RESUMEN
The formation of adventitious roots (ARs) derived from hypocotyl is the most important morphological adaptation to waterlogging stress in Cucumis sativus (cucumber). Our previous study showed that cucumbers with the gene CsARN6.1, encoding an AAA ATPase domain-containing protein, were more tolerant to waterlogging through increased AR formation. However, the apparent function of CsARN6.1 remained unknown. Here, we showed that the CsARN6.1 signal was predominantly observed throughout the cambium of hypocotyls, where de novo AR primordia are formed upon waterlogging treatment. The silencing of CsARN6.1 expression by virus-induced gene silencing and CRISPR/Cas9 technologies adversely affects the formation of ARs under conditions of waterlogging. Waterlogging treatment significantly induced ethylene production, thus upregulating CsEIL3 expression, which encodes a putative transcription factor involved in ethylene signaling. Furthermore, yeast one-hybrid, electrophoretic mobility assay and transient expression analyses showed that CsEIL3 binds directly to the CsARN6.1 promoter to initiate its expression. CsARN6.1 was found to interact with CsPrx5, a waterlogging-responsive class-III peroxidase that enhanced H2 O2 production and increased AR formation. These data provide insights into understanding the molecular mechanisms of AAA ATPase domain-containing protein and uncover a molecular mechanism that links ethylene signaling with the formation of ARs triggered by waterlogging.
Asunto(s)
Cucumis sativus , Cucumis sativus/genética , Cucumis sativus/metabolismo , Etilenos/metabolismo , Hipocótilo/metabolismo , Regulación de la Expresión Génica de las Plantas , ATPasas Asociadas con Actividades Celulares Diversas/genética , Raíces de Plantas/genética , Raíces de Plantas/metabolismoRESUMEN
Twelve new alkaloids, scolopenolines A-L (1-7, 9-11, 13, 14), along with six known analogues, were isolated from Scolopendra subspinipes mutilans, identified by analysis of spectroscopic data and quantum chemical and computational methods. Scolopenoline A (1), a unique guanidyl-containing C14 quinoline alkaloid, features a 6/6/5 ring backbone. Scolopenoline B (2) is a novel sulfonyl-containing heterodimer comprising quinoline and tyramine moieties. Scolopenoline G (7) presents a rare C12 quinoline skeleton with a 6/6/5 ring system. Alkaloids 1, 8, 10, and 15-18 display anti-inflammatory activity, while 10 and 16-18 also exhibit anti-renal-fibrosis activity. Drug affinity responsive target stability and RNA-interference assays show that Lamp2 might be a potentially important target protein of 16 for anti-renal-fibrosis activity.
Asunto(s)
Alcaloides , Animales Ponzoñosos , Quilópodos , Animales , Alcaloides/farmacología , Alcaloides/química , Alcaloides/aislamiento & purificación , Estructura Molecular , Artrópodos/química , Fibrosis/tratamiento farmacológico , Riñón/efectos de los fármacos , Quinolinas/farmacología , Quinolinas/química , Antiinflamatorios/farmacología , Antiinflamatorios/química , HumanosRESUMEN
Four undescribed compounds including one aromatic glucoside derivative, cordyceglycoside A (1), one new isoleucine derivative inner salt, cordycepisosalt A (2), a rare four-membered lactam, cinerealactam B (3), and one sesquiterpene derivative, cordycepsetp A (4), together with six known compounds were isolated from Cordyceps militaris. The structures including absolute configurations of these new compounds, were unambiguously elucidated by spectroscopic data analysis and single crystal X-ray diffraction. Biological evaluation of compounds 1-4 showed that 3 displays anti-renal fibrotic activities in TGF-ß1 induced NRK-52e cells. Furthermore, DARTS coupled with LC-MS/MS analysis was used to identify candidate target proteins for 3. Subsequently, C1qbp knockdown using siRNA allowed us to validate the target protein of 3.
