RESUMEN
One new cevanine isosteroidal alkaloid named 5,6-anhydrohupehenine (1), together with five known alkaloids (2-6) were isolated from Fritillaria hupehensis Hsiao et K.C.Hsia, among which 5,6-anhydrohupehenine (1) exhibited strong inhibitory activity against HepG2 (IC50 = 12.21 µM) and MCF-7 (IC50 = 22.05 µM) cancer cells. Therefore, a total of 33 5,6-anhydrohupehenine derivatives (9a-9s, 10a-10f, 11a-11b, and 12a-12f) were synthesized and evaluated for their cytotoxic activity. The cytotoxicity evaluation of all 5,6-anhydrohupehenine derivatives against HepG2 and MCF-7 human cancer cells revealed that 9s displayed best activity against HepG2 cells with IC50 at 1.27 µM. Further biological evaluations on 9s showed that it inhibited the proliferation of HepG2 cells and induced apoptosis of the HepG2 cells by activating cleaved caspase-3. Moreover, 9s exhibited strong antimetastatic potential. These results suggest that 5,6-anhydrohupehenine is a promising compound to be designed as novel cytotoxic agents.
Asunto(s)
Alcaloides/farmacología , Antineoplásicos Fitogénicos/farmacología , Citotoxinas/farmacología , Fritillaria/química , Alcaloides/síntesis química , Alcaloides/química , Antineoplásicos Fitogénicos/síntesis química , Antineoplásicos Fitogénicos/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Citotoxinas/síntesis química , Citotoxinas/química , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Conformación Molecular , Relación Estructura-Actividad , Células Tumorales CultivadasRESUMEN
We report on the fabrication of ion exchangeable microstructures by femtosecond laser direct writing of an ion exchange photopolymer, poly(2-acrylamido-2-methyl-1-propanesulfonic acid) (PAMPS). The resultant microstructures are negatively charged in aqueous solution, and can adsorb positively charged species, such as metal ions, nanoparticles, and proteins by electrostatic interaction, forming functional components for chip functionalization. In addition, it is possible to modify the microstructures with positively charged species that make the microstructures sensitive to negatively charged species. As a typical example, a crossed 3D microvessel functionalized with antibodies was fabricated, which reveals great potential for organ-on-a-chip systems. The fabrication of ion exchangeable microstructures holds great promise for flexible chip functionalization.
Asunto(s)
Rayos Láser , Nanotecnología/métodos , Polímeros/química , Ácidos Sulfónicos/química , Escritura , Diseño de EquipoRESUMEN
Shikonin, isolated from the roots of herbal plant Lithospermum erythrorhizon, is a naphthoquinone. It has been reported to exert beneficial anti-inflammatory effects and anti-oxidant properties in various diseases. Isoproterenol (ISO) has been widely used to establish cardiac injury in vivo and in vitro. However, shikonin function in ISO-induced cardiac injury remains uncertain. In our study, we attempted to investigate the efficiency and possible molecular mechanism of shikonin in cardiac injury treatment induced by ISO. In vivo, C57BL6 mice were subcutaneously injected with 5mg/kg ISO to induce heart failure. And mice were given a gavage of shikonin (2 or 4mg/kg/d, for four weeks). Cardiac function, fibrosis indices, inflammation response, apoptosis and endoplasmic reticulum (ER) stress were calculated. Pathological alterations, fibrosis-, inflammation-, apoptosis- and ER stress-related molecules were examined. In ISO-induced cardiac injury, shikonin significantly ameliorated heart function, decreased myocardial fibrosis, suppressed inflammation, attenuated apoptosis and ER stress through impeding collagen accumulation, Toll like receptor 4/nuclear transcription factor κB (TLR4/NF-κB), Caspase-3 and glucose-regulated protein 78 (GRP78) signaling pathways activity, relieving heart failure in vivo. Also, in vitro, shikonin attenuated ISO-induced cardiac muscle cells by reducing fibrosis, inflammation, apoptosis and ER stress. Our findings indicated that shikonin treatment attenuated ISO-induced heart injury, providing an effective therapeutic strategy for heart failure treatment for future.
