RESUMEN
Nigegladines A-C (1-3), three thymoquinone dimers, were isolated from the seeds of Nigella glandulifera. Racemic 1 possesses a unique tricyclo[5.4.0.12,6]dodecane carbon skeleton, and compounds 2 and 3 are two unusual diterpenoid alkaloids with indole cores. Their structures were determined by extensive spectroscopic analyses, and that of 1 was confirmed by single-crystal X-ray diffraction. Both (+)-1 and (-)-1 exhibited significant protective effects against hypoxia/reoxygenation-induced H9c2 myocardial cell injury.
Asunto(s)
Alcaloides/química , Benzoquinonas/química , Nigella/química , Extractos Vegetales/química , Alcaloides/aislamiento & purificación , Animales , Benzoquinonas/aislamiento & purificación , Benzoquinonas/farmacología , Vías Biosintéticas , Hipoxia de la Célula/efectos de los fármacos , Línea Celular , Dimerización , Humanos , Miocardio/citología , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Ratas , Semillas/química , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
Spirotrichilins A (1) and B (2), two novel limonoids with an unprecedented spiro[cyclopenta[b]furan-2,1'-cyclopentan] ring system in A/B/C rings, were isolated from the fruits of trichilia connaroides. Their planar structures and absolute configurations were established based on 1D-, 2D-NMR data, electronic circular dichroism (ECD) exciton chirality method and time-dependent density functional theory (TDDFT)/ECD calculation. A benzilic acid-like rearrangement in ring A was proposed as the key step in the plausible biogenetic pathway of 1 and 2.
Asunto(s)
Limoninas/síntesis química , Meliaceae/química , Compuestos de Espiro/síntesis química , Fenómenos Bioquímicos , Dicroismo Circular , Frutas , Limoninas/química , Espectroscopía de Resonancia Magnética , Estructura Molecular , Compuestos de Espiro/químicaRESUMEN
In the present study, a series of 13-ß-elemene ester derivatives were designed and prepared, and their antioxidant activity was investigated in the H2O2-treated human umbilical vein endothelial cells (HUVECs). Among the test compounds, the dimer compounds 5v and 5w exhibited the most potent antioxidant activity with significant ROS suppression being observed. Both compounds markedly inhibited the H2O2-induced changes in various biochemical substances, such as superoxide dismutase (SOD), malonyldialdehyde (MDA), nitric oxide (NO), and lactic dehydrogenase (LDH), which were superior to that of the positive control vitamin E. Further more, they did not produce any obvious cytotoxicity, but increased the viability of HUVECs injured by H2O2 in a dose-dependent manner. Additionally, compound 5w, designed as a prodrug-like compound, showed improved stability relative to compound 4 in vitro.
Asunto(s)
Antioxidantes/farmacología , Medicamentos Herbarios Chinos/farmacología , Endotelio Vascular/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ácidos Ftálicos/farmacología , Sesquiterpenos/farmacología , Succinatos/farmacología , Antioxidantes/síntesis química , Antioxidantes/metabolismo , Células Cultivadas , Curcuma/química , Estabilidad de Medicamentos , Medicamentos Herbarios Chinos/química , Endotelio Vascular/citología , Endotelio Vascular/metabolismo , Humanos , Peróxido de Hidrógeno/metabolismo , Malondialdehído/metabolismo , Óxido Nítrico/metabolismo , Oxidación-Reducción , Ácidos Ftálicos/síntesis química , Sesquiterpenos/síntesis química , Succinatos/síntesis química , Superóxido Dismutasa/metabolismoRESUMEN
Melicolones A (1) and B (2), a pair of rearranged prenylated acetophenone epimers with an unusual 9-oxatricyclo[3.2.1.1(3,8)]nonane core, were isolated from the leaves of Melicope ptelefolia. Further chiral high-performance liquid chromatography resolution gave enantiomers (+)- and (-)-1, as well as (+)- and (-)-2, respectively. The structures and absolute configurations of the pure enantiomers were determined by extensive spectroscopic data and single crystal X-ray diffraction. All the isolated enantiomers exhibited potent cell protecting activities against high glucose-induced oxidative stress in human vein endothelial cells.
Asunto(s)
Acetofenonas/química , Acetofenonas/aislamiento & purificación , Rutaceae/química , Acetofenonas/farmacología , Alcanos , Cromatografía Líquida de Alta Presión , Cristalografía por Rayos X , Células Endoteliales/efectos de los fármacos , Compuestos Heterocíclicos con 3 Anillos , Humanos , Conformación Molecular , Estructura Molecular , Hojas de la Planta/química , Prenilación , Estereoisomerismo , Difracción de Rayos XRESUMEN
A novel synthetic approach to construct various 3,6-anhydrohexosides via an intramolecular cyclization of corresponding triflates is described. The nucleophilic attack from C3 p-methoxybenzylated hydroxyl to C6 trifluoromethanesulfonate on triflate structures triggered the cyclization reaction to provide 3,6-anhydrohexosides in excellent yields, making the strategy more efficient with respect to the reported protocols. By applying this methodology, a concise first total synthesis of natural product isolated from leaves of Sauropus rostratus was accomplished.
