RESUMEN
A short scalable biomimetic route to bioactive natural product bimagnolignan (1) was accomplished. Compound 1 was successfully prepared through a three-step metal-free synthesis from honokiol (2). Alternatively, 1 was also synthesized by biomimetic transformations that mimic tyrosinase in four steps. The key reactions feature a regioselective acetylation, a highly efficient C(sp2)-H oxidation, a cascade aerobic oxidative cyclization/coupling, and a Cu-catalyzed direct oxidative coupling. In addition, cell-based assays validate that 1 is a promising natural lead for HER2-positive breast cancer treatment.
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Biomimética , Neoplasias de la Mama , Humanos , Femenino , Ciclización , Oxidación-Reducción , Acoplamiento Oxidativo , Neoplasias de la Mama/tratamiento farmacológicoRESUMEN
The strategies or drugs for preventing and treating Hyperuricemia (HUA) are still lacking. As a traditional Chinese medicine (TCM) with a profound history, Ampelopsis grossedentata has been shown to play diverse biological roles. The purpose of the present study was to evaluate hypouricemic effect of A. grossedentata, and investigate its involved material basis and mechanism. A HUA mice model was established to evaluate the therapeutic effects of A. grossedentata. And then some extracts from A. grossedentata were prepared, isolated and analyzed. Furthermore, network pharmacology, based on the above results, was used to discover potential active ingredients and therapeutic targets, and they were further verified and explored by molecular docking and in vitro experiments. In vivo experiments showed that A. grossedentata exerted hypouricemic effect on mice of HUA. The core active ingredients (quercetin, myricetin and dihydromyricetin etc.) and core targets (PTGS2, XOD and ABCG2 etc.) for A. grossedentata to treat HUA were predicted by network pharmacology. And molecular docking showed that the spontaneous binding activities of above components and targets were marvelous. In vitro experiments further demonstrated that A. grossedentata exerted hypouricemic effect by decreasing the levels of UA, XOD, antioxidant factors, inflammatory factors, GLUT9 and URAT1 in HK-2 cells of HUA. Taken together, this study integrates multi-level interaction network with in vivo/vitro experiments to systematically reveal the material basis and mechanism of A. grossedentata in treating HUA, which provides a scientific basis for further study of A. grossedentata and HUA.
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Ampelopsis , Hiperuricemia , Ratones , Animales , Hiperuricemia/tratamiento farmacológico , Ampelopsis/química , Simulación del Acoplamiento Molecular , Estructura Molecular , Antioxidantes/farmacologíaRESUMEN
The bark of Streblus indicus, a Dai medicine in China, has been listed in the Chinese Materia Medica as possessing hemostatic and analgesic properties. Ethnic medicine books record that its bark or leaves for the treatment of mumps and lymphoma. However, according to the literature survey, anti-inflammatory and analgesic studies available for leaves and branches of S. indicus have been seldom reported so far. The current study focuses on the metabolites of S. indicus bark and leaves responsible for anti-inflammatory and analgesic effects on the basis of bioactive-included acetic acid writhing, hot-plate, and xylene-induced ear swelling. The secretion of inflammatory mediators, TNF-α, IL-6, IL-1ß, IL-4, and IL-10, were evaluated for their anti-inflammatory by xylene-induced in mouse ear cells. Histological examination was used to assess the anti-inflammatory and analgesic effects of the branches and leaves of S. indicus, and Western blot analysis determined the mechanism of the methanolic extract of branches and leaves. Different metabolites of S. indicus significantly alleviated analgesic and anti-inflammatory effects, with no discernable differences among them. All metabolites decreased the levels of TNF-α, IL-1ß, and IL-6 and increased the levels of IL-4 and IL-10. The analgesic and anti-inflammatory mechanism of the methanolic extract was related to the NF-kB signaling pathway. These results not only would account for scientific knowledge for the traditional application of S. indicus, but also provide a credible theoretical foundation for the further development of anti-inflammatory and analgesic agents.
RESUMEN
Gentiana scabra, a famous traditional Chinese medicine (TCM), has been documented in Chinese Pharmacopoeia for the treatment of hepatitis. Its index component gentiopicroside could not be detected in the decoction, which suggested that the quality control of the TCM with this ingredient needs attention. The transformed products were obtained from gentiopicroside, mimicking the traditional process of G. scabra. Further investigation of the heat-transformed products yielded two secoiridoid dimers, gentiovarisin A (1) and B (2), with an unprecedented 6/6/6/6/6-fused pentacyclic skeletons. Their structures were elucidated by extensive spectroscopic analyses and single-crystal X-ray diffraction analysis, and the absolute configurations of 1 were confirmed as (+)-1 and (-)-1 by ECD method. Plausible transformation pathways of the isolates were also proposed. Compounds 1 and 2 exhibited in vitro hepatoprotective activity similar to gentiopicroside, while (+)-1 displayed a more potent hepatoprotective activity than N-Acetyl-L-cysteine.
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Medicamentos Herbarios Chinos , Gentiana , Estructura Molecular , Glucósidos Iridoides/farmacología , Glucósidos Iridoides/química , Gentiana/química , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/químicaRESUMEN
(±)-Involucrasin C (1), a pair of new 2,3-dihydro-1H-indene enantiomers, along with an enantiomeric analog (2), were isolated from Shuteria involucrata. Their structures were established by the basis of comprehensive spectroscopic data analysis and X-ray crystallographic diffraction. Both 1 and 2 significantly inhibited the secretion of pro-inflammatory cytokines IL-6, TNF-α, and IL-1ß, suggesting that these two natural 2,3-dihydro-1H-indene derivatives may be active components of S.â involucrata and may block inflammation in the initial stage.