Asunto(s)
Cordyceps , Cordyceps/química , Cordyceps/metabolismo , Cromatografía Liquida , Espectrometría de Masas en Tándem , Análisis Espectral , FibrosisRESUMEN
Three pairs of enantiomers and one achiral molecule that are new ethylated derivatives of sulfur and nitrogen-containing compounds named mantidisamides E-H (1-4), along with twenty known ones (5-24), were derived from the ethanol extract of Tenodera sinensis Saussure. The structures of these new compounds and their absolute configurations were assigned on the basis of spectroscopic analyses and computational methods. The assessment of activities in NRK-52e cells induced by TGF-ß1 demonstrated that the previously undescribed compounds 1 and 2 exhibited a significant capacity to inhibit the expression of proteins (fibronectin, collagen I, and α-SMA). Moreover, the biological activity of these compounds was found to increase with rising concentrations. Notably, compounds 1-4 should be artifacts; however, undescribed compounds 1 and 2, which possessed obvious biological activity, might be attractive for chemists and biologists due to the potential for more detailed exploration of their properties. It is worth mentioning that compounds 1 and 2 remain novel structures even in the absence of the ethoxy group.
Asunto(s)
Nitrógeno , Animales , Ratas , Nitrógeno/química , Azufre/química , Línea Celular , Estructura Molecular , FibrosisRESUMEN
Blapspirooxindoles A-C (1-3), three novel spirooxindole alkaloids with a unique spiro[chromane-4,3'-indoline]-2,2'-dione motif, blapcumaranons A and B (4 and 5), two new 2-cumaranon derivatives, blapoxindoles A-J (6-15), ten new oxindole alkaloid derivatives, along with one known compound (16), were isolated from the whole bodies of Blaps japanensis. Their structures including absolute configurations were determined by using spectroscopic, X-ray crystallographic, and computational methods. Compounds 1-11 and 13 exist as racemic mixtures in nature, and their (-)- and (+)-antipodes were separated by chiral HPLC. Biological evaluations of these compounds were determined with multiple assays including anti-tumor, anti-inflammatory, and renal protection activities in vitro. Several compounds displayed effective activity in one or more assays.
Asunto(s)
Alcaloides , Antineoplásicos , Escarabajos , Neoplasias , Animales , Escarabajos/química , Antineoplásicos/farmacología , Antineoplásicos/química , Alcaloides/farmacología , Oxindoles/farmacología , Estructura MolecularRESUMEN
Investigation on the chemical components of Valeriana jatamansi Jones (Caprifoliaceae), a new lignan with pyran-ring, dipsalignan G (1), along with eight known compounds (2-9) were isolated. Their structures were elucidated by extensive analysis of 1D, 2D NMR and HR-ESI-MS spectroscopic data. Additionally, possible biosynthetic pathway of 1 was proposed. Finally, biological evaluation results showed that 8 had significant scavenging ability to ABTS and DPPH free radicals, with IC50 values of 1.35 ± 0.01 and 2.94 ± 0.01 µg/ml, respectively.
RESUMEN
Six new compounds, including a tetralone 1, two xanthones 2 and 3, a flavan derivative 4, and two nor-diterpenoids 7 and 8, accompanied by two known flavan derivatives 5 and 6 and a known olefine acid (9) were isolated from whole bodies of Kronopolites svenhedini (Verhoeff). The structures of the new compounds were determined by 1D and 2D nuclear magnetic resonance (NMR) and other spectroscopic methods, as well as computational methods. Selected compounds were evaluated for their biological properties against a mouse pancreatic cancer cell line and inhibitory effects on iNOS and COX-2 in RAW264.7 cells.
RESUMEN
[This corrects the article DOI: 10.3762/bjoc.19.59.].
RESUMEN
Aquilarines A (1) and B (2), two unprecedented sesquiterpenoid-chromone heterohybrids, were isolated from Aquilaria sinensis agarwood. 1 is an alkaloid featuring an unusual pyridine nucleus, and 2 possesses a rare sesquiterpenoid-chromone skeleton via a C-C bond. A plausible biosynthetic pathway for 1 and 2 was proposed. Both 1 and 2 could significantly inhibit the expression of extracellular matrix components, and α-SMA at low concentrations in TGF-ß1 induced two types of kidney cells (NRK 52E and NRK 49F) featuring selective inhibition of Smad3 instead of Smad2 phosphorylation, showing their potential in renal fibrosis.
Asunto(s)
Sesquiterpenos , Thymelaeaceae , Cromonas , Fibrosis , Humanos , Fosforilación , Sesquiterpenos/farmacología , Proteína smad3 , Thymelaeaceae/químicaRESUMEN
Sinkianlignans A - D (1-4), four new sesquilignans with an unusual architectures was characterized with a rarely α-γ', ß-γ', and γ-γ' linkage pattern, and sinkianlignans E - F (5 and 6), two lignans, were isolated from the Ferula sinkiangensis. Hypothetic biosynthetic pathway of compound 3 contain a newly formed six-membered C-ring by Diels-Alder cycloaddition. The structures of isolates were established by spectroscopic techniques and computational methods. Biological evaluation of all the isolated compounds revealed that compounds 2a and 2b could inhibit IL-6 and TNF-α production in lipopolysaccharide (LPS) induced RAW264.7 cells in a dose-dependent manner.
Asunto(s)
Ferula , Sesquiterpenos , Antiinflamatorios/farmacología , Ferula/química , Estructura Molecular , Resinas de Plantas , Sesquiterpenos/químicaRESUMEN
Cardiac hypertrophy is a common adaptive response to a variety of stimuli, but prolonged hypertrophy leads to heart failure. Hence, discovery of agents treating cardiac hypertrophy is urgently needed. In the present study, we investigated the effects of QF84139, a newly synthesized pyrazine derivative, on cardiac hypertrophy and the underlying mechanisms. In neonatal rat cardiomyocytes (NRCMs), pretreatment with QF84139 (1-10 µM) concentration-dependently inhibited phenylephrine-induced hypertrophic responses characterized by fetal genes reactivation, increased ANP protein level and enlarged cardiomyocytes. In adult male mice, administration of QF84139 (5-90 mg·kg-1·d-1, i.p., for 2 weeks) dose-dependently reversed transverse aortic constriction (TAC)-induced cardiac hypertrophy displayed by cardiomyocyte size, left ventricular mass, heart weights, and reactivation of fetal genes. We further revealed that QF84139 selectively activated the AMPK signaling pathway without affecting the phosphorylation of CaMKIIδ, ERK1/2, AKT, PKCε, and P38 kinases in phenylephrine-treated NRCMs and in the hearts of TAC-treated mice. In NRCMs, QF84139 did not show additive effects with metformin on the AMPK activation, whereas the anti-hypertrophic effect of QF84139 was abolished by an AMPK inhibitor Compound C or knockdown of AMPKα2. In AMPKα2-deficient mice, the anti-hypertrophic effect of QF84139 was also vanished. These results demonstrate that QF84139 attenuates the PE- and TAC-induced cardiac hypertrophy via activating the AMPK signaling. This structurally novel compound would be a promising lead compound for developing effective agents for the treatment of cardiac hypertrophy.
Asunto(s)
Proteínas Quinasas Activadas por AMP/efectos de los fármacos , Cardiomegalia/patología , Miocitos Cardíacos/efectos de los fármacos , Animales , Animales Recién Nacidos , Aorta/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Masculino , Ratones , Ratones Endogámicos C57BL , Tamaño de los Órganos/efectos de los fármacos , Fenilefrina/farmacología , ARN Interferente Pequeño/farmacología , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacosRESUMEN
Belamcandaoids A-N (1-14), fourteen new triterpenoids were isolated from the seeds of Belamcanda chinensis. Their structures including absolute configurations were assigned by using spectroscopic, computational, and crystallographic methods. All the compounds except 1 and 2 are 3,4-seco-triterpenoids belonging to fernane type. Biological evaluation results indicated that 3 and 13 could reduce fibronectin and collagen I expression respectively in TGF-ß1 induced kidney proximal tubular cells.
