RESUMEN
Alzheimer's disease (AD) is a chronic, progressive brain degenerative disease that is common in the elderly. So far, there is no effective treatment. The multi-target-directed ligands (MTDLs) strategy has been recognised as the most promising approach due to the complexity of the pathogenesis of AD. Herein, novel salicylic acid-donepezil-rivastigmine hybrids were designed and synthesised. The bioactivity results exhibited that 5a was a reversible and selective eqBChE inhibitor (IC50 = 0.53 µM), and the docking provided the possible mechanism. Compound 5a also displayed potential anti-inflammatory effects and significant neuroprotective effect. Moreover, 5a exhibited favourable stabilities in artificial gastrointestinal solution and plasma. Finally, 5a demonstrated potential cognitive improvement in scopolamine-induced cognitive dysfunction. Hence, 5a was a potential multifunctional lead compound against AD.
Asunto(s)
Enfermedad de Alzheimer , Fármacos Neuroprotectores , Humanos , Anciano , Donepezilo , Rivastigmina/farmacología , Rivastigmina/uso terapéutico , Enfermedad de Alzheimer/tratamiento farmacológico , Inhibidores de la Colinesterasa/farmacología , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Acetilcolinesterasa/metabolismo , Relación Estructura-ActividadRESUMEN
The fruit of Citrus medica L. var. sarcodactylis Swingle is not only used as a traditional medicinal plant, but also served as a delicious food. Six new (3'â7â³)-biflavonoids (1-6), and twelve known biflavonoid derivatives (7-18) were isolated and characterized from the fruits of C. medica L. var. sarcodactylis Swingle for the first time. Their structures were determined by extensive and comprehensive analyzing NMR, HR-ESI-MS, UV, and IR spectral data coupled with the data described in the literature. Compounds (1-18) were evaluated for their hypolipidemic activities with Orlistat as the positive control, and assayed for their immunosuppressive activities with Dexamethasone as the positive control, respectively. Among them, compounds (1-3) exhibited moderate inhibition of pancreatic lipase activity by inhibiting 68.56 ± 1.40%, 56.18 ± 1.57%, 53.51 ± 1.59% of pancreatic lipase activities at the concentration of 100 µM, respectively. Compounds (4-6) and 8 showed potent immunosuppressive activities with the IC50 values from 16.83 ± 1.32 to 50.90 ± 1.79 µM. The plausible biogenetic pathway and preliminary structure activity relationship of the selected compounds were scientifically summarized and discussed in this study.
Asunto(s)
Biflavonoides/farmacología , Citrus/química , Inhibidores Enzimáticos/farmacología , Hipolipemiantes/farmacología , Inmunosupresores/farmacología , Lipasa/antagonistas & inhibidores , Animales , Biflavonoides/química , Biflavonoides/aislamiento & purificación , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Concanavalina A/antagonistas & inhibidores , Concanavalina A/farmacología , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/aislamiento & purificación , Frutas/química , Células Hep G2 , Humanos , Hipolipemiantes/química , Hipolipemiantes/aislamiento & purificación , Inmunosupresores/química , Inmunosupresores/aislamiento & purificación , Lipasa/metabolismo , Estructura Molecular , Páncreas/enzimología , Bazo/efectos de los fármacos , Relación Estructura-Actividad , PorcinosRESUMEN
The fruit of Citrus medica L. var. sarcodactylis Swingle is a functional food with rich nutrients and medicinal values because of its content of bioactive compounds. A bioactivity-guided chemical investigation from the fruits of C. medica L. var. sarcodactylis Swingle afforded three new benzodioxane neolignans (1-3), three new phenanthrofuran neolignan glycosides (4-6), two new biphenyl-ketone neolignans (7-8), two new 1',7'-bilignan neolignans (9-10), as well as fourteen known neolignan derivatives (11-24), which were isolated and characterized from the fruits of C. medica L. var. sarcodactylis Swingle for the first time. These neolignan derivatives were determined by extensive and comprehensive analyzing NMR, HR-ESI-MS, UV, IR spectral data and compared with the data described in the literature. Among them, compounds 1-3 and 12-13 exhibited moderate hepatoprotective activities to improve the survival rates of HepG2 cells from 46.26 ± 1.90% (APAP, 10 mM) to 67.23 ± 4.25%, 62.87 ± 4.43%, 60.06 ± 6.34%, 56.75 ± 2.30%, 58.35 ± 6.14%, respectively. Additionally, compounds 7-8 and 21-22 displayed moderate neuroprotective activities to raise the survival rates of PC12 cells from 55.30 ± 2.25% to 66.94 ± 3.37%, 70.98 ± 5.05%, 64.64 ± 1.93%, and 62.81 ± 4.11% at 10 µM, respectively. The plausible biogenetic pathway and preliminary structure-activity relationship of the selected compounds were scientifically summarized and discussed in this paper.
