RESUMEN
Three undescribed isosteroidal alkaloids, przewalskines A-C (1-3), as well as seven known alkaloids (4-10) were obtained from Fritillaria przewalskii bulbs. Their structures were deduced by extensive HRESIMS, 1D NMR, and 2D NMR analyses, and their bioactivities were evaluated involving the anti-inflammatory and inhibitory potencies on AChE, BChE, and Aß aggregation. Compound 4 revealed the potent effect on inhibiting Aß aggregation activity with IC50 value of 33.1â µM, AChE activity with IC50 value of 6.9â µM, and also showed NO release inhibitory acitivity with IC50 value of 32.6â µM. These findings contribute new multi-.target anti-AD agents and embody the chemical diversity of F. przewalskii.
Asunto(s)
Alcaloides , Fritillaria , Fritillaria/química , Alcaloides/farmacología , Alcaloides/químicaRESUMEN
Taiwania cryptomerioides Hayata is an endangered relict plant belonging to Taxodiaceae, and it is also an endemic plant to China. The decay-resistant of Taiwania timber can provide highly quality wood for building and furniture. Plenty of regenerative of leaves of T.â cryptomerioides also has been used as a resource for the discovery of new dimeric diterpenoids. In a search for structurally diverse dimeric diterpenoids and potent bioactive isolates, ten new heterodimeric diterpenoids, taiwaniadducts K-T (1-4, 6, 8-11, and 14), along with five known ones (5, 7, 12, 13, and 15), were isolated from the leaves of T.â cryptomerioides. These new compounds were defined by comprehensive spectroscopic analyses, putative biosynthetic pathways, and the values of optical. Biologically, anti-multidrug resistance (MDR) activities of compounds were evaluated. Compounds 4 and 10 exerted a 9.18-fold potentiation effect on bortezmib (BTZ) susceptibility at a tested concentration (20â µM) better than the positive control verapamil. The research of the leaves of T.â cryptomerioides not only added the new data to the structural diversity and activities of dimeric diterpenoids but also could provide support for the medical and industrial application of the leaves of this endangered relict plant.
Asunto(s)
Cupressaceae , Diterpenos , Diterpenos/química , Extractos Vegetales/química , Madera , Análisis Espectral , Cupressaceae/química , Estructura MolecularRESUMEN
Six new Cephalotaxus alkaloids, including five cephalotaxine-type alkaloids, and one homoerythrina-type alkaloid, along with six known analogues, were isolated from the seeds of Cephalotaxus fortunei. Their structures were elucidated by combination of spectroscopic data analyses, time-dependent density functional theory (TDDFT) ECD calculation, and single-crystal X-ray diffraction. Cephalofortine B represents the first example of C-5 epi-cephalotaxine-type alkaloid. All isolated compounds were tested for cytotoxicities against HCT-116, A375, and SK-Mel-28 cell lines. Cephalofortine E showed moderate activity against HCT-116 cell line, with an IC50 value of 7.46 ± 0.77 µM.
Asunto(s)
Alcaloides , Antineoplásicos Fitogénicos , Cephalotaxus , Harringtoninas , Alcaloides/farmacología , Antineoplásicos Fitogénicos/farmacología , Harringtoninas/farmacología , Homoharringtonina , Humanos , Estructura Molecular , SemillasRESUMEN
Fortuneicyclidins A (1) and B (2), a pair of epimeric pyrrolizidine alkaloids containing an unprecedented 7-azatetracyclo[5.4.3.0.02,8]tridecane core, were isolated from the seeds of Cephalotaxus fortunei, along with two biogenetically relative known analogues, 3 and 4. The structures were determined by multiple spectral techniques and chemical derivatization methods. Compound 1 showed inhibitory activity against α-glucosidase.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Cephalotaxus/química , Inhibidores de Glicósido Hidrolasas/farmacología , Hojas de la Planta/química , Alcaloides de Pirrolicidina/farmacología , Alcanos/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , Estructura Molecular , Alcaloides de Pirrolicidina/química , Alcaloides de Pirrolicidina/aislamiento & purificaciónRESUMEN
Taxodisones A and B, C30-terpenes with an unprecedented tetracyclo[12.4.0.0.2,709,14]octodecane core, were isolated from the seeds of Taxodium distichum. Their structures, including their configurations, were unambiguously determined. Their biomimetic synthesis suggests that they stem from diterpenes and monoterpenes, and not from squalene or oxidosqualene. In addition, their bioactivities were also evaluated.
Asunto(s)
Diterpenos/química , Taxodium/química , Biomimética , Catálisis , Complejos de Coordinación/química , Cristalografía por Rayos X , Reacción de Cicloadición , Diterpenos/metabolismo , Erbio/química , Conformación Molecular , Semillas/química , Semillas/metabolismo , Taxodium/metabolismo , Terpenos/química , Terpenos/metabolismoRESUMEN
Two uncommon C37 heterodimeric diterpenoids, taicrypnacids A (1) and B (2), and a known labdane-type diterpenoid (3) were isolated from the leaves of Taiwania cryptomerioides. Several techniques, such as comprehensive spectroscopic analysis, chemical conversion, X-ray crystallography, and ECD data, were employed to define the structures. The two new compounds displayed cytotoxicity against human breast cancer (MCF-7), osteosarcoma (U-2 OS), and human colon carcinoma (HCT-116) cell lines, while the methyl ester 1a showed no activity. Compound 1 induced Ca2+-ROS pathway-mediated endoplasmic reticulum stress, and excessive stress led to cell death by activating apoptosis and autophagy.
