RESUMEN
Two new ent-labdane diterpenoids, hypoestesins A-B (1-2) and five new labdane diterpenoids, hypopurolides H-L (3-7), were isolated from the aerial parts of Hypoestes purpurea. All of the structures were fully determined based on extensive analysis of 1H, 13C, 2D NMR, and HRESIMS data. The absolute configurations of 1-3 was established through comparing the experimental and calculated ECD curves and the structure of 5 was confirmed by single crystal X-ray diffraction experiment. Compounds 5-7 were unusual C23 labdane diterpenoids having a γ-acetonyl-α, ß-unsaturated γ-lactone unit and each assigned as C-15 epimeric mixture. Furthermore, cytotoxic and anti-inflammatory activities of 3-7 were evaluated. The results showed that 3 had remarkable cytotoxic activity against HL-60, A549, SMMC-7721, MDA-MB-231, and SW480 cancer cell lines with IC50 values ranging from 2.35 to 17.06 µM. Compound 4 showed moderate cytotoxic activity against HL-60 and SMMC-7721 cancer cell lines with IC50 values of 15.12 ± 0.53 and 12.92 ± 0.60 µM, respectively. Furthermore, compound 4 was also found to exhibit inhibitory activity against NO production in RAW 264.7 macrophages with IC50 values of 23.56 ± 0.99 µM, compared to the positive control L-NMMA with an IC50 value of 41.11 ± 1.34 µM.
Asunto(s)
Antiinflamatorios , Antineoplásicos Fitogénicos , Diterpenos , Fitoquímicos , Componentes Aéreos de las Plantas , Componentes Aéreos de las Plantas/química , Humanos , Estructura Molecular , Antiinflamatorios/farmacología , Antiinflamatorios/aislamiento & purificación , Ratones , Animales , Línea Celular Tumoral , Células RAW 264.7 , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Diterpenos/farmacología , Diterpenos/aislamiento & purificación , Diterpenos/química , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación , Óxido Nítrico/metabolismo , ChinaRESUMEN
Eight previously undescribed diterpenoids, caesamins A-H (1-8), were separated and identified from the seeds of Caesalpinia minax Hance. Their structures were characterized by extensive spectroscopic data and X-ray crystallographic analysis. Structurally, caesamin A (1) is the first cassane-type diterpenoid with a C23 carbon skeleton containing an unusual isopropyl. Caesamin F (6) represents the first example of cleistanthane diterpenoid from the genus Caesalpinia. Caesamins B (2) and F (6) exhibited inhibitory activity against LPS-induced nitric oxide production in RAW 264.7 macrophages with IC50 values of 45.67 ± 0.92 and 42.99 ± 0.24 µM, comparable to positive control 43.69 ± 2.62 µM of NG-Monomethyl-L-arginine. Furthermore, the chemotaxonomic significance of the isolates was discussed.
Asunto(s)
Caesalpinia , Diterpenos , Óxido Nítrico , Semillas , Caesalpinia/química , Diterpenos/química , Diterpenos/farmacología , Diterpenos/aislamiento & purificación , Ratones , Semillas/química , Animales , Células RAW 264.7 , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Estructura Molecular , Lipopolisacáridos/farmacología , Lipopolisacáridos/antagonistas & inhibidores , Macrófagos/efectos de los fármacos , Relación Estructura-Actividad , Relación Dosis-Respuesta a DrogaRESUMEN
Three undescribed cassane diterpenoids, caesalpanins D-F (1-3), and seven known ones were isolated from the seeds of Caesalpinia sappan. Structures and absolute configurations of 1-3 were elucidated based on the extensive spectroscopic analysis, single-crystal X-ray diffraction analysis, and ECD calculations. Structurally, compound 1 was the first example of 18-norcassane diterpenoid and 2 was a rare 20-norcassane diterpenoid having an unusual five-membered oxygen bridge between C-10/C-18. The anti-proliferative activity of 1, 3, and 4-10 against PANC-1 cells (pancreatic ductal adenocarcinoma cell line) was evaluated, and phanginin H (4) was found to exhibit anti-cancer activity with IC50 value of 18.13 ± 0.63 µM. Compound 4 inhibited PANC-1 cell growth by arresting the cell cycle at G2/M phase via regulation of cyclin-dependent kinases, and the self-renewal and metastasis of PANC-1 cells by suppressing cancer cell stemness. Furthermore, compound 4 induced ROS generation and subsequently activated autophagy, which was demonstrated by the formation of autophagic vacuoles and dynamic change of autophagic flux. The induced ROS accumulation resulted in AMPK activation and subsequently regulation of mTORC1 activity and ULK phosphorylation, indicating that 4 triggered autophagy through ROS/AMPK/mTORC1 pathway. These findings suggested that 4 might potentially be an autophagy inducer for the therapy of pancreatic cancer.