Asunto(s)
Productos Biológicos/síntesis química , Glicósidos/síntesis química , Phyllanthus/química , Productos Biológicos/química , Catálisis , Técnicas Químicas Combinatorias , Cristalografía por Rayos X , Ciclización , Glicósidos/química , Conformación Molecular , Estructura Molecular , Hojas de la Planta/química , EstereoisomerismoRESUMEN
The first synthetic attempt commencing from an eight-membered ring to approach the [5.3.1] bicyclic core of vinigrol has demonstrated the feasibility of using the conformational bias of the cyclooctane-ring system to realize highly diastereoselective reactions. The synthetic potential of the newly disclosed access to in/out isomerism may stimulate broader interests.
Asunto(s)
Compuestos Bicíclicos con Puentes/síntesis química , Química Orgánica/métodos , Diterpenos/síntesis química , Alquilación , Catálisis , Cristalografía por Rayos X , Diterpenos/química , Oxidación-Reducción , Paclitaxel/química , Paladio , EstereoisomerismoRESUMEN
AIM: In a search for new cardiovascular drug candidates, a series of novel oxime ethers derived from a natural isochroman-4-one were synthesized. METHOD: Compounds 3 and 6, derived from the natural antihypertensive compound 7, 8-dihydroxy-3-methyl-isochroman-4-one (XJP), were designed and synthesized. Subsequently, a series of novel isochroman-4-one oxime ether hybrids were prepared by hybridizing various N-substituted isopropanolamine functionalities to isochroman-4-one oxime. Furthermore, ß1-adrenergic blocking activities of the synthesized compounds were assayed using the isolated rat left atria. RESULTS: Twenty target compounds were obtained, and the preliminary structure-activity relationships were deduced. The most promising compound Ic exhibited ß1-adrenoceptor blocking activity (inhibition: 52.2%) at 10(-7) mol·L(-1), which was superior to that of propranolol (inhibition: 49.7%). CONCLUSION: The results suggested that natural product XJP/isopropanolamine moiety hybrids may provide a promising approach for the discovery of novel cardiovascular drug candidates.
Asunto(s)
Antagonistas Adrenérgicos beta/síntesis química , Antagonistas Adrenérgicos beta/farmacología , Benzopiranos/síntesis química , Benzopiranos/farmacología , Medicamentos Herbarios Chinos/síntesis química , Medicamentos Herbarios Chinos/farmacología , Hipertensión/tratamiento farmacológico , Oximas/química , Antagonistas Adrenérgicos beta/química , Animales , Antihipertensivos/síntesis química , Antihipertensivos/química , Antihipertensivos/farmacología , Benzopiranos/química , Medicamentos Herbarios Chinos/química , Humanos , Hipertensión/fisiopatología , Masculino , Estructura Molecular , Ratas , Ratas Sprague-Dawley , Relación Estructura-ActividadRESUMEN
A new series of tacrine-flavonoid hybrids (13a-u) had been designed, synthesized, and evaluated as multifunctional cholinesterase (ChE) inhibitors against Alzheimer's disease (AD). In vitro studies showed that most of the molecules exhibited a significant ability to inhibit ChE and self-induced amyloid-ß (Aß1â42) aggregation. Kinetic and molecular modeling studies also indicated compounds were mixed-type inhibitors, binding simultaneously to active, peripheral and mid-gorge sites of AChE. Particularly, compound 13k was found to be highly potent and showed a balanced inhibitory profile against ChE and self-induced Aß1â42 aggregation. Moreover, it also showed excellent metal chelating property and low cell toxicity. These results suggested that 13k might be an excellent multifunctional agent for AD treatment.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides/antagonistas & inhibidores , Antioxidantes/farmacología , Quelantes/farmacología , Inhibidores de la Colinesterasa/farmacología , Neuroblastoma/tratamiento farmacológico , Compuestos Organometálicos/farmacología , Fragmentos de Péptidos/antagonistas & inhibidores , Enfermedad de Alzheimer/enzimología , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Animales , Antioxidantes/síntesis química , Antioxidantes/química , Compuestos de Bifenilo/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Quelantes/síntesis química , Quelantes/química , Inhibidores de la Colinesterasa/síntesis química , Inhibidores de la Colinesterasa/química , Colinesterasas/metabolismo , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Flavonoides/química , Depuradores de Radicales Libres/química , Humanos , Ratones , Neuroblastoma/patología , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/química , Oxidación-Reducción , Fragmentos de Péptidos/metabolismo , Picratos/química , Relación Estructura-Actividad , Tacrina/químicaRESUMEN
A practical approach to the synthesis of the A, B and C-ring subunit of cyclopamine has been developed. This synthetic tactic highlights the utility of mandelate acetal-mediated resolution of the fused ring ketone (±)-4 and IBX-mediated oxidation cascades from 12 to 9. The availability of advanced intermediates from enantiomerically pure (+)-4 and 2 could provide efficient access to biologically active and structurally diverse C-nor-D-homo-steroidal alkaloids such as cyclopamine.
Asunto(s)
Técnicas de Química Sintética/métodos , Alcaloides de Veratrum/síntesis química , Estructura Molecular , Fenómenos Químicos Orgánicos , Estereoisomerismo , Esteroides/química , Alcaloides de Veratrum/químicaRESUMEN
A series of α-glucosidase inhibitors with the oleanolic acid core and different cinnamic amide ligands were designed and synthesized. Their preliminary structure-activity relationships were analyzed. In general, the compounds with 3,28-disubstituted oleanolic acid exhibited stronger activity than those 28-monosubstituted analogues, and variation of cinnamic amide substitution significantly affected α-glucosidase inhibition activities. Most of the compounds showed potent inhibitory activity against α-glucosidase with much greater efficacy than a typical α-glucosidase inhibitor, acarbose.