RESUMEN
Sixteen diterpenes (1-16), along with 10 previously described compounds, including four flavonoids and six diterpenes, were isolated from the aerial parts of Psiadia punctulata growing in Saudi Arabia. The diterpene structures were elucidated using NMR spectroscopy and mass spectrometry data. Furthermore, a DFT/NMR procedure was used to suggest the relative configuration of several compounds. The labdane-derived skeletons, namely, ent-atisane, ent-beyerene, ent-trachylobane, and ent-kaurene, were identified. The extracts, fractions, and pure compounds were then tested against Staphylococcus aureus, Streptococcus mutans, Treponema denticola, and Lactobacillus plantarum. One diterpenoid, namely, psiadin, showed an additive effect with the antiseptic chlorhexidine, with a fractional inhibitory concentration index of less than 1. Additionally, psiadin showed a prospective inhibition activity for bacterial efflux pumps.
Asunto(s)
Antiinfecciosos , Asteraceae , Diterpenos , Asteraceae/química , Diterpenos/química , Estructura Molecular , Estudios ProspectivosRESUMEN
Abietane diterpenoids, containing a quinone moiety, are synthesized in the roots of several Salvia species. Promising cytotoxicity and antiproliferative activities have been reported for these compounds in various cell and animal models. We have recently shown that aethiopinone, an o-naphto-quinone diterpene, produced in the roots of different Salvia species, is selectively cytotoxic against the A375 melanoma cell line. To enhance the synthesis of this abietane diterpenoid, we have engineered the plastidial 2-C-methyl-D-erythritol 4-phosphate-derived isoprenoid pathway in Salvia sclarea hairy roots by ectopic expression and plastid targeting of cyanobacterial genes encoding the 1-deoxy-D-xylulose 5-phosphate synthase or 1-deoxy-D-xylulose-5-phosphate reductoisomerase gene, the first two enzymatic steps of the plastidial MEP pathway, from which plant diterpenes primarily derive. Plastid-targeted expression of 1-deoxy-D-xylulose 5-phosphate synthase and 1-deoxy-D-xylulose-5-phosphate reductoisomerase proteins significantly enhanced the yield of aethiopinone by a 3-fold and about 6-fold increase, respectively. The accumulation of other abietane-type diterpenes (ferruginol, salvipisone, and carnosic acid), with interesting antiproliferative activity, was also increased. Compared to our previous data obtained by overexpressing the plant orthologous 1-deoxy-D-xylulose 5-phosphate synthase and 1-deoxy-D-xylulose-5-phosphate reductoisomerase genes in S. sclarea hairy roots, the results presented here confirm that the bacterial 1-deoxy-D-xylulose-5-phosphate reductoisomerase enzyme plays a major role than the DXS enzyme in the biosynthetic pathway of this class of compounds and that its ectopic expression does not conflict with active hairy root growth, resulting in a balanced trade-off between the transgenic hairy root final biomass and the increased content of o-naphto-quinone diterpenes, with interesting biological activities.
Asunto(s)
Abietanos/metabolismo , Cianobacterias/genética , Genes Bacterianos/genética , Raíces de Plantas/metabolismo , Salvia/metabolismo , Abietanos/análisis , Western Blotting , Regulación de la Expresión Génica de las Plantas , Raíces de Plantas/química , Raíces de Plantas/genética , Plantas Modificadas Genéticamente , Reacción en Cadena de la Polimerasa , Salvia/química , Salvia/genéticaRESUMEN
The identification of inhibitors of Hsp90 is currently a primary goal in the development of more effective drugs for the treatment of various types of multidrug resistant malignancies. In an attempt to identify new small molecules modulating the activity of Hsp90, we screened a small library of tetranortriterpenes. A high-affinity interaction with Hsp90 inducible form was uncovered for eight of these compounds, five of which are described here for the first time. By monitoring the ATPase activity and the citrate synthase thermal induced aggregation, compound 1 (cedrelosin A), 3 (7α-limonylacetate), and 5 (cedrelosin B), containing a limonol moiety, were found to be the most effective in compromising the Hsp90α chaperone activity. Consistent with these findings, the three compounds caused a depletion of c-Raf and pAkt Hsp90 client proteins in HeLa and MCF/7 cell lines. Induced fit docking protocol and molecular dynamics were used to rationalize the structural basis of the biological activity of the limonol derivatives. Taken together, these results point to limonol-derivatives as promising scaffolds for the design of novel Hsp90α inhibitors.