Asunto(s)
Células Epiteliales/efectos de los fármacos , Matriz Extracelular/efectos de los fármacos , Iridaceae/química , Extractos Vegetales/farmacología , Factor de Crecimiento Transformador beta1/antagonistas & inhibidores , Triterpenos/farmacología , Animales , Línea Celular , Teoría Funcional de la Densidad , Relación Dosis-Respuesta a Droga , Células Epiteliales/metabolismo , Matriz Extracelular/metabolismo , Túbulos Renales Proximales/efectos de los fármacos , Túbulos Renales Proximales/metabolismo , Estructura Molecular , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Ratas , Semillas/química , Relación Estructura-Actividad , Factor de Crecimiento Transformador beta1/metabolismo , Triterpenos/química , Triterpenos/aislamiento & purificaciónRESUMEN
Seven new meroterpenoids, lucidumones B-H (1 and 3-8), along with one known meroterpenoid (2), were isolated from the fruiting bodies of Ganoderma lucidum. The structures of the new compounds were assigned by spectroscopic and computational methods. All the isolated compounds were tested for their inhibition on human cancer cell migration. It was found that compounds (-)-1, (+)-2, (-)-4, (+)-6, and (+)-8 could significantly inhibit cell migration in KYSE30 cell line. Further examination disclosed that cell migration inhibition of (+)-6 and (+)-8 might be related with downregulation of N-cadherin.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Ganoderma/química , Inhibidores de Proteínas Quinasas/farmacología , Terpenos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/metabolismo , Humanos , Simulación del Acoplamiento Molecular , Estructura Molecular , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/aislamiento & purificación , Relación Estructura-Actividad , Terpenos/química , Terpenos/aislamiento & purificaciónRESUMEN
Chuanxiongdiolides R4-R6 (1-3), three novel phthalide dimers featuring two classes of unreported monomeric units (ligustilide/senkyunolide A and ligustilide/neocnidilide) with an unprecedented linkage style (3a,7'/7a,7'a), were isolated from the aerial parts of Ligusticum chuanxiong, together with three pairs of enantiomeric phthalide dimers [(-)/(+)-4a/4b, 5a/5b, and 6a/6b]. The bioassays revealed that compounds 1, 3, 4, 5, and 6 showed significant vasodilation effects, and the mechanism may be attributed to Cav1.2 activation blockade. Based on the established compounds library, the structure activity relationship of the phthalides was proposed. Our findings afford possible leads for developing new vasodilator against cardiovascular and cerebrovascular diseases such as hypertension and ischemic stroke.
Asunto(s)
Benzofuranos/farmacología , Compuestos Heterocíclicos de Anillo en Puente/farmacología , Ligusticum/química , Vasodilatadores/farmacología , Animales , Benzofuranos/química , Benzofuranos/aislamiento & purificación , Benzofuranos/metabolismo , Bloqueadores de los Canales de Calcio/química , Bloqueadores de los Canales de Calcio/aislamiento & purificación , Bloqueadores de los Canales de Calcio/metabolismo , Bloqueadores de los Canales de Calcio/farmacología , Canales de Calcio Tipo L/metabolismo , Células HEK293 , Compuestos Heterocíclicos de Anillo en Puente/síntesis química , Compuestos Heterocíclicos de Anillo en Puente/aislamiento & purificación , Compuestos Heterocíclicos de Anillo en Puente/metabolismo , Humanos , Simulación del Acoplamiento Molecular , Estructura Molecular , Componentes Aéreos de las Plantas/química , Unión Proteica , Conejos , Ratas Sprague-Dawley , Estereoisomerismo , Relación Estructura-Actividad , Vasodilatadores/química , Vasodilatadores/aislamiento & purificación , Vasodilatadores/metabolismoRESUMEN
Meyeniines A-C (1-3), three new lignans, two known neolignans (4-5), and three known lignans (6-8) were isolated from the rhizomes of Lepidium meyenii. Their structures were identified by comprehensive spectroscopic analyses and computational methods. Compound 1 represents a unique lignan featuring an aromatic ring migration. Compoundsâ 2 and 4-6 were analyzed by chiral HPLC column as enantiomers. Biological evaluation revealed that compoundâ 8 could inhibit IL-6 production in lipopolysaccharide (LPS) induced RAW264.7 cells in a dose-dependent manner.
Asunto(s)
Antiinflamatorios/química , Lepidium/metabolismo , Lignanos/química , Animales , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Supervivencia Celular/efectos de los fármacos , Interleucina-6/metabolismo , Lignanos/aislamiento & purificación , Lignanos/farmacología , Lipopolisacáridos/farmacología , Macrófagos/citología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Espectroscopía de Resonancia Magnética , Ratones , Conformación Molecular , Extractos Vegetales/química , Células RAW 264.7RESUMEN
Commiphorane K (1), a new dinorditerpenoid, commiphoranes L-N (2-4), three new germacrane-type sesquiterpenoids, and commiphorane O (5), one new guaiane-type sesquiterpenoid, were isolated from Resina Commiphora. Their structures were characterized by spectroscopic and computational methods. In particular, the structure of 4 was confirmed by X-ray crystallography. Compounds 2-5 were evaluated for their anti-inflammatory activities. The result shows that compound 2 suppresses lipopolysaccharide (LPS)-stimulated production of TNF-α in RAW264.7 cells in a dose-dependent manner.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Commiphora/química , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Animales , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/aislamiento & purificación , Supervivencia Celular/efectos de los fármacos , Cristalografía por Rayos X , Relación Dosis-Respuesta a Droga , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Ratones , Modelos Moleculares , Estructura Molecular , Células RAW 264.7 , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
Five new compounds including three pairs of enantiomeric xanthine analogues, parvaxanthines D-F (1-3), two new guanosine derivatives, asponguanosines C and D (6 and 7), along with two known adenine derivatives were isolated from the insect Cyclopelta parva. Racemic 1-3 were further separated by chiral HPLC. Their absolute configurations were assigned by spectroscopic and computational methods. It is interesting that all of these isolates are natural product hybrids. Antiviral, immunosuppressive, antitumor and anti-inflammatory properties of all the isolates were evaluated.
