RESUMEN
Octocoral of the genus Clavularia is a kind of marine invertebrate possessing abundant cytotoxic secondary metabolites, such as prostanoids and dolabellanes. In our continuous natural product study of C. spp., two previously undescribed prostanoids [clavulone I-15-one (1) and 12-O-deacetylclavulone I (2)] and eleven known analogs (3-13) were identified. The structures of these new compounds were elucidated based on analysis of their 1D and 2D NMR, HRESIMS, and IR data. Additionally, all tested prostanoids (1 and 3-13) showed potent cytotoxic activities against the human oral cancer cell line (Ca9-22). The major compound 3 showed cytotoxic activity against the Ca9-22 cells with the IC50 value of 2.11 ± 0.03 µg/mL, which echoes the cytotoxic effect of the coral extract. In addition, in silico tools were used to predict the possible effects of isolated compounds on human tumor cell lines and nitric oxide production, as well as the pharmacological potentials.
Asunto(s)
Antozoos , Antineoplásicos , Prostaglandinas , Humanos , Antozoos/química , Animales , Línea Celular Tumoral , Prostaglandinas/farmacología , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Óxido Nítrico/metabolismo , Concentración 50 Inhibidora , Organismos Acuáticos , Estructura MolecularRESUMEN
Five new eudensamane-type sesquiterpene lactones, clasamanes A-E (1-5), three new dolabellane-type diterpenes, clabellanes A-C (6-8), and fifteen known compounds (9-23) were isolated from the ethanolic extract of Taiwanese soft coral Clavularia spp. The structures of all undescribed components (1-8) were determined by analysis of IR, mass, NMR, and UV spectroscopic data. The absolute configuration of new compounds was determined by using circular dichroism and DP4+ calculations. The cytotoxic activities of all isolated marine natural products were evaluated. Compound 7 showed a significant cytotoxic effect against oral cancer cell line (Ca9-22) with an IC50 value of 7.26 ± 0.17 µg/mL.
Asunto(s)
Antozoos , Antineoplásicos , Diterpenos , Neoplasias de la Boca , Animales , Antozoos/química , Antineoplásicos/farmacología , Antineoplásicos/química , Células Tumorales Cultivadas , Espectroscopía de Resonancia Magnética , Neoplasias de la Boca/tratamiento farmacológico , Estructura Molecular , Diterpenos/farmacología , Diterpenos/químicaRESUMEN
Application of LC-MS/MS-based molecular networking indicated the ethanol extract of octocoral Asterospicularia laurae is a potential source for the discovery of new xenicane derivatives. A natural product investigation of this soft coral resulted in the isolation of four new xenicane diterpenoids, asterolaurins OâR (1â4), together with six known compounds, xeniolide-A (5), isoxeniolide-A (6), xeniolide-B (7), 7,8-epoxyxeniolide-B (8), 7,8-oxido-isoxeniolide-A (9), and 9-hydroxyxeniolide-F (10). The structures of isolated compounds were characterized by employing spectroscopic analyses, including 2D-NMR (COSY, HMQC, HMBC, and NOESY) and high-resolution electrospray ionization mass spectrometry (HRESIMS). Asterolaurin O is the first case of brominated tricarbocyclic type floridicin in the family Xeniidae. Concerning bioactivity, the cytotoxic activity of those isolates was evaluated. As a result, compounds 1 and 2 demonstrated a selective cytotoxic effect against the MCF-7 cell line at IC50 of 14.7 and 25.1 µM, respectively.
Asunto(s)
Antozoos/química , Antineoplásicos/aislamiento & purificación , Diterpenos/aislamiento & purificación , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Cromatografía Liquida , Diterpenos/química , Diterpenos/farmacología , Humanos , Concentración 50 Inhibidora , Células MCF-7 , Taiwán , Espectrometría de Masas en TándemRESUMEN
Plants of the genus Callicarpa are known to possess several medicinal effects. The constituents of the Taiwan endemic plant Callicarpa hypoleucophylla have never been studied. Therefore, C. hypoleucophylla was selected for our phytochemical investigation. Two new clerodane-type diterpenoids, named callihypolins A (1) and B (2), along with seven known compounds were isolated from the leaves and twigs of the Lamiaceae plant C. hypoleucophylla and then characterized. The structures of compounds 1 and 2 were elucidated by spectroscopic data analysis, specifically, two-dimension nuclear magnetic resonance (NMR). The anti-inflammatory activity of compounds 1-9 based on the suppression of superoxide anion generation and elastase release was evaluated. Among the isolates, compounds 2-4 showed anti-inflammatory activity (9.52-32.48% inhibition at the concentration 10 µm) by suppressing superoxide anion generation and elastase release. Our findings not only expand the description of the structural diversity of the compounds present in plants of the genus Callicarpa but also highlight the possibility of developing anti-inflammatory agents from Callicarpa endemic species.
Asunto(s)
Antiinflamatorios , Callicarpa/química , Diterpenos de Tipo Clerodano , Neutrófilos/metabolismo , Adulto , Antiinflamatorios/química , Antiinflamatorios/farmacología , Diterpenos de Tipo Clerodano/química , Diterpenos de Tipo Clerodano/farmacología , Femenino , Humanos , Masculino , Neutrófilos/patología , Superóxidos/metabolismoRESUMEN
Phytochemical investigation of the flowers of Acmella oleracea had resulted in the isolation of one new alkylamide, (2E,5Z)-N-isobutylundeca-2,5-diene-8,10-diynamide (1), together with four known analogues (2-5). The structures of these compounds were determined by the interpretation of spectroscopic methods, especially NMR technologies (COSY, HSQC, HMBC, and NOESY). In addition, a convenient method for concentrating the alkylamide-rich fraction and analyzing fingerprint profile of A. oleracea was established.
Asunto(s)
Amidas/química , Asteraceae/química , Extractos Vegetales/química , Flores/química , Estructura MolecularRESUMEN
Antiproliferation effects of Clavularia-derived natural products against cancer cells have been reported on, but most studies have focused on identifying bioactive compounds, lacking a detailed investigation of the molecular mechanism. Crude extracts generally exhibit multiple targeting potentials for anticancer effects, but they have rarely been assessed for methanol extracts of Clavularia inflata (MECI). This investigation aims to evaluate the antiproliferation of MECI and to examine several potential mechanisms between oral cancer and normal cells. A 24 h MTS assay demonstrated that MECI decreased cell viability in several oral cancer cell lines more than in normal cells. N-acetylcysteine (NAC), an oxidative stress inhibitor, recovered these antiproliferation effects. Higher oxidative stress was stimulated by MECI in oral cancer cells than in normal cells, as proven by examining reactive oxygen species and mitochondrial superoxide. This preferential induction of oxidative stress was partly explained by downregulating more cellular antioxidants, such as glutathione, in oral cancer cells than in normal cells. Consequently, the MECI-generated high oxidative stress in oral cancer cells was preferred to trigger more subG1 population, apoptosis expression (annexin V and caspase activation), and DNA damage, reverted by NAC. In conclusion, MECI is a potent marine natural product showing preferential antiproliferation against oral cancer cells.
RESUMEN
Chemical investigation of the EtOH extract of the soft coral Cespitularia taeniata May collected in Taiwan has resulted in the isolation of two new sesquiterpene lactams, taenialactams A and B (1 and 2, resp.), and a new sesquiterpene lactone, taenialactone A (3), together with 8beta-methoxyatractylenolide (4) and atractylenolactam (5). The structures of these compounds were determined on the basis of spectroscopic analyses. The in vitro cytotoxic activities of the isolated metabolites were tested against KB, Daoy, and WiDr cell lines. A biogenetic pathway for these novel compounds was proposed.
Asunto(s)
Antozoos/química , Antineoplásicos/farmacología , Sesquiterpenos/farmacología , Animales , Antineoplásicos/química , Línea Celular Tumoral , Células HL-60 , Humanos , Células KB , Resonancia Magnética Nuclear Biomolecular , Sesquiterpenos/químicaRESUMEN
Phytochemical investigation of the ethanolic extract of Grangea maderaspatana led to isolation of gramaderins A-D, together with thirteen known compounds. All isolates were assayed for their anti-inflammatory activities. Consequently, 5,7-dihydroxy-3,6,3',4',5'-pentamethoxyflavone and 5,3'-dihydroxy-3,6,7,4',5'-pentamethoxyflavone showed significant bioactivities by inhibiting superoxide anion generation. 8-Acetoxy-pentadeca-1,9Z,14-trien-4,6-diyne-3-ol also demonstrated potent inhibition on elastase release. The gramaderins A/C (ß-alkyl linked γ-lactone) and gramaderins B/D (α-alkyl linked γ-lactone) co-exist in this plant material, of which the latter derivatives are few in nature. Gramaderins C/D possess a special linear dilactone diterpene skeleton, which never been reported.
Asunto(s)
Antiinflamatorios no Esteroideos/aislamiento & purificación , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios/aislamiento & purificación , Asteraceae/química , Diterpenos/aislamiento & purificación , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antiinflamatorios no Esteroideos/química , Diterpenos/química , Diterpenos/farmacología , Flavonas/química , Lactonas/química , Estructura MolecularRESUMEN
Mana-Hox is a synthetic analog of manzamines, which are beta-carboline alkaloids isolated from marine sponges. Mana-Hox exhibited cytotoxicity against various tumor cell lines with the IC(50) range from 1 to 5 microM. Cell cycle synchronization and flow cytometric analysis showed that Mana-Hox delayed cell cycle progression at mitosis. At the concentration that delayed mitotic progression, bipolar spindle with lagged chromosomes and multipolar spindle with disorganized chromosomes were detected. The presence of such aberrant mitotic cells accompanied by the activation of spindle checkpoint that delayed cells exit from mitosis. However, after a short delay, lagged chromosomes were able to display in the abnormal metaphase plates, and subsequent cell division resulting in chromosome missegregation. Furthermore, the aberrant mitotic cells showed lower viability, indicating that Mana-Hox-induced cell death resulting from chromosome missegregation. This study is the first to explore cytotoxic mechanism of a manzamine-related compound and understand its potential as a lead compound for the development of future anticancer agents.
Asunto(s)
Alcaloides/química , Alcaloides/toxicidad , Carbolinas/química , Carbolinas/toxicidad , Citotoxinas/química , Citotoxinas/toxicidad , Indoles/química , Pirroles/química , Carbazoles , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Cromosomas Humanos/efectos de los fármacos , Humanos , Concentración 50 Inhibidora , Microtúbulos/efectos de los fármacos , Microtúbulos/metabolismo , Nocodazol/farmacología , Huso Acromático/efectos de los fármacosRESUMEN
A series of 1-substituted 1,2,3,4-tetrahydro- and 3,4-dihydro-beta-carboline derivatives have been synthesized and evaluated for antitumor activity against murine P-388 and human tumor cell lines, KB-16, A-549 and HT-29. All of the compounds prepared, except for 19, showed significant cytotoxicity. Among them, compound 29 exhibited the most potent activity against all tested tumor cell lines. There was an apparent lack of correlation regarding cytotoxicity between 1,2,3,4-tetrahydro- and 3,4-dihydro-beta-carbolines. This study is the first to discover compound 29 as a potential lead for the development of future anticancer agents. The mode of inhibition for compound 29 was proposed.
Asunto(s)
Antineoplásicos/síntesis química , Carbolinas/síntesis química , Antineoplásicos/farmacología , Carbolinas/farmacología , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales/métodos , HumanosRESUMEN
Five new taxane diterpenoids, taxumairols G (1), H (2), I (3), J (4), and L (5) were isolated from extracts of the roots of Taiwanese Taxus mairei (LEMEE & LEVL.) S. Y. Hu. Compounds 1-4 belong to the new 11(15-->1)-abeo-taxene system, having a tetrahydrofuran ring along carbons C-2, C-3, C-4 and C-20. Compounds 3 and 4 contain an isopropenyl group at C-1 while compounds 1 and 2 are attached with a benzoxyl group at C-15. The structures of compounds 1-5 were determined on the basis of two-dimensional (2D)-NMR techniques including correlation spectroscopy (COSY), heteronuclear single quantum coherence (HSQC), heteronuclear multiple bond correlation (HMBC), and nuclear Overhauser effect spectroscopy (NOESY) experiments.
Asunto(s)
Hidrocarburos Aromáticos con Puentes/aislamiento & purificación , Diterpenos/aislamiento & purificación , Taxoides , Taxus/química , Hidrocarburos Aromáticos con Puentes/química , Diterpenos/química , Raíces de Plantas/química , TaiwánRESUMEN
In addition to 19-dydroxybaccatin III, 1beta-hydroxy-5 alpha-deacetylbaccatin I, taxayuntin G and 13-O-deacetyltaxumairol Z (4), three new taxane diterpenoids, taxumairols X (1), Y (2), Z (3) have been isolated from extracts of the Formosan Taxus mairei (LEMEE & LEVL.) S. Y. HU. Compounds 1-2 belong to the 11(15-->1)-abeo-taxane system, having a tetrahydrofuran ring at C-2, C-3, C-4 and C-20. The new compound 3 and 4, which was misidentified previously are derivatives of 11(15-->1)-abeo-taxane with an intact oxirane system. The structures of compounds 1-4 were elucidated on the basis of extensive two dimensional (2D)-NMR analysis.