Asunto(s)
Citrus/química , Lignanos/química , Sustancias Protectoras/química , Animales , Supervivencia Celular/efectos de los fármacos , Citrus/metabolismo , Frutas/química , Frutas/metabolismo , Células Hep G2 , Humanos , Lignanos/aislamiento & purificación , Lignanos/farmacología , Espectroscopía de Resonancia Magnética , Conformación Molecular , Células PC12 , Sustancias Protectoras/aislamiento & purificación , Sustancias Protectoras/farmacología , Ratas , Relación Estructura-ActividadRESUMEN
Six lignans (1-6) were isolated from salted Aconiti lateralis Radix Praeparata for the first time. These isolates were elucidated as hedyotisol-A (1), (7â³R,8â³R)-8â³-syringaresinol-4â³-hydroxy-3â³,5â³-dimethoxyphenyl-7â³,9â³-propanediol (2), lariciresinol-4-O-ß-d-glucopyranoside (3),(7S,8S)-4-hydroxy-3-methoxy-7,8-(2',1'-O-ß-d-glucopyranosyl)phenyl-propanetriol (4), (+)-isolariciresinol (5), and (+)-lyoniresinol (6) by analyzing extensive and comprehensive spectral data and compared with the data described in the literature, respectively. Compounds (1-6) were evaluated for their neuroprotective activities against corticosterone-induced cell death in PC12 cells with desipramine as the positive control drug. Among them, compounds 1 and 2 showed moderate neuroprotective activities, which increased the survival rates of PC12 cells from 45.50 ± 2.23% to 65.98 ± 1.29%, 58.19 ± 2.94% at 10 µm, respectively.
Asunto(s)
Aconitum/química , Lignanos/aislamiento & purificación , Lignanos/farmacología , Fármacos Neuroprotectores/aislamiento & purificación , Fármacos Neuroprotectores/farmacología , Animales , Muerte Celular/efectos de los fármacos , Células PC12 , RatasRESUMEN
To study phenylpropanoids from Eleocharis dulcis and their hepatoprotective activities. The compounds were separated and purified from ethyl acetate part by conventional column chromatography and preparative liquid chromatography, and their structures were identified by various spectral techniques. The HL-7702 cells damage model of hepatocytes induced by APAP was used to screen and evaluate the hepatoprotective activities of these compounds. Sixteen compounds were isolated from ethyl acetate part of E. dulcis, and their structures were identified as 6'-(4â³-hydroxy-3â³-methoxy-phenylpropenyl)-1-(10-methoxy-phenylacetone)-1'-O-ß-D-glucopy-ranoside(1), susaroyside A(2), clausenaglycoside B(3), clausenaglycoside C(4), clausenaglycoside D(5), emarginone A(6), emarginone B(7), thoreliin B(8), 4-O-(1',3'-dihydroxypropan-2'-yl)-dihydroconiferyl alcohol 9-O-ß-D-glucopyranoside(9), 2-[4-(3-methoxy-1-propenyl)-2-methoxy-phenoxy]-propane-1,3-diol(10), 6'-O-(E-cinnamoyl)-coniferin(11), methyl 3-(2-O-ß-D-glucopyranosyl-3,4,5,6-tetramethoxyphenyl) propanoate(12), clausenaglycoside A(13), 9-O-(E-cinnamoyl)-coniferin(14), 6'-O-(E-cinnamoyl)-syringin(15), 2'-O-(E-cinnamoyl)-syringin(16). Among them, compound 1 was a new compound. Compounds 2-16 were isolated from this plant for the first time. Among them, compounds 2 and 8 showed certain hepatoprotective activities.