Asunto(s)
Apoptosis/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Fibrosis/tratamiento farmacológico , Corazón/efectos de los fármacos , Inflamación/tratamiento farmacológico , Naftoquinonas/farmacología , Animales , Cardiomiopatías/tratamiento farmacológico , Cardiomiopatías/metabolismo , Cardiomiopatías/patología , Caspasa 3/metabolismo , Chaperón BiP del Retículo Endoplásmico , Fibrosis/metabolismo , Fibrosis/patología , Regulación de la Expresión Génica/efectos de los fármacos , Proteínas HSP70 de Choque Térmico/metabolismo , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/patología , Inflamación/inducido químicamente , Inflamación/metabolismo , Inflamación/patología , Isoproterenol/efectos adversos , Masculino , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , Miocardio/metabolismo , Miocardio/patología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , FN-kappa B/metabolismoRESUMEN
Continuous investigations of the roots of Aconitum nagarum var. lasiandrum led to the isolation of two new C19-diterpenoid alkaloids, lasiandrine (1) and lasiandroline (2). Their structures were elucidated on the basis of extensive interpretation of spectroscopic and mass spectrometric data.
Asunto(s)
Aconitum/química , Alcaloides Diterpénicos/química , Estructura Molecular , Raíces de Plantas/químicaRESUMEN
Continuous investigations on the whole herbs of Aconitum tanguticum var. trichocarpum led to the isolation of three new C20-diterpenoid alkaloids trichocarpisines A-C (1-3). Their structures were elucidated on the basis of extensive interpretation of the spectroscopic data.
Asunto(s)
Aconitum/química , Alcaloides/química , Diterpenos/química , Extractos Vegetales/química , Alcaloides/aislamiento & purificación , Diterpenos/aislamiento & purificación , Estructura Molecular , Extractos Vegetales/aislamiento & purificación , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
The cardiac effect of thirty-eight diterpenoid alkaloids was evaluated on the isolated bullfrog heart model. Among them, twelve compounds exhibited appreciable cardiac activity, with compounds 3 and 35 being more active than the reference drug lanatoside. The structure-cardiac activity relationships of the diterpenoid alkaloids were summarized based on our present and previous studies [2]: i) 1α-OMe or 1α-OH, 8-OH, 14-OH, and NH (or NMe) are key structural features important for the cardiac effect of the aconitine-type C19-diterpenoid alkaloids without any esters. C18-diterpenoid alkaloids, lycoctonine-type C19-diterpenoid alkaloids, and the veatchine- and denudatine-type C20-diterpenoid alkaloids did not show any cardiac activity; ii) the presence of 3α-OH is beneficial to the cardiac activity; iii) the effect on the cardiac action of 6α-OMe, 13-OH, 15α-OH, and 16-demethoxy or a double bond between C-15 and C-16 depends on the substituent pattern on the nitrogen atom.
Asunto(s)
Alcaloides/farmacología , Fármacos Cardiovasculares/farmacología , Diterpenos/farmacología , Corazón/efectos de los fármacos , Alcaloides/química , Animales , Fármacos Cardiovasculares/química , Diterpenos/química , Estructura Molecular , Rana catesbeiana , Relación Estructura-ActividadRESUMEN
From the whole herb of Delphinium laxicymosum var pilostachyum, three new C20-diterpenoid alkaloids, laxipilostine, laxipilosdine, and laxipilosline (1-3), were isolated, together with fourteen known diterpenoid alkaloids. Their structures were determined by extensively interpretation of their spectroscopic data (1D- and 2D-NMR, MS, and IR).
Asunto(s)
Alcaloides/aislamiento & purificación , Delphinium/química , Diterpenos/aislamiento & purificación , Alcaloides/química , Diterpenos/química , Espectroscopía de Resonancia MagnéticaRESUMEN
Two chlorin derivatives, rhodochlorin dimethyl ester (7) and chlorin-e6 trimethyl ester (8), were prepared from methyl pheophobide a (6) through base-degradation of the E ring and methylation of the carboxylic acids. Full assignments of the 1H, 13C and 15N magnetic resonance spectra of compounds 7 and 8 were made by 2D NMR techniques (1H-1H COSY, 1H-13C HMQC, 1H-13C HMBC, 1H-15N HMBC).
Asunto(s)
Porfirinas/química , Espectroscopía de Resonancia Magnética , Estructura MolecularRESUMEN
Thirty three C19-diterpenoid alkaloids, twenty-two prepared from known C19-diterpenoid alkaloids and eleven isolated from Aconitum and Delphinium spp. were evaluated for their cardiac activity in the isolated bullfrog heart assay. Among them, eleven compounds exhibited cardiac activity, with average rate of amplitude increase in the range of 16-118%. Compound 7, mesaconine (17), hypaconine (25), and beiwutinine (26) exhibited strong cardiac activities relative to the reference drug. The structure-activity relationship data acquired indicated that an alpha-hydroxyl group at C-15, a hydroxyl group at C-8, an alpha-methoxyl or hydroxyl group at C-1, and a secondary amine or N-methyl group in ring A are important structure features necessary for the cardiac activities of the aconitine-type C19-diterpenoid alkaloids without any ester groups. In addition, an alpha-hydroxyl group at C-3 is also helpful for the cardiac activity of these alkaloids.