Asunto(s)
Proteínas Quinasas Activadas por AMP , Antineoplásicos Fitogénicos , Autofagia , Caesalpinia , Proliferación Celular , Diterpenos , Ensayos de Selección de Medicamentos Antitumorales , Diana Mecanicista del Complejo 1 de la Rapamicina , Neoplasias Pancreáticas , Especies Reactivas de Oxígeno , Semillas , Caesalpinia/química , Humanos , Diterpenos/farmacología , Diterpenos/química , Diterpenos/aislamiento & purificación , Semillas/química , Autofagia/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/química , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/antagonistas & inhibidores , Proliferación Celular/efectos de los fármacos , Estructura Molecular , Línea Celular Tumoral , Relación Estructura-Actividad , Relación Dosis-Respuesta a DrogaRESUMEN
Five undescribed eudesmane sesquiterpenoids, artemilavanins A-E, and one undescribed rearranged eudesmane sesquiterpenoid, artemilavanin F, were isolated from the 95% ethanol extract of the aerial parts of Artemisia lavandulaefolia DC., along with ten known compounds. The structures and configurations of undescribed compounds were mainly elucidated by spectroscopic analyses and single-crystal X-ray diffraction analysis. Among all isolated compounds, artemilavanin F exhibited inhibitory activity on PANC-1 pancreatic cancer cells with IC50 of 9.69 ± 2.39 µM. Artemilavanin F inhibited PANC-1 cell proliferation by induction of G2/M cell cycle arrest and apoptosis mediated by downregulation of cyclin-dependent kinases and accumulation of reactive oxygen species. Moreover, artemilavanin F inhibited the colony formation, cell migration and sphere formation of PANC-1 cells, indicating the suppression of stem-cell-like phenotype of PANC-1 cells. Further results confirmed that the expression of cancer stem cell markers such as Bmi1, CD44, CD133 were inhibited by artemilavanin F. Downregulation of epithelial-mesenchymal transition (EMT) markers such as N-cadherin and Oct-4 indicated the potential of artemilavanin F in prevention of metastasis.
Asunto(s)
Artemisia , Neoplasias Pancreáticas , Sesquiterpenos de Eudesmano , Sesquiterpenos , Artemisia/química , Neoplasias Pancreáticas/tratamiento farmacológico , Sesquiterpenos de Eudesmano/farmacología , Sesquiterpenos de Eudesmano/análisis , Sesquiterpenos de Eudesmano/química , Componentes Aéreos de las Plantas/química , Sesquiterpenos/química , Estructura Molecular , Neoplasias PancreáticasRESUMEN
Three rare spirocyclohexadienone-type neolignans, magnoflorins A-C (1-3), and three known analogs (4-6), were isolated from the leaves of Magnolia liliiflora. Magnoflorin D (4) was obtained from natural resources for the first time. The chemical structures and absolute configurations of 1-4 were elucidated through detailed analysis of HR-ESI-MS, IR, 1 H, 13 C, and 2D NMR, and ECD experiments. The absolute configuration of 5 were characterized by X-ray crystallography in present study. Moreover, compounds 4 and 5 displayed moderate neuroprotective activity against corticosterone-induced PC12 cells injury at 20â µM with cell viability of 71.5±0.99 % and 73.0±1.42 %, respectively, compared to the model group with 60.83±0.93 %. Compoundâ 6 could enhance neurite outgrowth of nerve growth factor (NGF)-induced PC12 cells at 10â µM with the differentiation rate of 11.98 %, compared with 20.49 % of 50â ng/ml NGF.