Asunto(s)
Antineoplásicos/química , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Extractos Vegetales/química , Triterpenos/química , Adenosina Trifosfatasas/metabolismo , Antineoplásicos/farmacología , Sitios de Unión , Supervivencia Celular , Chromolaena/química , Citrato (si)-Sintasa/metabolismo , Ensayos de Selección de Medicamentos Antitumorales/métodos , Células HeLa , Humanos , Células MCF-7 , Simulación del Acoplamiento Molecular , Hojas de la Planta/química , Unión Proteica , Conformación Proteica , Pliegue de Proteína , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/farmacología , Triterpenos/farmacologíaRESUMEN
Eight new limonoids (1-8) and one new phenol glycoside (9), along with six known compounds, were isolated from the leaves of Azaridachta indica. The structures of 1-9 were elucidated on the basis of spectroscopic data analysis. Compounds isolated were assayed for their cytotoxicity against different cancer cell lines. Moreover, their ability to interact with the molecular chaperone Hsp90, affecting its biological activity, was tested.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Azadirachta/química , Limoninas/aislamiento & purificación , Limoninas/farmacología , Antineoplásicos Fitogénicos/química , Ensayos de Selección de Medicamentos Antitumorales , Proteínas HSP90 de Choque Térmico/metabolismo , Células HeLa , Humanos , Limoninas/química , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Hojas de la Planta/química , VenezuelaRESUMEN
Two new compounds, 5-methyl-2-(2-methylbutanoyl)phloroglucinol 1-O-(6-O-ß-D-apiofuranosyl)-ß-D-glucopyranoside (1) and trans-2,3-dihydrokaempferol 3-O-(4-O-sulfo)-α-L-arabinopyranoside (2), together with 14 known flavonoids, trans-dihydrokaempferol 3-O-α-L-arabinopyranoside (3), trans-taxifolin 3-O-α-L-arabinofuranoside (4), quercetin 3-O-α-L-rhamnopyranoside (5), quercetin 3'-O-α-L-arabinofuranoside (6), catechin 3-O-α-L-rhamnopyranoside (7), trans-taxifolin 3-O-α-L-arabinopyranoside (8), cis-dihydrokaempferol 3-O-α-L-arabinopyranoside (9), catechin (10), myricetin 3-O-α-L-rhamnopyranoside (11), quercetin 3-O-α-L-arabinopyranoside (12), quercetin 3-O-α-L-arabinofuranoside (13), quercetin 3-O-(3â³-galloyl)-α-L-rhamnopyranoside (14), quercetin 3-O-(2â³-galloyl)-α-L-rhamnopyranoside (15), and epicatechin 3-O-gallate (16), were isolated from the leaves of Ruprechtia polystachya Griseb. (Polygonaceae). Their structures were established on the basis of extensive 1D- and 2D-NMR experiments as well as MS analyses. All compounds, except 1, showed inhibition of the enzyme glucose-6-phosphatase in intact microsomes.