Asunto(s)
Diterpenos/química , Diterpenos/farmacología , Corazón/efectos de los fármacos , Aconitum/química , Alcaloides/química , Alcaloides/farmacología , Animales , Delphinium/química , Rana catesbeiana , Relación Estructura-ActividadRESUMEN
The relative reactivity of three hydroxyl groups in aconitine toward acetylation, chlorination, sulfonylation, and oxidation has been studied in this paper. The reduction of C-3 ketone and C-15 ketone derivatives of aconitine was also investigated. It was found that (1) the relative reactivity of three hydroxyl groups toward acetylation, chlorination, and sulfonylation is 3-OH>13-OH>>15-OH; (2) 3-OH is much more reactive than 15-OH toward oxidation; and (3) reduction of the carbonyl group at C-3 with NaBH(4) generated a pair of C-3 epimers, while the reduction products of the carbonyl group at C-15 depend largely on the specific reducing agent and the absolute configuration of 16-OCH(3). When the substrate has 16ß-OCH(3), its carbonyl group at C-15 can be reduced with NaBH(4) to yield exclusively the 15α-OH-containing product. Upon replacement of reducing agent NaBH(4) with LiAlH(4), the C-15 carbonyl group can be reduced to yield a pair of C-15 epimers. On the other hand, when the substrate has 16α-OCH(3), C-15 carbonyl group can only be reduced to generate 15α-OH-containing product.
Asunto(s)
Aconitina/química , Radical Hidroxilo/química , Aconitina/farmacología , Cetonas/química , Estructura Molecular , Oxidación-Reducción , EstereoisomerismoRESUMEN
A series of new bisbenzylisoquinoline alkaloids was partially synthesized from tetrandrine and fangchinoline and evaluated for their ability to reverse P-glycoprotein-mediated multidrug resistance (MDR) in cancer cells. All the test compounds increased the intracellular accumulation rate of rhodamine 123 in MDR cells (Bel7402 and HCT8), and most exhibited more potent MDR-reversing activity relative to the reference compound verapamil. Compounds 8, 10, 13, and 14 enhanced intracellular accumulation of doxorubicin in Bel7402 and HCT8 cells.
Asunto(s)
Alcaloides/síntesis química , Alcaloides/farmacología , Bencilisoquinolinas/síntesis química , Bencilisoquinolinas/farmacología , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/efectos de los fármacos , Alcaloides/química , Bencilisoquinolinas/química , Doxorrubicina/farmacología , Humanos , Estructura Molecular , Rodamina 123/análisisRESUMEN
Bioassay-guided fractionation of an n-BuOH extract of the lateral roots of Aconitum carmichaeli. led to the isolation of 5 cardioactive C(19)-diterpenoid alkaloids: N-deethylaconine (1), beiwutinine (2), hypaconine (3), mesaconine (4), and 15α-hydroxyneoline (5). N-Deethylaconine and beiwutinine are new aconitine-type C(19)-diterpenoid alkaloids. Hypaconine was isolated from this species for the first time. Among them, mesaconine, hypaconine, and beiwutinine showed the strongest cardiac actions on the isolated perfused bullfrog heart. Furthermore, mesaconine has protective effects, including improved inotropic effect and left ventricular diastolic function, on myocardial ischemia-reperfusion injury in rat at a dose of 10(-9) mol/L. However, mesaconine has almost no effect on heart rate.
Asunto(s)
Aconitum/química , Alcaloides/química , Cardiotónicos/química , Diterpenos/química , Alcaloides/aislamiento & purificación , Alcaloides/farmacología , Alcaloides/uso terapéutico , Animales , Cardiotónicos/aislamiento & purificación , Cardiotónicos/farmacología , Cardiotónicos/uso terapéutico , Corazón/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Espectroscopía de Resonancia Magnética , Masculino , Conformación Molecular , Raíces de Plantas/química , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/tratamiento farmacológicoRESUMEN
Phytochemical investigation of the leaves of Trichilia connaroides afforded 12 new limonoids with phragmalin- (1-11) and mexicanolide-type skeletons (12). The structures of these limonoids, including the absolute configuration of 3, were determined by spectroscopic analysis. Compounds 6 and 8 showed moderate cytotoxicity against HL-60 cells.