Asunto(s)
Lignanos , Magnolia , Animales , Corticosterona/metabolismo , Lignanos/metabolismo , Lignanos/farmacología , Magnolia/química , Factor de Crecimiento Nervioso/metabolismo , Neuritas/metabolismo , Proyección Neuronal , Células PC12 , RatasRESUMEN
Four highly oxygenated sesquiterpenoids, illimicranolides A (1) and B (2), and illicinolides E (3) and F (4), were obtained from the fruits of Illicium micranthum Dunn, as well as one known analog, illicinolide B (5). The chemical structures of 1-4 were determined comprehensively by 1D (1 H and 13 C) and 2D (HMBC, HSQC, 1 H-1 H COSY, and ROESY) NMR, and HR-ESI-MS data. Structurally, compound 1 was an unprecedented sesquiterpenoid with a 5/5/6/5-fused tetracyclic ring system and was the first seco-prezizaane sesquiterpenoid featuring a 11,8-γ-lactone ring. Compounds 3 and 4 were the fifth and sixth examples of illicinolide-type sesquiterpenoids. Moreover, compound 1 demonstrated neurotrophic activity of NGF-induced PC12 cells with differentiation rate of 10.34 % at a concentration of 10⠵M.
Asunto(s)
Illicium , Sesquiterpenos , Animales , Frutas , Illicium/química , Lactonas/química , Estructura Molecular , Ratas , Sesquiterpenos/química , Sesquiterpenos/farmacologíaRESUMEN
Five new fawcettimine-type Lycopodium alkaloids, hupertimines A-E (1-5), were discovered from the whole plant of Huperzia serrata, along with two known alkaloids, 8α-hydroxyphlegmariurine B (6) and 8ß-hydroxyphlegmariurine B (7). The structures of 1-7 were identified through HR-MS, IR, 1 H, 13 C, and 2D NMR, and single-crystal X-ray diffraction analysis. Structurally, compound 1 was the fourth example of Lycopodium alkaloid with an ether linkage between C-5 and C-13 and 2 was the third example of Lycopodium alkaloid with a 5/5/5/5/6 pentacyclic ring system and featuring a 1-aza-7-oxabicyclo[2.2.1]heptane unit. Compounds 1-7 were tested for their BACE1 inhibitory activity. In addition, the correct 1 H- and 13 C-NMR data for 7 were reported in current study.
Asunto(s)
Alcaloides , Huperzia , Lycopodium , Alcaloides/química , Alcaloides/farmacología , Secretasas de la Proteína Precursora del Amiloide , Ácido Aspártico Endopeptidasas , Huperzia/química , Lycopodium/química , Estructura MolecularRESUMEN
Two pairs of unprecedented enantiomeric phthalide dimers, spiroligustolides A (1a/1b) and B (2a/2b), featuring a unique spiroorthoster linkage between two monomeric units to form a 5/6/5/6/6-fused ring system, were isolated from the roots of Ligusticum chuanxiong. The structures and relative configurations of 1 and 2 were determined by HR-ESI-MS, IR, and NMR spectroscopic data, coupled with single-crystal X-ray diffraction analysis, and the absolute configurations of 1a, 1b, 2a, and 2b were established by comparing the experimental and calculated electronic circular dichroism (ECD) data. Plausible biosynthetic pathway for 1 and 2 was proposed. Moreover, compounds 1, 1b, and 2b showed remarkable inhibitory activities on Cav3.1 calcium channel with IC50 values of 8.34, 7.08, and 8.60 µM, respectively.
Asunto(s)
Benzofuranos , Ligusticum , Benzofuranos/química , Benzofuranos/farmacología , Canales de Calcio , Ligusticum/química , Estructura Molecular , EstereoisomerismoRESUMEN
Persistent activation of hepatic gluconeogenesis is a main cause of fasting hyperglycemia in patients with type 2 diabetes (T2D), and the salt-induced kinase 1 (SIK1) acts as a key modulator in regulating hepatic gluconeogenesis. Recently, we first reported phanginin A (PA, 1), a natural cassane diterpenoid isolated from the seeds of Caesalpinia sappan, exhibited potent anti-diabetic effect through activation of SIK1 and increasing PDE4 activity to inhibit hepatic gluconeogenesis pathway by suppressing the cAMP/PKA/CREB pathway in the liver. In present study, we designed and prepared 25 PA derivatives and their structure-activity relationship (SAR) for gluconeogenesis inhibitory activity were established. Among them, compound 7 exhibited remarkable inhibitory activity on hepatic gluconeogenesis by enhancing the SIK1 phosphorylation and ameliorated the hyperglyceamia of type 2 diabetic mice. Our results supported that compound 7 could be served as a potential candidate for the treatment of T2D.
