RESUMEN
Our continuing search for marine bioactive secondary metabolites led to the screening of crude extracts of sea cucumbers by the model of Pyricularia oryzae. A new sulfated triterpene glycoside, coloquadranoside A (1), together with four known triterpene glycosides, philinopside A, B, E and pentactaside B (2-5) were isolated from the sea cucumber Colochirus quadrangularis, and their structures were elucidated using extensive spectroscope analysis (ESI-MS, 1D and 2D NMR) and chemical methods. Coloquadranoside A possesses a 16-acetyloxy group in the holostane-type triterpene aglycone with a 7(8)-double bond, a double bond (25,26) at its side chain, and two ß-d-xylose in the carbohydrate chain. Coloquadranoside A exhibits in vitro some antifungus, considerable cytotoxicity (IC50 of 0.46-2.03 µM) against eight human tumor cell lines, in vivo antitumor, and immunomodulatory activity.
Asunto(s)
Antifúngicos/farmacología , Antineoplásicos/farmacología , Glicósidos/química , Inmunomodulación/efectos de los fármacos , Pepinos de Mar/química , Triterpenos/química , Animales , Antifúngicos/química , Antineoplásicos/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Ratones , Ratones Desnudos , Estructura Molecular , Neoplasias Experimentales , Saponinas/químicaRESUMEN
Seven new briarane diterpenoids, gemmacolides AZ-BF (1-7), were isolated together with eight known analogues (8-15) from the South China gorgonian Dichotella gemmacea. Their structures were elucidated based on detailed spectroscopic analysis and a comparison with reported data. In an in vitro bioassay, these compounds exhibited different levels of growth inhibition activity against A549 and MG63 cells, giving continuous evidences about the biological contribution of functional groups at C-2, C-12, C-13, and C-16. These compounds were also evaluated for their antibacterial and antifungal activities. Compound 8 exhibited a potential antibacterial activity against both Gram-positive bacterium Bacillus megaterium and Gram-negative bacterium Escherichia coli.
Asunto(s)
Antozoos/química , Diterpenos/química , Diterpenos/farmacología , Células A549 , Animales , Antibacterianos/química , Antibacterianos/farmacología , Antifúngicos/química , Antifúngicos/farmacología , Bacillus megaterium/efectos de los fármacos , Línea Celular Tumoral , China , Escherichia coli/efectos de los fármacos , HumanosRESUMEN
Five new sesterterpenoids, compounds 1-5, have been isolated from the sponge Hippospongia lachne off Yongxing Island in the South China Sea. The structures of compounds 1-5 were elucidated through extensive spectroscopic analysis, including HRMS, 1D, and 2D NMR experiments. The stereochemistry, including absolute configurations of these compounds, was determined by spectroscopic, chemical, and computational methods. Compounds 1 and 5 showed moderate protein tyrosine phosphatase 1B (PTP1B) inhibitory activities with IC50 values of 5.2 µM and 8.7 µM, respectively, more potent than previously reported hippolides.
Asunto(s)
Inhibidores Enzimáticos/aislamiento & purificación , Poríferos/metabolismo , Proteína Tirosina Fosfatasa no Receptora Tipo 1/antagonistas & inhibidores , Sesterterpenos/farmacología , Animales , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Espectroscopía de Resonancia MagnéticaRESUMEN
Four new triterpene glycosides, variegatusides C-F (1-4), together with three structurally known triterpene glycosides, variegatusides A and B (5, 6), and holothurin B (7), were isolated from the sea cucumber Stichopus variegates Semper (Holothuriidae), collected from the South China Sea. Their structures were elucidated on the basis of extensive spectral analysis (nuclear magnetic resonance (NMR) and electrospray ionization mass spectrometry (ESIMS)) and chemical evidence. Variegatusides C-F exhibit the same structural feature consisting of the presence of a 23-hydroxyl group at the holostane-type triterpene aglycone side chain. Variegatuside C (1) has a double bond (24, 25) in this same chain, while variegatuside D (2) exhibits a 8(9)-ene bond in the holostane-type triterpene aglycone, which has not been extracted from other sea cucumber species. Compound 4 is a native compound from the sea cucumber S. variegates Semper, which has been reported to be desacetylstichloroside B1. Except for holothurin B, these glycosides have no sulfate group in their sugar chain and show potent antifungal activities in vitro biotests.