Asunto(s)
Eleocharis , Cromatografía , Hepatocitos , Extractos VegetalesRESUMEN
Chinese water chestnut, the bulb of Heleocharis dulcis, has been widely consumed as fruit or vegetable in China since ancient times. It exhibits health-promoting properties that leads to an extensive study of their active components. Successive chromatography of active fragments of H. dulcis resulted in isolation of five new chalcone-flavonone heterodimers (1-3, 6, 9), four new diverse flavonoids (4, 5, 7, 8), and sixteen known flavonoids derivatives (10-25) were elucidated on the basis of their IR, UV, NMR, MS spectrometry data analysis and references from H. dulcis for the first time. Among these isolates, compounds 4, 7, 9, 12, 13, and 17 showed moderate neuroprotective activity, which increased the cell survival rate from 49.23 ± 3.68% for the model to 67.75 ± 2.75%, 57.83 ± 2.46%, 67.98 ± 2.74%, 58.65 ± 3.43%, 56.14 ± 1.99%, and 56.70 ± 1.38% at 10 µM, respectively. Moreover, compounds 1-3, 15, 16, 18, and 20 were found to moderately improve the HepG2 cell survival rates from 39.53% (APAP, 10 mM) to 45.53-53.44%. The outcome of the study provided crucial information regarding the structural diversity and health benefits of the edible bulbs of H. dulcis.
Asunto(s)
Eleocharis/química , Flavonoides/química , Flavonoides/farmacología , Sustancias Protectoras/química , Sustancias Protectoras/farmacología , Animales , Supervivencia Celular/efectos de los fármacos , Citoprotección/efectos de los fármacos , Flavonoides/aislamiento & purificación , Células Hep G2 , Humanos , Hígado/citología , Hígado/efectos de los fármacos , Neuronas/citología , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/aislamiento & purificación , Fármacos Neuroprotectores/farmacología , Células PC12 , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Raíces de Plantas/química , Sustancias Protectoras/aislamiento & purificación , RatasRESUMEN
Parasitic characteristics, mutations and resistance of influenza A virus make it difficult for current influenza antiviral drugs to maintain long-term effectiveness. Currently, to design non-adamantane compounds targeting the S31N mutant of M2 proton channel is a promising direction for the development of novel anti-influenza drugs. In our previous research, a pinanamine-based antiviral M090 was discovered to target hemagglutinin instead of M2, with its structure being highly similar to reported M2-S31N inhibitors. Herein, a series of pinane oxime derivatives were designed from scratch and evaluated for anti-influenza activity and their cytotoxicity in vitro. Utilizing a combination of structure-activity relationship analysis, electrophysiological assay and molecular docking, the most potent compound 11h, as a M2-S31N blocker, exhibited excellent activity with EC50 value at the low micromolar level against both H3N2 and H1N1. No significant toxicity of 11h was observed. In addition, compound 11h was located tightly in the pore of the drug-binding site with the thiophene moiety facing down toward the C-terminus, and did not adopt a similar position and orientation as the reference inhibitor.