Asunto(s)
Inhibidores Enzimáticos/aislamiento & purificación , Flavonoides/aislamiento & purificación , Glucosa-6-Fosfatasa/antagonistas & inhibidores , Fenoles/aislamiento & purificación , Polygonaceae/química , Animales , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Flavonoides/farmacología , Técnicas In Vitro , Espectroscopía de Resonancia Magnética , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/enzimología , Estructura Molecular , Fenoles/farmacología , Hojas de la Planta/química , RatasRESUMEN
Galactites is a genus of flowering plants belonging to Asteraceae family. This genus is mainly represented by the Galactites elegans (All.) Nyman ex Soldano, the milky thistle, a plant of Mediterranean origin. Galactites elegans is consumed as a monofloral boar thistle honey. Chromatography separation of CHCl3 and n-BuOH extracts of aerial parts of G. elegans led to isolation of 18 pure compounds. Their structures were elucidated by 1D-and 2D-NMR spectroscopy and confirmed by mass spectrometry analysis. Sinapic aldehyde, abietin, chlorogenic acid, neochlorogenic acid, 8α-hydroxypinoresinol, 9α-hydroxypinoresinol, pinoresinol, 4-ketopinoresinol, nortrachelogenin, and erythro-guaiacylglycerol-ß-O-4'-dihydroconiferyl alcohol were isolated from CHCl3 extract, while luteolin 4'-O-glucuronide, naringenin-7-O-neohesperidoside, kaempferol-3-O-α-L-rhamnopyranosyl-(1â6)-ß-D-glucopyranoside, apigenin-7-O-α-L-rhamnopyranosyl-(1â6)-ß-D-glucopyranoside, quercitrin, quercetin-3-O-α-L-rhamnopyranosyl-(1â6)-ß-D-glucopyranoside, ciwujiatone, and nortrachelogenin-4,4'-di-O-ß-D-glucopyranoside were obtained from n-BuOH extract. The majority of isolated compounds displayed a significant antioxidant potential in vitro test (DPPH). The ability of compounds to reduce the level of peroxides in control and BHP-treated Jurkat cells was studied. The lignan derivatives were also able to reduce at 50 µM the basal level of peroxides in Jurkat cells as well as counteract peroxide increase induced by BHP treatment. Particularly 8α-hydroxypinoresinol was the most active showing 70% of peroxide level inhibition.
RESUMEN
The surface extract of an accession of Psiadia punctulata (DC.) Vatke (Asteraceae) growing in Saudi Arabia was investigated for its phytochemical composition. A bio-guided investigation of the extract led to the isolation of thirteen ent-kaurane and trachylobane diterpenes and seventeen compounds previously described, including nine flavonoids and eight diterpenes. Three flavonoids and one ent-kaurane diterpene showed antimicrobial activity with MIC100 values ranging from 25 to 150⯵g/ml. The extract showed antibacterial activity against Staphylococcus aureus (MIC100â¯=â¯180⯵g/ml) and antifungal activity against Candida albicans (MIC0â¯=â¯130⯵g/ml). The isolated 3',4',5,7-tetramethoxyflavone, at a concentration of 40⯵g/ml, displayed the ability to reduce biofilm formation of S. aureus and C. albicans by 50% and 90% respectively.
Asunto(s)
Antibacterianos/farmacología , Antifúngicos/farmacología , Diterpenos de Tipo Kaurano/farmacología , Flavonoides/farmacología , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Extractos Vegetales/química , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Antifúngicos/química , Antifúngicos/aislamiento & purificación , Asteraceae/química , Candida albicans/efectos de los fármacos , Diterpenos de Tipo Kaurano/química , Diterpenos de Tipo Kaurano/aislamiento & purificación , Flavonoides/química , Flavonoides/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Fitoquímicos/química , Extractos Vegetales/farmacología , Hojas de la Planta/química , Arabia Saudita , Staphylococcus aureus/efectos de los fármacos , Propiedades de SuperficieRESUMEN
Ononis angustissima aerial parts extract and exudate were subjected to phytochemical and biological studies. Two new natural flavonoids, (3S)-7-hydroxy-4'-methoxy-isoflavanone 3'-ß-d-glucopyranoside (1) and kaempferol 3-O-ß-d-glucopyranoside-7-O-(2'''-acetyl)-ß-d-galactopyranoside (4), and sixteen known compounds were isolated through a bio-oriented approach. Their structural characterisation was achieved using spectroscopic analyses including 2D NMR. The phytochemical profile of the extracts was also performed, and the antioxidant activity of all compounds was tested by three different assays. To get a trend in the results and to compare the antioxidant capacity among the different methods used, the obtained data were transformed to a relative antioxidant capacity index.