Asunto(s)
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Animales , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Gluconeogénesis , Hígado , Ratones , Proteínas Serina-Treonina Quinasas , Transducción de SeñalRESUMEN
Two new seco-prezizaane-type sesquiterpenes, 2ß-hydroxy-6-deoxyneoanisatin (1) and 3,4-anhydro-2-oxo-1α-hydroxy-6-deoxyneoanisatin (2), and two new prenylated C6 -C3 compounds, illilanceofunones A (3) and B (4), were obtained from the fruits of Illicium lanceolatum, along with four known prenylated C6 -C3 compounds (5-8). Their structures were proposed through HR-ESI-MS, 1 H, 13 C, and 2D NMR data interpretation. Moreover, the absolute configuration of 1 and 2 were further assigned by single-crystal X-ray diffraction analysis and electronic circular dichroism (ECD) calculations, respectively. Illihenryipyranol A (6) exhibited neuroprotective activity against MPP+ -induced PC12â cell damage in a dose-dependent manner.
Asunto(s)
Illicium/química , Fármacos Neuroprotectores/química , Sesquiterpenos/química , Animales , Supervivencia Celular/efectos de los fármacos , Dicroismo Circular , Frutas/química , Frutas/metabolismo , Illicium/metabolismo , Espectroscopía de Resonancia Magnética , Conformación Molecular , Fármacos Neuroprotectores/aislamiento & purificación , Fármacos Neuroprotectores/farmacología , Células PC12 , Extractos Vegetales/química , Prenilación , Ratas , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos/farmacología , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
Ten previously undescribed cassane diterpenoids, cassabonducins A-J, and eleven known compounds were isolated from the seeds of Caesalpinia bonduc. The structures of the undescribed compounds were elucidated by extensive analysis of spectroscopic data (IR, HRESIMS, and 1H, 13C and 2D NMR) and their absolute configurations were determined by the ECD data and single-crystal X-ray diffraction analysis. ε-Caesalpin-â ¦ was obtained from natural resources for the first time. Cassabonducin A possessed noteworthy inhibitory activity against LPS-induced nitric oxide (NO) production in RAW 264.7 macrophages with IC50 value of 6.12 µM. Cassabonducin D and neocaesalpin N showed moderate α-glucosidase inhibition at the concentration of 50 µM with inhibitory capacities of 47.17% and 43.83%, respectively.
Asunto(s)
Caesalpinia , Diterpenos , Diterpenos/farmacología , Espectroscopía de Resonancia Magnética , Estructura Molecular , Óxido Nítrico , Semillas , alfa-GlucosidasasRESUMEN
Catharanthus roseus is a well-known traditional herbal medicine for the treatment of cancer, hypertension, scald, and sore in China. Phytochemical investigation on the twigs and leaves of this species led to the isolation of two new monoterpene indole alkaloids, catharanosines A (1) and B (2), and six known analogues (3-8). Structures of 1 and 2 were established by 1H-, 13C- and 2D-NMR, and HREIMS data. The absolute configuration of 1 was confirmed by single-crystal X-ray diffraction analysis. Compound 2 represented an unprecedented aspidosperma-type alkaloid with a 2-piperidinyl moiety at C-10. Compounds 6-8 exhibited remarkable Cav3.1 low voltage-gated calcium channel (LVGCC) inhibitory activity with IC50 values of 11.83 ± 1.02, 14.3 ± 1.20, and 14.54 ± 0.99 µM, respectively.
Asunto(s)
Bloqueadores de los Canales de Calcio/farmacología , Canales de Calcio Tipo T/química , Catharanthus/química , Alcaloides Indólicos/farmacología , Monoterpenos/farmacología , Extractos Vegetales/farmacología , Bloqueadores de los Canales de Calcio/química , Canales de Calcio Tipo T/metabolismo , Relación Dosis-Respuesta a Droga , Alcaloides Indólicos/química , Conformación Molecular , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Estructura Molecular , Monoterpenos/química , Extractos Vegetales/química , Relación Estructura-ActividadRESUMEN
A new neo-clerodane diterpenoid, salvihispin H (1), and six known ones (2-7) were identified from the aerial parts of Salvia hispanica L. The structure and absolute configuration of 1 were elucidated by extensive analysis of spectroscopic (1 H, 13 C, and 2D NMR, and HR-ESI-MS) and single-crystal X-ray diffraction data. The anti-diabetic effects of salvihispin H (1) and salvifaricin (2) were evaluated in diabetic db/db mice. The data showed that 1 and 2 could significantly reduce fasting blood glucose level and improve insulin resistance, and compound 1 exerted glucose-lowering effect more quickly than metformin. In addition, 1 and 2 could also reduce serum TG level in db/db mice. These results demonstrated that compounds 1 and 2 could be considered as potent candidates for the therapy of type 2 diabetes mellitus (T2DM).
Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diterpenos de Tipo Clerodano/farmacología , Hipoglucemiantes/farmacología , Componentes Aéreos de las Plantas/química , Salvia/química , Animales , Glucemia/efectos de los fármacos , Cristalografía por Rayos X , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Modelos Animales de Enfermedad , Diterpenos de Tipo Clerodano/química , Hipoglucemiantes/química , Masculino , Ratones , Ratones Endogámicos C57BL , Modelos Moleculares , Estructura MolecularRESUMEN
Pseudolaric acid A (PAA), one of the main bioactive ingredients in traditional medicine Pseudolarix cortex, exhibits remarkable anticancer activities. Yet its mechanism of action and molecular target have not been investigated and remain unclear. In this work, mechanistic study showed that PAA induced cell cycle arrest at G2/M phase and promoted cell death through caspase-8/caspase-3 pathway, demonstrating potent antiproliferation and anticancer activities. PAA was discovered to be a new Hsp90 inhibitor and multiple biophysical experiments confirmed that PAA directly bind to Hsp90. Active PAA-probe was designed, synthesized and biological evaluated. It was subsequently employed to verify the cellular interaction with Hsp90 in HeLa cells through photoaffinity labeling approach. Furthermore, NMR experiments showed that N-terminal domain of Hsp90 and essential groups in PAA are important for the protein-inhibitor recognition. Structure-activity relationship studies revealed the correlation between its Hsp90 inhibitory activity with anticancer activity. This work proposed a potential mechanism involved with the anticancer activity of PAA and will improve the appreciation of PAA as a potential cancer therapy candidate.
Asunto(s)
Antineoplásicos/farmacología , Diterpenos/farmacología , Descubrimiento de Drogas , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Antineoplásicos/síntesis química , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Diterpenos/síntesis química , Diterpenos/química , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Proteínas HSP90 de Choque Térmico/aislamiento & purificación , Proteínas HSP90 de Choque Térmico/metabolismo , Humanos , Estructura Molecular , Relación Estructura-Actividad , Células Tumorales CultivadasRESUMEN
Two unprecedented tetranorlanostane triterpenoids, poricolides A (1) and B (2), and two new lanostane triterpenoids, 3ß-acetoxy-24-methyllanosta-8,16,24(31)-trien-21-oic acid (3) and 3ß-acetoxylanosta-7,9(11),16,23-tetraen-21-oic acid (4), were isolated from the epidermis of Poria cocos. The structures of 1-4 were determined via analysis of 1 H-, 13 C-, and 2D-NMR, and HR-ESI-MS data, and the absolute configurations of 1 and 3 were established by single-crystal X-ray diffraction analysis. Compounds 1 and 2 were the first report of tetranorlanostane triterpenoid having a δ-lactone ring at C(17). Compounds 3 and 4 were rare lanostane triterpenoids having a double bond between C(16) and C(17). Compounds 1-4 exhibited potent antiproliferative effects against A549, SMMC-7721, MCF-7, and SW480 cancer cell lines with IC50 values from 16.19±0.38 to 27.74±1.12â µM.
Asunto(s)
Antineoplásicos/farmacología , Epidermis/química , Triterpenos/farmacología , Wolfiporia/química , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cristalografía por Rayos X , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Modelos Moleculares , Conformación Molecular , Estereoisomerismo , Triterpenos/química , Triterpenos/aislamiento & purificaciónRESUMEN
One new limonoid, named 19-hydroxy methyl isoobacunoate diosphenol (1); one new degraded limonoid, named 9α-methoxyl dictamdiol (9); two new quinolone alkaloids, 1-methyl-3-[(7E,9E,12Z)-7,9,12-pentadecadienyl]-4(1H)-quinolone (11) and 1-methyl-3-[(7E,9E,11E)-7,9,11-pentadecadienyl]-4(1H)-quinolone (12), along with eight known compounds, evodol (2), 7ß-acetoxy-5-epilimonin (3), rutaevine (4), 6ß-acetoxy-5-epilimonin (5), limonin (6), obacunone (7), clauemargine L (8), hiiranlactone E (10) were isolated from the fruits of Evodia rutaecarpa (Juss.) Benth.. Structures of the four new compounds were elucidated on the basis of extensive spectroscopic techniques, including 1D and 2D NMR techniques. Compounds 3, 5, 9, 11 and 12 showed obviously cytotoxic activity against six human tumor lines, while compounds 11, 12 displayed anti-platelet aggregation induced by ADP at 50 µM and 100 µM.