Asunto(s)
Antivirales/farmacología , Monoterpenos Bicíclicos/farmacología , Diseño de Fármacos , Virus de la Influenza A/efectos de los fármacos , Oximas/farmacología , Animales , Antivirales/síntesis química , Antivirales/química , Monoterpenos Bicíclicos/síntesis química , Monoterpenos Bicíclicos/química , Perros , Relación Dosis-Respuesta a Droga , Células HEK293 , Humanos , Células de Riñón Canino Madin Darby/efectos de los fármacos , Células de Riñón Canino Madin Darby/virología , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Oximas/síntesis química , Oximas/química , Relación Estructura-ActividadRESUMEN
Four new phenylpropanoid derivatives (1-4), together with eleven known analogues (5-15) were isolated and identified by comparison with their references and extensive spectroscopic methods from Murraya koenigii for the first time. Compounds (1-15) were assayed for their inhibitory activities by measuring IL-6-induced STAT3 promoter activities in HepG2 cells, and found compounds 1, 2, 6, and 15 showed inhibitory effects with IC50 values of 11.5, 18.7, 8.9, and 22.7⯵M, respectively. The inhibitory activities of compounds (1-15) were screened against NO production in lipopolysaccharide (LPS)-induced RAW264.7 macrophage cells, and found compounds 3, 4, 9, 11, and 14 exhibited inhibitions against LPS-induced NO production in RAW264.7 macrophages, with IC50 values of 32.7, 7.9, 42.1, 58.9, and 62.4⯵M, respectively.
Asunto(s)
Murraya/química , Fenilpropionatos/farmacología , Extractos Vegetales/farmacología , Animales , Relación Dosis-Respuesta a Droga , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Conformación Molecular , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Fenilpropionatos/química , Fenilpropionatos/aislamiento & purificación , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Células RAW 264.7 , Relación Estructura-ActividadRESUMEN
In an effort to identify agents from natural products that inhibit protein tyrosine phosphatase 1B (PTP1B), 5 new prenylated stilbenes, (±)-styrastilbene A (1: ), styrastilbene B (2: ), and (±)-styrastilbenes Câ-âE (3, 4: , and 7: ), along with 4 known structurally related compounds (5, 6, 8: , and 9: ), were isolated from the roots of Artocarpus styracifolius. Their structures were elucidated by spectroscopic methods, including 1D and 2D nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass spectrometry (HRESIMS), ultraviolet (UV), and infrared (IR). Based on these isolates, a new plausible biosynthetic pathway for the unusual stilbene derivatives 3: -8: with a tetracyclic ring system is proposed. Among these compounds, 1: -3, 8: , and 9: displayed significant PTP1B inhibitory effects with IC50 values ranging from 2.40 (95% confidence interval [CI]: 2.21â-â2.59) to 8.80 (95% CI: 8.28â-â9.32) µM. Moreover, kinetic analysis and molecular docking simulations were performed to provide insight into the inhibition type as well as the interaction and binding mode of these active isolates with PTP1B. Our results revealed mixed-type PTP1B inhibition for all compounds tested. Docking simulations of these stilbene derivatives showed negative binding energies and close proximity to residues at the allosteric and catalytic sites of PTP1B. These findings suggest that these compounds may have a potential to be further developed as agents for the management of type 2 diabetes mellitus.
Asunto(s)
Artocarpus/química , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores Enzimáticos/farmacología , Simulación del Acoplamiento Molecular , Estructura Molecular , Proteína Tirosina Fosfatasa no Receptora Tipo 1/antagonistas & inhibidores , Estilbenos/farmacología , Raíces de Plantas/química , Prenilación , Estilbenos/químicaRESUMEN
Four new biphenyl derivatives (1-4), along with six known biphenyl derivatives (5-10) were isolated and elucidated by their detailed analyses of spectroscopic data and references from the aerial parts of Oenanthe javanica for the first time. Compounds (1-10) were assayed for their activities about the inhibition of COX-2 enzyme inâ vitro for the first time. Compounds 1, 2, 4, and 6 showed inhibitory activities against COX-2 with IC50 values ranging from 22.18±0.29 to 108.54±0.42â µm.