Asunto(s)
Cupressaceae/química , Diterpenos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Dimerización , Diterpenos/química , Ensayos de Selección de Medicamentos Antitumorales , Células HCT116 , Humanos , Células MCF-7 , Estructura Molecular , Análisis Espectral/métodos , EstereoisomerismoRESUMEN
Nine new spirocyclic acylphloroglucinol derivatives, hyperpatulols A-I (1-9), were characterized from the flowers of Hypericum patulum. Their structures were elucidated by the basic analysis of the obtained spectroscopic data, and their absolute configurations were assigned by both the electronic circular dichroism (ECD) exciton chirality method and ECD calculation. The evaluation of their anti-migration effects on U2-OS human osteosarcoma cells showed that compound 4 exhibited moderate inhibitory activity in a dose-dependent manner. Further pharmacological studies revealed that 4 could regulate the expression of the proteins Vimentin and E-cadherin.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Flores/química , Hypericum/química , Floroglucinol/farmacología , Compuestos de Espiro/farmacología , Antígenos CD/genética , Antígenos CD/metabolismo , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Cadherinas/genética , Cadherinas/metabolismo , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Estructura Molecular , Floroglucinol/análogos & derivados , Floroglucinol/química , Compuestos de Espiro/química , Compuestos de Espiro/aislamiento & purificación , Relación Estructura-Actividad , Vimentina/genética , Vimentina/metabolismoRESUMEN
Artemisianins A-D (1-4), four stereoisomers of sesquiterpenoid dimers, forming via [4+2] cycloaddition from a 1, 10-seco-guaianolide dienophile and a guaianolide diene, along with two biosynthetically related precurors 5 and 6, were isolated from the famous traditional Chinese medicine Artemisia argyi. The structures of 1-4, including their absolute configurations, were elucidated by extensive spectroscopic data and ECD/TDDFT calculation analysis. Compounds 1-4 exhibited cytotoxicity with IC50 values ranging from 7.2 to 23.3⯵M. The accumulation of Ca2+ in cytoplasm and enlarged endoplasmic reticulum (ER) indicated that 1 mediated HT-29 cancer cell apoptosis through improvement of ER-stress, which was further proved by unfolded protein response (UPR) pathway on basis of the upregulation of IRE1α, p-PERK, ATF6, and CHOP.
Asunto(s)
Apoptosis , Artemisia/química , Estrés del Retículo Endoplásmico , Sesquiterpenos/química , Apoptosis/efectos de los fármacos , Artemisia/metabolismo , Línea Celular Tumoral , Dimerización , Estrés del Retículo Endoplásmico/efectos de los fármacos , Humanos , Medicina Tradicional China , Conformación Molecular , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos/farmacología , EstereoisomerismoRESUMEN
Investigation into the chemical diversity of Artemisia argyi led to the discovery of four new (1-4) and one known (5) guaianolide sesquitenpenoid dimers linked via ester bond, and five other known mono-sesquiterpenoids (6-10). Their structures were determined via extensive spectroscopic data, and the absolute configurations of these compounds were elucidated by calculated ECD analysis and chemical method. The dimeric sesquiterpenoids exhibited NO production inhibitory activity with IC50 values ranging from 7.02 to 32.1⯵M. The studies further suggested that compound 2 inhibited inflammatory responses via suppression of the expression of iNOS, resulting from activation of nuclear factor-kappaB (NF-κB) and phosphorylation of MAPKs (ERK and p38).
Asunto(s)
Artemisia/química , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Óxido Nítrico/metabolismo , Sesquiterpenos de Guayano/química , Animales , China , Quinasas MAP Reguladas por Señal Extracelular , Lactonas/química , Ratones , FN-kappa B/metabolismo , Fosforilación , Hojas de la Planta/química , Células RAW 264.7 , Sesquiterpenos de Guayano/aislamiento & purificación , Proteínas Quinasas p38 Activadas por MitógenosRESUMEN
Biogenesis-inspired chemical research of the leaves of Taiwania cryptomerioides afforded four unprecedented dimeric diterpenes, featuring a tetracyclic [7. 75, 9. 4. 05, 10. 08, 9] octodecane core: taiwanoids A-D (1-4). The structures of these compounds were determined on the basis of comprehensive spectral analysis, chemical conversions and X-ray crystallography. A possible biosynthetic pathway for compounds 1-4 was proposed. Compounds 2 and 3 exerted a 5.37 and 6.26-fold potentiation effect on bortezmib (BTZ) susceptibility at a tested concentration of 20 µM, respectively.
Asunto(s)
Abietanos/química , Cupressaceae/química , Abietanos/farmacología , Antineoplásicos/farmacología , Bortezomib/farmacología , Línea Celular Tumoral , Cristalografía por Rayos X , Dimerización , Resistencia a Antineoplásicos/efectos de los fármacos , Humanos , Modelos Moleculares , Neoplasias/tratamiento farmacológico , Extractos Vegetales/química , Extractos Vegetales/farmacologíaRESUMEN
Ten new withanolides (1-10) and three artificial withanolides (11-13) were isolated from the aerial parts of Tubocapsicum anomalum, together with five known analogues (14-18). Their structures were determined on the basis of extensive spectroscopic and chemical methods. They include seven acnistin-type (1-4, 11, 14 and 15), three withajardin-type (5-7), and eight normal-type (8-10, 12, 13 and 16-18) withanolides. Of normal-type withanolides, a chemical conversion from the 16α,17α-epoxywithanolide (16) to Δ13,14-16α-hydroxywithanolide (18) was achieved by Wagner-Meerwein rearrangement. All isolates were evaluated for their cytotoxicity against four human tumor cell lines (HCT-116, HepG2, MCF-7 and A375). Among them, compounds 1-3, 6-8, 14, 16-18 showed cytotoxic activity with IC50 values of 0.24-8.71⯵M.