Asunto(s)
Antioxidantes/farmacología , Flavonoides/aislamiento & purificación , Ononis/química , Extractos Vegetales/farmacología , Flavonoides/química , Fitoquímicos/análisis , Componentes Aéreos de las Plantas/químicaRESUMEN
Two new sesquiterpenes, 8α-(4-hydroxymethacryloyl)-14-acetoxy-salonitenolide (1) and 8α-(2-hydroxymethyl 2-butenoyl)-14-acetoxy-salonitenolide (2), together with five known sesquiterpenes were isolated from the leaves of Vernonia nigritiana Oliv. & Hiern. Their structural characterization was obtained on the basis of extensive NMR spectroscopic and mass spectrometric studies.
Asunto(s)
Sesquiterpenos/aislamiento & purificación , Vernonia/química , Lactonas/aislamiento & purificación , Estructura Molecular , Sesquiterpenos/químicaRESUMEN
One new tirucallane-type triterpene {3ß, 24-dihydroxytirucallan-7,25-diene, 24-sulfate (1)}, one new sesquiterpene {7-epi-10-hydroxychabrol-1(2)-en-4,5-dione A (2)}, together with three known tirucallanes, and four aromadendranes were isolated from the leaves of Trichilia maynasiana C. DC.. Their structures were determined by means of NMR spectroscopy, mass spectrometric analysis, and chemical methods.
Asunto(s)
Meliaceae/química , Sesquiterpenos/aislamiento & purificación , Triterpenos/aislamiento & purificación , Estructura Molecular , Sesquiterpenos/química , Sesquiterpenos de Guayano , Triterpenos/químicaRESUMEN
Eleven sesquiterpene lactones, including three new natural products (1-3), were isolated from the n-butanolic extract of Ambrosia cumanensis Kunth. aerial parts. The structure of all isolated compounds was elucidated by 1D- and 2D-NMR, and MS analyses. All compounds were tested for their antiproliferative activity on HeLa, Jurkat, and U937 cell lines. Compound 3, 2,3-dehydropsilostachyn C, showed cytotoxic activity with different potency in all cell lines. By means of flow cytometric studies, compound 3 was demonstrated to induce in Jurkat cells a G2/M cell cycle block, while in U937 elicited both cytostatic and cytotoxic responses.
Asunto(s)
Ambrosia/química , Antineoplásicos Fitogénicos/química , Lactonas/química , Sesquiterpenos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Células HeLa , Humanos , Células Jurkat , Lactonas/aislamiento & purificación , Estructura Molecular , Componentes Aéreos de las Plantas/química , Extractos Vegetales/química , Sesquiterpenos/aislamiento & purificación , Células U937RESUMEN
Phenolic composition and biological activities of fruit extracts from Italian and Algerian Olea europaea L. cultivars were studied. Total phenolic and tannin contents were quantified in the extracts. Moreover 14 different phenolic compounds were identified, and their profiles showed remarkable quantitative differences among analysed extracts. Moreover antioxidant and enzymatic inhibition activities were studied. Three complementary assays were used to measure their antioxidant activities and consequently Relative Antioxidant Capacity Index (RACI) was used to compare and easily describe obtained results. Results showed that Chemlal, between Algerian cultivars, and Coratina, among Italian ones, had the highest RACI values. On the other hand all extracts and the most abundant phenolics were tested for their efficiency to inhibit α-amylase and α-glucosidase enzymes. Leccino, among all analysed cultivars, and luteolin, among identified phenolic compounds, were found to be the best inhibitors of α-amylase and α-glucosidase enzymes. Results demonstrated that Olea europaea fruit extracts can represent an important natural source with high antioxidant potential and significant α-amylase and α-glucosidase inhibitory effects.
RESUMEN
A new phenolic compound, 6'-O-sulfonyl-salidroside (1), together with fifteen known compounds, were isolated from the all parts of Limonium pruinosum. Their structures were elucidated by 1D and 2D NMR experiments including 1D TOCSY, DQF-COSY, HSQC and HMBC spectroscopy, as well as ESIMS analysis. The antioxidant activity of the extracts and all isolated compounds was evaluated by DPPH test.