Asunto(s)
Antifúngicos/farmacología , Glicósidos/farmacología , Stichopus/metabolismo , Triterpenos/farmacología , Animales , Antifúngicos/química , Antifúngicos/aislamiento & purificación , China , Glicósidos/química , Glicósidos/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Espectrometría de Masa por Ionización de Electrospray , Triterpenos/química , Triterpenos/aislamiento & purificaciónRESUMEN
Eighteen new 11,20-epoxy-3Z,5E-dien briaranes, gemmacolides AA-AR (1-18), were isolated together with three known analogs, dichotellides F (19) and I (20), and juncenolide C (21), from the South China Sea gorgonian Dichotella gemmacea. The structures of the compounds were elucidated by detailed spectroscopic analysis and comparison with reported data. The absolute configuration was determined based on the ECD experiment. In the in vitro bioassay, compounds 1-3, 5, 6, 8-12, and 14-19 exhibited different levels of growth inhibition activity against A549 and MG63 cell lines. Preliminary structure-activity analysis suggests that 12-O-isovalerate may increase the activity whereas 13- or 14-O-isovalerate may decrease the activity. Contribution of substitutions at C-2 and C-16 remains uncertain.
Asunto(s)
Antozoos/química , Antineoplásicos/farmacología , Diterpenos/farmacología , Neoplasias/tratamiento farmacológico , Animales , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Línea Celular Tumoral , China , Diterpenos/química , Diterpenos/aislamiento & purificación , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Neoplasias/patología , Océanos y Mares , Análisis Espectral , Relación Estructura-ActividadRESUMEN
Six new briarane diterpenoids, gemmacolides T-Y (1-6), were isolated together with three known analogs, juncenolide J (7), praelolide (8), and junceellolide C (9), from the South China Sea gorgonian Dichotella gemmacea. The structures of the new compounds were elucidated by detailed spectroscopic analysis and comparison with reported data. The absolute configuration was suggested based on biosynthetic considerations. In an in vitro bioassay, compounds 3 and 6 showed potent growth inhibition towards tumor cell lines of A549 and MG63, being stronger than the positive control of adriamycin. These compounds also exhibited weak antimicrobial activity against the bacterium Escherichia coli and the fungi Microbotryum violaceum and Septoria tritici.
Asunto(s)
Antozoos/química , Antiinfecciosos/química , Diterpenos/química , Compuestos Heterocíclicos de 4 o más Anillos/química , Animales , Antiinfecciosos/aislamiento & purificación , Antiinfecciosos/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , China , Diterpenos/aislamiento & purificación , Diterpenos/farmacología , Escherichia coli/efectos de los fármacos , Hongos/efectos de los fármacos , Compuestos Heterocíclicos de 4 o más Anillos/aislamiento & purificación , Compuestos Heterocíclicos de 4 o más Anillos/farmacología , Humanos , Espectroscopía de Resonancia Magnética , Conformación Molecular , Océanos y MaresRESUMEN
Two new alkene sulfates, (5Z)-dec-5-en-1-yl sulfate (4) and (3E)-dec-3-en-1-yl sulfate (5), together with three known sulfated alkanes, 2,6-dimethylheptyl sulfate (1), octyl sulfate (2), and decyl sulfate (3), were isolated from the sea cucumber Apostichopus japonicus. The structures of the new compounds 4 and 5 were elucidated by spectroscopic analysis, including ¹H-, ¹³C-, and 2D-NMR, ESI-MS, and HR-ESI-MS. Compounds 2 and 3 were isolated from natural sources for the first time. In preliminary bioassays in vitro, compounds 4 and 5 showed antibacterial, antifungal, and cytotoxic activities.
Asunto(s)
Alcanos/química , Alquenos/química , Pepinos de Mar/química , Sulfatos/química , Ésteres del Ácido Sulfúrico/química , Alcanos/aislamiento & purificación , Alcanos/farmacología , Alquenos/aislamiento & purificación , Alquenos/farmacología , Animales , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Antifúngicos/química , Antifúngicos/aislamiento & purificación , Antifúngicos/farmacología , Bacillus megaterium/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Conformación Molecular , Ésteres del Ácido Sulfúrico/aislamiento & purificación , Ésteres del Ácido Sulfúrico/farmacologíaRESUMEN
Six new (3Z,5E)-11,20-epoxybriara-3,5-dien-7,18-olide diterpenoids, gemmacolides N-S (1-6), were isolated together with four known analogues, juncenolide D, and juncins R, S and U (7-10), from the South China Sea gorgonian Dichotella gemmacea. The structures of the new compounds were elucidated by the detailed analysis of spectroscopic data in combination with the comparison with reported data. The absolute configuration of 1 was determined by a TDDFT calculation of its solution ECD spectrum, affording the determination of absolute configuration of other analogues by simply comparing their ECD spectra with that of 1. The cytotoxic and antimicrobial activities of these compounds were evaluated. In preliminary in vitro bioassays, compounds 4, 5, 6, 8 and 9 showed cytotoxicity against A549 and MG63, while compounds 1, 2, 4, 7-10 showed antimicrobial activity against the fungus Septoria tritici and the bacterium Escherichia coli.
Asunto(s)
Antozoos/química , Antiinfecciosos/química , Antiinfecciosos/farmacología , Diterpenos/química , Diterpenos/farmacología , Animales , Antiinfecciosos/aislamiento & purificación , Bacterias/efectos de los fármacos , Línea Celular Tumoral , China , Diterpenos/aislamiento & purificación , Hongos/efectos de los fármacos , Humanos , Espectroscopía de Resonancia Magnética/métodos , Modelos Moleculares , Océanos y MaresRESUMEN
Seven new briarane diterpenoids, gemmacolides G-M (1-7), were isolated together with two known analogues, juncin O and junceellolide C, from the South China Sea gorgonian Dichotella gemmacea. The structures of the new compounds were elucidated by detailed analysis of spectroscopic data and comparison with reported data. In an in vitro bioassay, these compounds exhibited different levels of growth inhibition activity against A549 and MG63 cells. In particular, compound 4 was more active than the positive control adriamycin against A549 cells. Compounds 4 and 7 also exhibited weak antimicrobial activity against the bacterium Bacillus megaterium and the fungus Septoria tritici, respectively.
Asunto(s)
Antozoos/química , Antiinfecciosos/aislamiento & purificación , Antineoplásicos/aislamiento & purificación , Diterpenos/aislamiento & purificación , Diterpenos/farmacología , Animales , Antiinfecciosos/química , Antiinfecciosos/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Ascomicetos/efectos de los fármacos , Bacillus megaterium/efectos de los fármacos , Diterpenos/química , Doxorrubicina/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Océanos y MaresRESUMEN
Eight new acyclic manoalide-related sesterterpenes, hippolides A-H (1-8), together with two known manoalide derivatives, (6E)-neomanoalide (9) and (6Z)-neomanoalide (10), were isolated from the South China Sea sponge Hippospongia lachne. The absolute configurations of 1-8 were established by the modified Mosher's method and CD data. Compound 1 exhibited cytotoxicity against A549, HeLa, and HCT-116 cell lines with IC50 values of 5.22×10(-2), 4.80×10(-2), and 9.78 µM, respectively. Compound 1 also showed moderate PTP1B inhibitory activitiy with an IC50 value of 23.81 µM, and compound 2 showed moderate cytotoxicity against the HCT-116 cell line and PTP1B inhibitory activity with IC50 values of 35.13 and 39.67 µM, respectively. In addition, compounds 1 and 5 showed weak anti-inflammatory activity, with IC50 values of 61.97 and 40.35 µM for PKCγ and PKCα, respectively.