Asunto(s)
Alcaloides/farmacología , Antineoplásicos Fitogénicos/farmacología , Evodia/química , Limoninas/farmacología , Quinolonas/farmacología , Alcaloides/aislamiento & purificación , Antineoplásicos Fitogénicos/aislamiento & purificación , Plaquetas/efectos de los fármacos , Línea Celular Tumoral , China , Frutas/química , Humanos , Limoninas/aislamiento & purificación , Estructura Molecular , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Agregación Plaquetaria/efectos de los fármacos , Quinolonas/aislamiento & purificaciónRESUMEN
Six new rearranged neoclerodane diterpenoids (1-6), as well as three known ones, were obtained from the aerial part of Salvia hispanica L. Their structures were elucidated by extensive analysis of spectroscopic data (1D, 2D NMR, and HRESIMS) and Mosher's method. The absolute configurations of 1, 2, and 4 were determined by single-crystal X-ray diffraction analysis. All isolated compounds were evaluated for their cardioprotective effects against H2O2-induced cardiomyocytes injury, and compound 5 showed statistically significant cardioprotective effect in vitro assays.
Asunto(s)
Cardiotónicos/farmacología , Diterpenos de Tipo Clerodano/farmacología , Miocitos Cardíacos/efectos de los fármacos , Salvia/química , Animales , Cardiotónicos/aislamiento & purificación , Células Cultivadas , Diterpenos de Tipo Clerodano/aislamiento & purificación , Peróxido de Hidrógeno , Estructura Molecular , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Componentes Aéreos de las Plantas/química , Ratas WistarRESUMEN
Huperserratines A (1) and B (2), two Lycopodium alkaloids with an unprecedented 5-aza-bicyclo[10.4.0]hexadecane skeleton and an oxime function, were isolated from Huperzia serrata. Their structures including absolute configurations were determined by extensive NMR spectroscopic and X-ray diffraction analysis. Compounds 1 and 2 were the first examples of macrocyclic Lycopodium alkaloids with an aza-12-membered ring. A plausible biogenetic pathway of these compounds was also proposed. Compound 1 exhibited moderate anti-HIV-1 activity with an EC50 of 52.91 µg/mL and a therapy index greater than 3.78.
Asunto(s)
Alcaloides , Huperzia , Lycopodium , Alcaloides/farmacología , Estructura Molecular , EsqueletoRESUMEN
Three dimeric cassane diterpenoids, caesalpanins A-C, were isolated from the seeds of Caesalpinia sappan L., as well as three known compounds. Their structures were determined via analysis of 1D-, 2D-NMR, and HR-ESI-MS data. Caesalpanins A and B were the second and third compounds that presented a nitrogen-containing cassane diterpenoid dimer linked through one ether bond between C-19 and C-20'. Caesalpanin B exhibited moderate cytotoxic activity against MCF-7â cell lines with IC50 value of 29.98â µm. Caesalpanins A and B had weak inhibitory effects against LPS-induced nitric oxide (NO) production in RAW 264.7 macrophages at 50â µm with inhibitory rate of 36.01 % and 32.93 %, respectively.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Caesalpinia/química , Diterpenos/farmacología , Semillas/química , Animales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Proliferación Celular/efectos de los fármacos , Diterpenos/química , Diterpenos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Células MCF-7 , Ratones , Conformación Molecular , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Células RAW 264.7 , Relación Estructura-ActividadRESUMEN
Phytochemical investigation on the pericarps of Illicium difengpi lead to the isolation and structure elucidation of a new sesquiterpene, sesquicaranoic acid C (1), a new neolignan, difengpiol C (2), and 10 known compounds. The structures and absolute configurations of two new compounds were determined by a combination of NMR and CD spectroscopic analyses. All isolates were evaluated for their inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells.