Hepatocelular/enzimología , Inducción Enzimática , Femenino , Neoplasias Hepáticas Experimentales/enzimología , Ratones , Ratones Endogámicos BALB C , Células Tumorales CultivadasRESUMEN
Activity-guided fractionation of the EtOAc-soluble extract of the whole plants of Sida acuta using a bioassay based on the induction of quinone reductase (QR) in cultured Hepa 1c1c7 mouse hepatoma cells, led to the isolation of ten active compounds of previously known structure, quindolinone (1), cryptolepinone (2), 11-methoxyquindoline (3), N-trans-feruloyltyramine (4), vomifoliol (5), loliolide (6), 4-ketopinoresinol (7), scopoletin (8), evofolin-A (9), and evofolin-B (10), along with five inactive compounds of known structure, ferulic acid, sinapic acid, syringic acid, (+/-)-syringaresinol, and vanillic acid. These isolates were identified by physical and spectral data measurement. A new derivative of quindolinone, 5,10-dimethylquindolin-11-one (1a) was synthesized and characterized spectroscopically. Of the active substances, compounds 1-3 and 1a exhibited the most potent QR activity, with observed CD (concentration required to double induction) values ranging from 0.01 to 0.12 microg/mL. Six compounds were then evaluated in a mouse mammary organ culture assay, with cryptolepinone (2), N-trans-feruloyltyramine (4), and 5,10-dimethylquindolin-11-one (1a) found to exhibit 83.3, 75.0, and 66.7% inhibition of 7,12-dimethylbenz[a]anthracene-induced preneoplastic lesions, respectively, at a dose of 10 microg/mL.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Transformación Celular Neoplásica/efectos de los fármacos , Malvaceae/química , Glándulas Mamarias Animales/efectos de los fármacos , NAD(P)H Deshidrogenasa (Quinona)/biosíntesis , 9,10-Dimetil-1,2-benzantraceno/toxicidad , Alternativas al Uso de Animales , Animales , Antineoplásicos Fitogénicos/química , Carcinoma Hepatocelular/enzimología , Carcinoma Hepatocelular/patología , Transformación Celular Neoplásica/inducido químicamente , Inducción Enzimática/efectos de los fármacos , Glándulas Mamarias Animales/citología , Ratones , Estructura Molecular , Técnicas de Cultivo de Órganos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Relación Estructura-Actividad , Células Tumorales CultivadasRESUMEN
The present study provides a correlation of the antimutagenic and chemopreventive activity of the barks of two commonly observed plants viz. Acacia auriculiformis and Acacia nilotica. We used the Ames antimutagenicity assay and the mouse mammary gland organ culture (MMOC) model. The plants were extracted with organic solvents to obtain chloroform fractions and acetone extracts. The antimutagenic activity was determined in two different strains using both direct-acting [4-nitro-o-phenylenediamine (NPD) or sodium azide] and indirect-acting [2-aminofluorene (2AF)] mutagens. The anticarcinogenic activity was evaluated based on the development of preneoplastic lesions in response to the chemical carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). The results showed that the activity resulting from the 2AF mutagen was selectively greater than the activity from the direct-acting mutagens. Moreover, in general, acetone extracts were more potent in suppressing mutagenesis than the chloroform extracts. The antimutagenicity results obtained with extracts using the 2AF--TA100 system were comparable to the chemopreventive results with DMBA-induced mammary lesions. The order of activity in both tests was A. nilotica > A. auriculiformis. These results exhibited a good correlation between the antimutagenesis assay and the MMOC model, suggesting that these plants may contain active chemopreventive agents.
Asunto(s)
Acacia , Antimutagênicos/farmacología , Antineoplásicos Fitogénicos/farmacología , Extractos Vegetales/farmacología , 9,10-Dimetil-1,2-benzantraceno/toxicidad , Animales , Antimutagênicos/uso terapéutico , Antineoplásicos Fitogénicos/uso terapéutico , Femenino , Fluorenos/toxicidad , Glándulas Mamarias Animales/efectos de los fármacos , Glándulas Mamarias Animales/patología , Ratones , Ratones Endogámicos BALB C , Mutágenos/toxicidad , Fenilendiaminas/toxicidad , Corteza de la Planta/química , Extractos Vegetales/uso terapéutico , Lesiones Precancerosas/inducido químicamente , Lesiones Precancerosas/prevención & control , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/genética , Azida Sódica/toxicidadRESUMEN
Fractionation of an ethyl acetate-soluble extract of the bark of Artocarpus dadah has led to the isolation of three new prenylated stilbenoid derivatives, 3-(gamma,gamma-dimethylallyl)resveratrol (1), 5-(gamma,gamma-dimethylallyl)oxyresveratrol (2), 3-(2,3-dihydroxy-3-methylbutyl)resveratrol (3), and a new benzofuran derivative, 3-(gamma,gamma-dimethylpropenyl)moracin M (4), along with six known compounds, oxyresveratrol, (+)-catechin, afzelechin-3-O-alpha-L-rhamnopyranoside, (-)-epiafzelechin, dihydromorin, and epiafzelechin-(4beta-->8)-epicatechin. From an ethyl acetate-soluble extract of the twigs of the same plant were isolated compound 4 and two new neolignan derivatives, dadahols A (5) and B (6), as well as 10 known compounds, oxyresveratrol, (+)-catechin, afzelechin-3-O-alpha-L-rhamnopyranoside, resveratrol, steppogenin, moracin M, isogemichalcone B, gemichalcone B, norartocarpetin, and engeletin. The structures of compounds 1-6 were determined using spectroscopic and chemical methods. Isolates were evaluated for their inhibitory effects against both cyclooxygenase-1 (COX-1) and -2 (COX-2) and in a mouse mammary organ culture assay.
Asunto(s)
Transformación Celular Neoplásica/efectos de los fármacos , Inhibidores de la Ciclooxigenasa/aislamiento & purificación , Moraceae/química , Plantas Medicinales/química , Estilbenos/aislamiento & purificación , 9,10-Dimetil-1,2-benzantraceno/farmacología , Acetilación , Animales , Benzofuranos/química , Benzofuranos/aislamiento & purificación , Benzofuranos/farmacología , Mama , Catequina , Cromatografía Líquida de Alta Presión , Cromatografía en Capa Delgada , Ciclooxigenasa 1 , Ciclooxigenasa 2 , Inhibidores de la Ciclooxigenasa 2 , Inhibidores de la Ciclooxigenasa/química , Inhibidores de la Ciclooxigenasa/farmacología , Modelos Animales de Enfermedad , Indonesia , Isoenzimas/antagonistas & inhibidores , Proteínas de la Membrana , Metilación , Ratones , Ratones Endogámicos BALB C , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Técnicas de Cultivo de Órganos , Corteza de la Planta/química , Extractos Vegetales , Brotes de la Planta/química , Prostaglandina-Endoperóxido Sintasas , Espectroscopía Infrarroja por Transformada de Fourier , Estereoisomerismo , Estilbenos/química , Estilbenos/farmacologíaRESUMEN
Activity-guided fractionation of an ethyl acetate extract of the aerial parts of Tithonia diversifolia, using an antiproliferation bioassay performed with human colon cancer (Col2) cells, led to the isolation of three new sesquiterpenoids, 2alpha-hydroxytirotundin (1), tithofolinolide (2), and 3alpha-acetoxydiversifolol (3), along with eight known sesquiterpene lactones, 3beta-acetoxy-8beta-isobutyryloxyreynosin (4), tagitinin C (5), 1beta,2alpha-epoxytagitinin C (6), 4alpha,10alpha-dihydroxy-3-oxo-8beta-isobutyryloxyguaia-11(13)-en-12,6alpha-olide (7), 3alpha-acetoxy-4alpha-hydroxy-11(13)-eudesmen-12-oic acid methyl ester, 17,20-dihydroxygeranylnerol, tagitinin A, and tirotundin. These isolates were evaluated for their potential as cancer chemopreventive agents, by measuring antiproliferative activity in Col2 cells and induction of cellular differentiation in human promyelocytic leukemia (HL-60) cells. Selected compounds were then investigated for their ability to inhibit 7,12-dimethylbenz[a]anthracene-induced preneoplastic lesions in a mouse mammary organ culture assay. Among these isolates, 5 and 6 showed significant antiproliferative activity, 2, 4, and 7 induced HL-60 cellular differentiation, and 4 significantly inhibited (63.0% at 10 microg/mL) lesion formation in the mouse mammary organ culture assay. The chemical structures of 1-3 were elucidated by spectroscopic analysis. The absolute configurations of 1 and 2 were determined by Mosher ester methodology.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Asteraceae/química , Lactonas/aislamiento & purificación , Plantas Medicinales/química , Sesquiterpenos/aislamiento & purificación , Animales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Benzo(a)Antracenos/farmacología , Cromatografía Líquida de Alta Presión , Humanos , Lactonas/química , Lactonas/farmacología , Leucemia Mieloide , Neoplasias Mamarias Experimentales/inducido químicamente , Ratones , Ratones Endogámicos BALB C , Conformación Molecular , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Puerto Rico , Sesquiterpenos/química , Sesquiterpenos/farmacologíaRESUMEN
A new butenylflavanone, (2S)-5-hydroxy-7-methoxy-8-[(E)-3-oxo-1-butenyl]flavanone (1), and a new rotenoid, 4',5'-dihydro-11,5'-dihydroxy-4'-methoxytephrosin (2), as well as three active flavonoids of previously known structure, isoliquiritigenin (3), genistein (4), and chrysoeriol (5), along with nine known inactive compounds, alpha-toxicarol (6), sumatrol, 6a,12a-dehydro-alpha-toxicarol, 11-hydroxytephrosin, obovatin, marmesin, lupenone, benzyl benzoate, and benzyl trans-cinnamate, were isolated from an ethyl acetate-soluble extract of the stems of Tephrosia toxicaria, using a bioassay based on the induction of quinone reductase (QR) in cultured Hepa 1c1c7 mouse hepatoma cells to monitor chromatographic fractionation. The structures of compounds 1 and 2 were elucidated by spectroscopic data interpretation. All isolates were evaluated for their potential cancer chemopreventive properties utilizing an in vitro assay to determine quinone reductase induction. Selected compounds were tested in a mouse mammary organ culture assay to evaluate the inhibition of 7,12-dimethylbenz[a]anthracene (DMBA)-induced preneoplastic lesions.
Asunto(s)
Anticarcinógenos/aislamiento & purificación , Cromonas/aislamiento & purificación , Flavonoides/aislamiento & purificación , Compuestos Heterocíclicos de 4 o más Anillos/aislamiento & purificación , Plantas Medicinales/química , Tephrosia/química , Animales , Anticarcinógenos/química , Anticarcinógenos/farmacología , Carcinoma Hepatocelular , Cromonas/química , Cromonas/farmacología , Flavonoides/química , Flavonoides/farmacología , Compuestos Heterocíclicos de 4 o más Anillos/química , Compuestos Heterocíclicos de 4 o más Anillos/farmacología , Neoplasias Mamarias Experimentales , Ratones , Estructura Molecular , NAD(P)H Deshidrogenasa (Quinona)/metabolismo , Perú , Tallos de la Planta/química , Estereoisomerismo , Células Tumorales Cultivadas/efectos de los fármacosRESUMEN
A new cassane diterpene, dipteryxic acid (1), and a new isoflavonolignan, 5-methoxyxanthocercin A (2), as well as four known active compounds, isoliquiritigenin (3), 6,4'-dihydroxy-3'-methoxyaurone (4), sulfuretin (5), and (+/-)-balanophonin (6), and five known inactive compounds, butin, eriodictyol, 7-hydroxychromone, 7,3'-dihydroxy-8,4'-dimethoxyisoflavone, and (-)-lariciresinol, were isolated from an ethyl acetate-soluble extract of the seeds of Dipteryx odorata, using a bioassay based on the induction of quinone reductase (QR) in cultured Hepa 1c1c7 mouse hepatoma cells to monitor chromatographic fractionation. The structures of compounds 1 and 2 were elucidated by spectroscopic data interpretation. Single-crystal X-ray diffraction analysis was used to confirm the relative stereochemistry of compound 1. Selected compounds (3-5) were evaluated in a mouse mammary organ culture assay, with isoliquiritigenin (3) found to exhibit 76% inhibition at a dose of 10 microg/mL.