Asunto(s)
Compuestos de Bifenilo/química , Compuestos de Bifenilo/farmacología , Inhibidores de la Ciclooxigenasa 2/aislamiento & purificación , Inhibidores de la Ciclooxigenasa 2/farmacología , Oenanthe/química , Componentes Aéreos de las Plantas/química , Compuestos de Bifenilo/aislamiento & purificación , Cromatografía Líquida de Alta Presión , Cromatografía en Capa Delgada , Concentración 50 Inhibidora , Estructura Molecular , Análisis Espectral/métodosRESUMEN
Phytochemical investigation of the aerial parts of Pteris cretica led to the isolation and elucidation of nine pterosins, including four new pterosins, creticolacton A (1), 13-hydroxy-2(R),3(R)-pterosin L (2), creticoside A (3), and spelosin 3-O-ß-d-glucopyranoside (4), together with five known pterosins 5-9. Their structures were identified mainly on the basis of 1D and 2D NMR spectral data, ESI-MS and literature comparisons. Compounds 1 and 3 were new type of petrosins with a six membered ring between C-14 and C-15. The new compounds were tested in vitro for their cytotoxic activities against four human tumor cell lines (SH-SY5Y, SGC-7901, HCT-116, Lovo). Results showed that compounds 1 and 2 exhibited cytotoxic activity against HCT-116 cells with IC50 value of 22.4 µM and 15.8 µM, respectively.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Citotoxinas/farmacología , Indanos/farmacología , Pteris/química , Sesquiterpenos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Citotoxinas/química , Citotoxinas/aislamiento & purificación , Células HCT116 , Humanos , Indanos/química , Indanos/aislamiento & purificación , Concentración 50 Inhibidora , Componentes Aéreos de las Plantas/química , Extractos Vegetales/química , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificación , Relación Estructura-ActividadRESUMEN
Phytochemical study of the EtOAc fraction (active extract) of the fruits of Ulmus pumila L. resulted in the isolation of thirteen flavane derivatives, and they were identified by their precise spectral data and literature. All the compounds (1-13) were obtained from the fruits of U. pumila L. for the first time. Meanwhile, the compounds (1-13) were assayed for their hepatoprotective and neuroprotective activities, respectively. Compounds 1, 2, 5, 7 and 8 (10µM) exhibited remarkable hepatoprotective activities, and compounds 9, 10, and 13 showed significant neuroprotective activities with IC50 values of 4.08, 5.34, and 2.02µM, respectively.
Asunto(s)
Frutas/química , Hígado/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Sustancias Protectoras/farmacología , Ulmaceae/química , Ulmus/química , Línea Celular Tumoral , Humanos , Fármacos Neuroprotectores/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Sustancias Protectoras/químicaRESUMEN
Two new carbazole alkaloids 1 and 2, and eleven known congeners 3-13 were isolated and identified from Clausena sanki for the first time. Their structures were elucidated on the basis of extensive UV, IR, MS, NMR spectroscopic data and comparison with literatures. The compounds 1-13 were evaluated by MTT assay to determine whether they decreased VEGF-mediated cell proliferation in HUVECs with Axitinib as positive control. Among them, compounds 1, 2, 6, 8, and 13 (µM) exhibited moderate antiangiogenic activities, which inhibited VEGF-induced HUVEC proliferation in vitro with IC50 values of 12.1 (C.I. 8.2-15.2), 58.1 (C.I. 56.3-63.4), 13.7 (C.I. 9.2-15.4), 16.0 (C.I. 9.5-16.4), and 63.2 (C.I. 57.8-65.7) µM, respectively. Moreover, the antiangiogenic activities of compounds 1-13 were evidenced in vivo in the zebrafish embryo model. As a result, compounds 1, 2, 6, 8, and 13 showed effectively suppress angiogenesis. These research results may guide the search for new natural products with antiangiogenic attributes.