Asunto(s)
Fenoles/química , Plumbaginaceae/química , Estructura MolecularRESUMEN
Entada africana roots are used in African traditional medicine for various diseases including inflammation. This application may be mediated through anti-angiogenic effects. Thus, in this study the anti-angiogenic activity of E. africana root extracts (n-hexane, chloroform, chloroform/methanol and methanol) was preliminarily evaluated by the quantitative determination of endogenous alkaline phosphatase in zebrafish embryos. A bioactivity-guided fractionation of chloroform/methanol extract yielded apigenin and robinetin as the main constituents from the most active fractions. In addition, a marked reduction on capillary formation was evidenced in chick chorioallantoic membrane after treatment with the active fractions or isolated compounds. Results obtained in this study suggest that the anti-angiogenic effects of E. africana root may account for its use in inflammatory diseases and other related pathological conditions.
Asunto(s)
Inhibidores de la Angiogénesis/química , Fabaceae/química , Extractos Vegetales/química , Raíces de Plantas/química , Inhibidores de la Angiogénesis/aislamiento & purificación , Animales , Apigenina/química , Apigenina/aislamiento & purificación , Embrión de Pollo , Embrión no Mamífero/efectos de los fármacos , Flavonoides/química , Flavonoides/aislamiento & purificación , Medicinas Tradicionales Africanas , Pez CebraRESUMEN
Angiogenesis is involved in many physiological and pathological conditions. Natural compounds with antioxidant activity have also been reported to possess potent antiangiogenic properties by regulating angiogenesis modulators such as vascular endothelial growth factor (VEGF). Based on this, we screened the antioxidant and antiangiogenic activities of Astronium graveolens leaf extracts by a DPPH test and a competitive enzyme-linked immunosorbent assay, respectively. MeOH extract expressed a significant free radical-scavenging activity (EC50 = 37.65 µg/mL) and it was able to inhibit the interaction between placental growth factor (PlGF) (placental growth factor), a VEGF family member, and its receptor Flt-1 by more than 50% at 1 mg/mL. 1,2,3,4,6-Penta-O-galloyl-d-glucopyranose, 6 is the most active compound of the extract. It exhibited a high potency in scavenging DPPH (EC50 = 2.16 µg/mL) and reduced by 58% the PlGF/Flt-1 interaction at a concentration of 50 µM. Moreover, the known compounds (1-6) have been isolated for the first time in A. graveolens.
Asunto(s)
Anacardiaceae/química , Inhibidores de la Angiogénesis/aislamiento & purificación , Inhibidores de la Angiogénesis/farmacología , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Taninos Hidrolizables/aislamiento & purificación , Taninos Hidrolizables/farmacología , Inhibidores de la Angiogénesis/química , Antioxidantes/química , Ensayo de Inmunoadsorción Enzimática , Taninos Hidrolizables/química , Factor de Crecimiento Placentario , Extractos Vegetales/química , Hojas de la Planta/química , Proteínas Gestacionales/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/efectos de los fármacos , Receptor 1 de Factores de Crecimiento Endotelial VascularRESUMEN
Phytochemical investigation of the extracts of the leaves of Siparuna thecaphora (Poepp. et Endl.) A. DC. (Siparunaceae) allowed the isolation of one monoterpene glycoside, named trans-thujane-1α,7-diol 1-O-ß-D-glucopyranoside (1) along with rutin, quercetin 3-O-ß-D-glucopyranoside and 3,4-dihydroxybenzaldehyde. Their structural characterisation was obtained on the basis of extensive spectroscopic analyses, including 1D and 2D NMR experiments and HR-ESI-MS.