Asunto(s)
Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Medicamentos Herbarios Chinos/aislamiento & purificación , Limoninas/química , Limoninas/aislamiento & purificación , Meliaceae/química , Antineoplásicos Fitogénicos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Células HL-60 , Humanos , Limoninas/farmacología , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Hojas de la Planta/químicaRESUMEN
Eighteen schizandrin A derivatives, possessing an acyl group at 7-OH and/or halogen(s) at C-4 and C-11, were designed and synthesized for evaluation of their in vitro ability to inhibit multidrug resistance (MDR). They exhibit weak ability to restore the intracellular Rhodamine 123 in human hepatocarcinoma MDR cell lines Bel7402 and HCT8 relative to the reference drug verapamil.
Asunto(s)
Ciclooctanos/síntesis química , Ciclooctanos/farmacología , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Lignanos/síntesis química , Lignanos/farmacología , Compuestos Policíclicos/síntesis química , Compuestos Policíclicos/farmacología , Ciclooctanos/química , Humanos , Lignanos/química , Estructura Molecular , Compuestos Policíclicos/química , Rodamina 123/análisis , Schisandra/química , Relación Estructura-ActividadRESUMEN
Two new, rare heteratisine-hetidine-type bisditerpenoid alkaloids designated as trichocarpines A 1 and B 2, together with twelve known compounds have been isolated from the whole plants of Aconitum tanguticum var. trichocarpum. Their structures were elucidated by spectroscopic data interpretation and chemical transformation.
Asunto(s)
Aconitum/química , Alcaloides/química , Diterpenos/química , Alcaloides/aislamiento & purificación , Conformación de Carbohidratos , Diterpenos/aislamiento & purificación , Hidrólisis , Espectroscopía de Resonancia Magnética , Extractos Vegetales/químicaRESUMEN
A new aconitine-type C19-diterpenoid alkaloid, longzhoushansine (1), along with fourteen known alkaloids, were isolated from the roots of Aconitum longzhoushanense. Their structures were established by spectral analysis and chemical methods.
Asunto(s)
Aconitum/química , Alcaloides/química , Diterpenos/química , Estructura Molecular , Raíces de Plantas/químicaRESUMEN
From the whole herbs of Delphinium majus, three new C(19)-diterpenoid alkaloids, majusines A-C (1-3), and six new C(20)-diterpenoid alkaloids, majusimines A-D (4-7) and majusidine A and B (8 and 9), have been isolated, together with 15 known compounds. The structures of compounds 1-9 were elucidated by spectroscopic data interpretation.
Asunto(s)
Delphinium/química , Diterpenos/aislamiento & purificación , Medicamentos Herbarios Chinos/aislamiento & purificación , Plantas Medicinales/química , Alcaloides/química , Diterpenos/química , Medicamentos Herbarios Chinos/química , Estructura Molecular , Resonancia Magnética Nuclear BiomolecularRESUMEN
The aconitine-type alkaloids talatisamine (1), 8,14-diacetyltalatisamine (11), and compound 3, the lycoctonine-type alkaloid deltaline (5), and the 7,17-seco C(19)-diterpenoid alkaloids 7 and 9 were treated with HBr-glacial acetic acid to give useful O-demethylated derivatives 2, 2, 4, 6, 8, and 10 respectively in good to high yields (49-90%).
Asunto(s)
Ácido Acético/química , Alcaloides/química , Diterpenos/química , Ácido Bromhídrico/química , Estructura MolecularRESUMEN
Four new diterpenoid alkaloids: tiantaishansine (1), tiantaishannine (2), tiantaishanmine (3), and tiantaishandine (4) have been isolated from the roots of Delphinium tiantaishan. Their structures were elucidated by chemical evidence and spectral analyses, including ESI-MS, HR-EI-MS, 1D- and 2D-NMR.
Asunto(s)
Alcaloides/química , Alcaloides/aislamiento & purificación , Delphinium/química , Diterpenos/química , Diterpenos/aislamiento & purificación , Raíces de Plantas/química , Resonancia Magnética Nuclear BiomolecularRESUMEN
A new C(19)-diterpenoid alkaloid, ouvrardiantine (1) and two new C(20)-diterpenoid alkaloids, ouvrardiandines A (2) and B (3) were isolated from the root of Aconitum ouvrardianum HAND.-MAZZ. The structure of the new alkaloids was established on the basis of spectral data (1D- and 2D-NMR, HR-MS).