Asunto(s)
Alcaloides/farmacología , Inhibidores de la Angiogénesis/farmacología , Carbazoles/farmacología , Clausena/química , Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Alcaloides/química , Alcaloides/aislamiento & purificación , Inhibidores de la Angiogénesis/química , Inhibidores de la Angiogénesis/aislamiento & purificación , Animales , Carbazoles/química , Carbazoles/aislamiento & purificación , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Estructura Molecular , Relación Estructura-Actividad , Factores de Crecimiento Endotelial Vascular/metabolismo , Pez Cebra/embriologíaRESUMEN
A cobalt/copper-cocatalyzed facile synthesis of imidazo[1,2-a:3,4-a']dipyridiniums from 2H-[1,2'-bipyridin]-2-ones and 2-bromoacetophenones is presented. This strategy provides an alternative to the imidazo[1,2-a:3,4-a']dipyridinium synthesis by employing readily available substrates and a simple procedure, which would render this method potentially useful in organic synthesis.
RESUMEN
A new family of multitarget molecules able to interact with acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), as well as with monoamino oxidase (MAO) A and B, has been synthesized. Novel 3,4-dihydro-2(1H)-quinoline-O-alkylamine derivatives have been designed using a conjunctive approach that combines the JMC49 and donepezil. The most promising compound TM-33 showed potent and balance inhibitory activities toward ChE and MAO (eeAChE, eqBuChE, hMAO-A and hMAO-B with IC50 values of 0.56µM, 2.3µM, 0.3µM and 1.4µM, respectively) but low selectivity. Both kinetic analysis of AChE inhibition and molecular modeling study suggested that TM-33 binds simultaneously to the catalytic active site and peripheral anionic site of AChE. Furthermore, our investigation proved that TM-33 could cross the blood-brain barrier (BBB) in vitro, and abided by Lipinski's rule of five. The results suggest that compound TM-33, an interesting multi-targeted active molecule, offers an attractive starting point for further lead optimization in the drug-discovery process against Alzheimer's disease.
Asunto(s)
Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Monoaminooxidasa/química , Inhibidores de la Monoaminooxidasa/farmacología , Quinolinas/química , Quinolinas/farmacología , Acetilcolinesterasa/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/enzimología , Animales , Barrera Hematoencefálica/metabolismo , Butirilcolinesterasa/metabolismo , Inhibidores de la Colinesterasa/síntesis química , Inhibidores de la Colinesterasa/farmacocinética , Diseño de Fármacos , Electrophorus , Humanos , Monoaminooxidasa/metabolismo , Inhibidores de la Monoaminooxidasa/síntesis química , Inhibidores de la Monoaminooxidasa/farmacocinética , Quinolinas/síntesis química , Quinolinas/farmacocinética , PorcinosRESUMEN
A Cp*CoIII-catalyzed C2-selective C-H alkenylation/annulation cascade transformation of 1-(pyridin-2-yl)-1H-indoles with internal alkynes to afford pyrido[2',1':2,3]pyrimido[1,6-a]indol-5-iums is presented. Moreover, 6,7-dihydro-4H-pyrido[2',1':2,3]pyrimido[1,6-a]indole, a new functionalized N-fused indole core heterocycle, could be constructed effectively via reduction of pyrido[2',1':2,3]pyrimido[1,6-a]indol-5-ium by NaBH4.
RESUMEN
A novel series of ferulic acid-memoquin hybrids were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease (AD). The in vitro studies showed that most of the compounds exhibited a significant ability to inhibit acetylcholinesterase (AChE) (IC50 of 3.2-34.7µM) and self-induced ß-amyloid (Aß1-42) aggregation (30.8-39.1%, 25µM), to act as potential antioxidants (ORAC-FL value of 0.9-1.3). In particular, compound 17d had the greatest ability to inhibit AChE (IC50=3.2µM), and Aß1-42 aggregation (30.8%) was also an excellent antioxidant and neuroprotectant. Moreover, it is capable of disaggregating self-induced Aß aggregation. Furthermore, 17d could cross the blood-brain barrier (BBB) in vitro. The results showed that compound 17d is a potential multifunctional agent for the treatment of AD.