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Indenos , Factor de Necrosis Tumoral alfa , Antiinflamatorios/química , Antiinflamatorios/farmacología , China , Citocinas , Indenos/química , Interleucina-6RESUMEN
(±)-Involucrasins A (1) and B (2), two pairs of flavanone enantiomers were isolated from Shuteria involucrata. Structurally, both 1 and 2 are rare representatives of 5-dehydroxy/5-demethoxy 2',3',4'-trisubstituted flavanones. Their structures were elucidated on the basis of comprehensive spectroscopic data analysis and comparison with the literature data. Involucrasin B (2) exhibited moderate anti-proliferative activity against Caco-2, MCF-7, MDA-MB-468, and HCT116 cell lines with IC50 values ranging from 7.9-22.7 µM. Involucrasin A (1) exhibited weak inhibitory activity against Caco-2 and MCF-7 cell lines with IC50 values of 25.8 and 26.5 µM, respectively.
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Flavanonas , Neoplasias , Células CACO-2 , Línea Celular Tumoral , Proliferación Celular , Flavanonas/química , Flavanonas/farmacología , Humanos , Concentración 50 Inhibidora , Estructura MolecularRESUMEN
Swertia mileensis, known as Qing-Ye-Dan (QYD), has been documented in Chinese Pharmacopoeia to cure hepatitis. Interestingly, its announced main active component, swertiamarin, could not be detected in the decoction, which indicated that the efficacy of QYD might be attributed to heat-transformed products of swertiamarin (HTPS). Further investigation on HTPS led to the isolation of sweritranslactone D (1), a novel secoiridoid dimer possessing a tetracyclic lactone skeleton, with better hepatoprotective activity than N-acetyl-L-cysteine in vitro.
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Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Calor , Glucósidos Iridoides/química , Lactonas/química , Sustancias Protectoras/farmacología , Pironas/química , Animales , Línea Celular , Medicamentos Herbarios Chinos , Humanos , Ratones , Estructura Molecular , Sustancias Protectoras/aislamiento & purificación , Swertia/químicaRESUMEN
Skeleton-diversity-oriented chemical conversion from pure natural products is a valuable method to obtain natural product-like compounds, especially those with novel architecture. The application of phytochemical methods to iridoids yielded three novel secoiridoid dimers: sweritranslactones A-C (1-3). These molecules possess a 6/6/6/6/6/6-fused hexacyclic skeleton and were obtained from swertiamarin, one of the major constituents of the genus Swertia, via a [4 + 2] cycloaddition and intramolecular nucleophilic addition under aqueous conditions. The structures were established based on extensive spectroscopic characterization and X-ray crystallographic diffraction analysis.
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Glucósidos Iridoides/química , Iridoides/química , Pironas/química , Cristalografía por Rayos X , Reacción de Cicloadición , Dimerización , Estructura MolecularRESUMEN
Aconitum vilmorinianum Komarov is a local medicinal plant used in many well-known clinical preparations to treat rheumatism and pains in Yunnan Province, China. Phytochemical examination of the roots of A. vilmorinianum led to the isolation of three novel imine-type norditerpenoid alkaloids named vilmorrianines E-G (1-3), and a new natural alkaloid N-desethyl-N-formyl-8-O-methyltalatisamine (4), together with 14 known alkaloids. Their structures were elucidated on the basis of spectroscopic evidence. Vilmorrianine E is the first known norditerpenoid alkaloid containing both an imine group and a three-membered ring formed by C8, C9, and C10.
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Aconitum/química , Alcaloides/química , Diterpenos/química , Plantas Medicinales/químicaRESUMEN
OBJECTIVE: To investigate the chemical constituents of the processed products of Aconitum Vilmorinian Radix. METHODS: The constituents were isolated by repeated column chromatography over silica gel, alumina and RP-C18 as well as recrystallization. The structures were elucidated on the basis of spectral analysis and physicochemical properties. RESULTS: Ten compounds were obtained from the methanol extract, and they were identified as yunaconitine (1), 8-deacetyl-yunaconitine (2), geniculatine C (3), vilmorrianine B (4), vilmorrianine C(5), vilmorrianine D (6), talatisamine (7), ß-sitosterol (8), ß-daucosterol (9) and ß-sitosterol acetate (10). CONCLUSION: All compounds are obtained from the processed products of Aconitum Vilmoriniani Radix for the first time.
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Aconitum/química , Fitoquímicos/análisis , Raíces de Plantas/química , Aconitina/análogos & derivados , SitoesterolesRESUMEN
OBJECTIVE: To study the chemical constituents of chloroform fraction from Aconitum bulleyanum. METHODS: The compounds were isolated by various chromatographic techniques and identified by spectroscopic methods. RESULTS: 7 compounds were obtained and identified as yunaconitine (1), crassicaudine (2), foresaconitine (3), chasmaconitine (4), bulleyaconitine A (5), franchetine (6), and beta-sitosterol (7), CONCLUSION: Compounds 2-7 are isolated from this plant for the first time.