Asunto(s)
Glucósidos/aislamiento & purificación , Monimiaceae/química , Monoterpenos/aislamiento & purificación , Monoterpenos Bicíclicos , Ecuador , Glucósidos/química , Monoterpenos/química , Resonancia Magnética Nuclear Biomolecular , Hojas de la Planta/química , Quercetina/análogos & derivados , Quercetina/química , Quercetina/aislamiento & purificación , EstereoisomerismoRESUMEN
Three polyprenyl-1',4'-hydroquinone derivatives, heptaprenyl-1',4'-hydroquinone (1), octaprenyl-1',4'-hydroquinone (2), and hydroxyoctaprenyl-1',4'- hydroquinone (3) were isolated from the marine sponge Sarcotragus spinosulus collected at Baia di Porto Conte, Alghero (Italy). Our findings indicate that the compounds isolated from S. spinosulus can significantly modulate the release of glutamate and acetylcholine in the rat hippocampus and cortex and might, therefore, represent the prototype of a new class of drugs regulating glutamatergic and cholinergic transmission in the mammalian central nervous system.
Asunto(s)
Acetilcolina/metabolismo , Sistema Nervioso Central/efectos de los fármacos , Sistema Nervioso Central/metabolismo , Ácido Glutámico/metabolismo , Hidroquinonas/química , Hidroquinonas/farmacología , Poríferos/química , Animales , Masculino , RatasRESUMEN
Four pregnanes: 1-methoxy-pregnan-17(R)-1,4-dien-3,16-dione (1), 1-methoxy-pregnan-17(S)-1,4-dien-3,16-dione (2), 2,3-seco-pregnan-17(S)-2,3-dioic acid-16-oxo-dimethyl ester (4), 2α,3α,16α-trihydroxy-5α-pregnan-17(R)-20-yl acetate (7), three androstanes: 1-methoxy-androstan-1,4-dien-3,16-dione (3), 2,3-seco-androstan-2,3-dioic acid-16-oxo-dimethyl ester (5), 3-methoxycarbonyl-2,3-seco-androstan-3-oic acid-16-oxo-2,19-lactone (6), together with three known pregnane derivatives, were isolated from the roots of Trichilia emetica ssp. suberosa. Their structures were determined by means of 1D and 2D NMR spectroscopy, mass spectrometry analysis, as well as by quantum chemical calculations.
Asunto(s)
Androstanos/aislamiento & purificación , Meliaceae/química , Pregnanos/aislamiento & purificación , Androstanos/química , Malí , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Corteza de la Planta/química , Raíces de Plantas/química , Pregnanos/químicaRESUMEN
ABSTRACT One new glucosidic iridoid, 6-O-veratroylbarlerin, was isolated from the chloroform/methanol extract of Isodon rubescens (Hemsl.) H.Hara, Lamiaceae aerial parts, along with the known compounds apigenin and caffeic acid. The structure of the new compound was elucidated on the basis of 1D and 2D NMR experiments and ESI-MS technique.
RESUMEN
Plants are well known for producing a wide diversity of natural compounds and several strategies have been proposed to enhance their production. Among them, somatic chromosome doubling may represent an effective and inexpensive method. The objective of the current study was to investigate the effect of polyploidization on the leaf metabolic profile and content of tetraploids produced from a wild diploid (2n=2x=24) potato species, Solanum bulbocastanum Dun. Photochemical efficiency of tetraploids was also analyzed. Results from HPLC-DAD and LC/MS analyses provided evidence that tetraploid genotypes displayed either a similar or a lower phenylpropanoids, tryptophan, tyrosine and a-chaconine content compared with the diploid parent. Similarly, no significant differences were found among genotypes both for measures of gas and for chlorophyll fluorescence, except for non-photochemical quenching (NPQ). Steroidal saponins content revealed superiority of some tetraploids with respect to the diploid parent, suggesting perturbations in the mechanism regulating the biosynthesis of such compounds following polyploidization. Lack of superiority may be attributed to the time required for adjustment, adaptation and evolution after the genomic shock induced by polyploidization, as well as the fact that an optimum ploidy level for each species may be crucial. Our results suggest that polyploidization as a strategy to enhance metabolite production cannot be generalized.