Asunto(s)
Antiinflamatorios/farmacología , Antineoplásicos/farmacología , Antivirales/farmacología , Productos Biológicos/farmacología , Guanosina/química , Insectos/química , Xantinas/química , Animales , Productos Biológicos/química , Células Cultivadas , Chlorocebus aethiops , Cromatografía Líquida de Alta Presión/métodos , Ratones , Ratones Endogámicos C57BL , Estructura Molecular , EstereoisomerismoRESUMEN
Five new nitrogen-containing compounds (1-3, 5, and 6), two compounds which was firstly isolated from natural origin (7 and 10), along with six known ones, were isolated from the ethanol extract of the whole bodies of Polyphaga plancyi. The structures of the new compounds including their absolute configurations at stereogenic centers were assigned on the basis of spectroscopic analyses and computational methods. Racemic 10 was separated by chiral HPLC. Biological activities of these isolates against extracellular matrix components in rat renal proximal tubular cells, EV71, COX-2, ROCK2, JAK3, and tuberculosis were evaluated. Importantly, 8 was found to be a selective Smad3 phosphorylation inhibitor.
Asunto(s)
Antituberculosos/farmacología , Productos Biológicos/farmacología , Escarabajos/química , Ciclooxigenasa 2/metabolismo , Inhibidores Enzimáticos/farmacología , Janus Quinasa 3/antagonistas & inhibidores , Tuberculosis/tratamiento farmacológico , Animales , Antituberculosos/química , Antituberculosos/aislamiento & purificación , Productos Biológicos/química , Productos Biológicos/aislamiento & purificación , Células Cultivadas , Teoría Funcional de la Densidad , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/aislamiento & purificación , Janus Quinasa 3/metabolismo , Estructura Molecular , Ratas , Relación Estructura-ActividadRESUMEN
Two structurally novel meroterpenoids, ganodermaones A (1) and B (2), were isolated from Ganoderma fungi (G. cochlear and G. lucidum). The structures of 1 and 2 were assigned by spectroscopic, computational, and X-ray diffraction methods. Compounds 1 and 2 represent the first examples of meroterpenoids in Ganoderma fungal species featuring with carbon migration. The plausible biosynthetic pathway for 1 was proposed. Biological evaluation showed that both 1 and 2 could inhibit renal fibrosis in TGF-ß1-induced kidney proximal tubular cells.
Asunto(s)
Ganoderma/química , Terpenos/química , Animales , Carbono/química , Carbono/metabolismo , Línea Celular , Supervivencia Celular/efectos de los fármacos , Colágeno Tipo I/metabolismo , Fibronectinas/metabolismo , Ganoderma/metabolismo , Túbulos Renales Proximales/citología , Túbulos Renales Proximales/efectos de los fármacos , Túbulos Renales Proximales/metabolismo , Espectroscopía de Resonancia Magnética , Conformación Molecular , Ratas , Terpenos/aislamiento & purificación , Terpenos/farmacología , Factor de Crecimiento Transformador beta1/farmacologíaRESUMEN
Pipajiains H-J (1-3), three new phenolic derivatives with an unusual sulfone group, pipajiamides A-C (4-6), three new amide derivatives, pipajiaine A (7), one new imidazole analogue, and pipajiaine B (8), a pair of new pyrrolidine derivatives, along with three known compounds were isolated from the insect Blaps japanensis. Their structures were identified by spectroscopic and computational methods. Chiral HPLC was used to separate the (-)- and (+)-antipodes of 4 and 8. Biological activities of all the new compounds against extracellular matrix in rat renal proximal tubular cells, human cancer cells (A549, Huh-7, and K562), COX-2, ROCK1, and JAK3 were evaluated. The results show that compounds 2, (+)-4, and (-)-4 are active against kidney fibrosis, whereas, compound 9 is active toward human cancer cells, inflammation, and JAK3 kinase.