Asunto(s)
Alcanos/farmacología , Enfermedad de Alzheimer/tratamiento farmacológico , Inhibidores de la Colinesterasa/farmacología , Ácidos Cumáricos/farmacología , Etilaminas/farmacología , Fármacos Neuroprotectores/farmacología , Alcanos/química , Péptidos beta-Amiloides/metabolismo , Animales , Antioxidantes/química , Antioxidantes/farmacología , Barrera Hematoencefálica , Técnicas de Química Sintética , Inhibidores de la Colinesterasa/química , Ácidos Cumáricos/química , Diseño de Fármacos , Evaluación Preclínica de Medicamentos/métodos , Etilaminas/química , Humanos , Peróxido de Hidrógeno/farmacología , Fármacos Neuroprotectores/química , Células PC12 , RatasRESUMEN
Four new alkenes (1-4), and six known alkenes (5-12) were isolated from Murraya koenigii (L.) Spreng. Their structures were elucidated on the basis of spectroscopic analyses and references. Compounds (1-12) were evaluated for antioxidative activities. Among them, compounds 1, 2, 4, and 7 exhibited significant antioxidative activities using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay with IC50=21.4-49.5 µM. The known compounds (5-12) were isolated from this plant for the first time.
Asunto(s)
Alquenos/química , Antioxidantes/química , Murraya/química , Extractos Vegetales/química , Alquenos/aislamiento & purificación , Antioxidantes/aislamiento & purificación , Dicroismo Circular , Concentración 50 Inhibidora , Espectroscopía de Resonancia Magnética , Conformación Molecular , Murraya/metabolismo , Hojas de la Planta/química , Hojas de la Planta/metabolismoRESUMEN
Three new phenylpropanoid glycosides 1-3, along with nine known phenylpropanoid glycosides 4-12, were isolated from the aerial parts of Cirsium japonicum. The structures of isolated compounds were elucidated by chemical and spectroscopic methods. Compounds 1, 3, 6, 8, and 11 showed moderate cytotoxicities against MCF-7, U87, HCT116, and A549 cell lines with IC50 values in the range of 1.35-11.32 µM. The known compounds 4-12 were obtained from this plant for the first time.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Cirsium/química , Glicósidos/aislamiento & purificación , Glicósidos/farmacología , Fenilpropionatos/aislamiento & purificación , Fenilpropionatos/farmacología , Antineoplásicos Fitogénicos/química , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Glicósidos/química , Células HCT116 , Humanos , Concentración 50 Inhibidora , Estructura Molecular , Fenilpropionatos/química , Componentes Aéreos de las Plantas/químicaRESUMEN
To investigate the chemical constituents of ethyl acetate from Cirsium setosum, fifteen flavonoids were obtained by column chromatography on silica gel, MCI, Sephadex LH-20, and preparative HPLC. Their structures were identified as 4',5,6-trihydroxy-7-methoxyflavone(1), 4',5-dihydroxy-7,8-dimethoxyflavone(2), sorbifolin-6-O-ß-glucopyranoside(3), kaempferol-7-O-α-L-rhamnoside(4), kaempferol(5), quercetin-3-O-ß-D-glucosyl-7-O-α-L-rhamnoside(6), myricetin(7), myricetin-3-O-ß-D-glucoside(8), 5,7- dihydroxy -3',4'- dimethoxyflavone(9), 3',4',5- trihydroxy-3,7-dimethoxyflavone(10), 3',3,4',5-tetrahydroxy-7-methoxyflavone(11), 3'-hydroxy-4',5,7-trimethoxyflavone(12), 7-hydroxy-3',4',5-trimethoxyflavone(13), 4',5-dihydroxy-2',3',7,8-tetramethoxylflavone(14), and 5-hydroxy-2',3',7,8-tetramethoxylflavone(15) by spectroscopic data analysis. All compounds were isolated from this plant for the first time.Compounds(1-15) were evaluated for their hypoglycemic activities by PTP1B enzyme model. Among them, compounds 2, 12, and 14 showed significant PTP1B inhibitory activities with IC50 values of 2.54, 1.85, 2.11 µmolâ¢L⻹, respectively.