RESUMEN
Chemical investigation of a Korean marine sponge, Monanchora sp., led to the isolation of three new steroids (1-3). Compounds 1 and 2, designated as monanchosterols A and B, respectively, represent the first examples of steroids possessing the bicyclo[4.3.1] A/B ring system from a natural source. Compounds 1-3 were investigated for their anti-inflammatory activity by evaluating their inhibitory effects on the mRNA expression of IL-6, TNF-α, and COX-2 in the LPS-stimulated murine RAW264.7 macrophage cells. Compounds 2 and 3 exhibited significant inhibitory effects on the mRNA expression of IL-6 without notable cytotoxicity to the cells in a dose-dependent manner.
Asunto(s)
Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Compuestos Bicíclicos con Puentes/aislamiento & purificación , Compuestos Bicíclicos con Puentes/farmacología , Poríferos/química , Esteroides/aislamiento & purificación , Animales , Antiinflamatorios/química , Compuestos Bicíclicos con Puentes/química , Ciclooxigenasa 2/metabolismo , Relación Dosis-Respuesta a Droga , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Biología Marina , Ratones , Estructura Molecular , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Resonancia Magnética Nuclear Biomolecular , República de Corea , Esteroides/química , Esteroides/farmacología , Factor de Necrosis Tumoral alfa/efectos de los fármacosRESUMEN
Three new sesterterpenoids, phorbaketals L-N (1-3), were isolated from a marine sponge of the genus Phorbas and their complete structures were elucidated via analysis of HRFABMS and NMR spectroscopic data. Phorbaketal N (3) showed potent cytotoxicity against human pancreas cancer cells (IC50=11.4 µM).
Asunto(s)
Neoplasias Pancreáticas/patología , Poríferos/química , Sesterterpenos/toxicidad , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Estructura Molecular , Sesterterpenos/química , Sesterterpenos/aislamiento & purificación , Relación Estructura-ActividadRESUMEN
Chemical investigation of a Korean marine sponge, Monanchora sp., yielded nine new sesterterpenoids (1-9) along with phorbaketals A-C (10-12). The planar structures were established on the basis of NMR and MS analysis, and the absolute configurations of 1-9 were defined using the modified Mosher's method and CD spectroscopic data analysis. Compounds 1-8, designated as phorbaketals D-K, possess a spiroketal-modified benzopyran moiety such as phorbaketal A, and their structural variations are due to oxidation and/or reduction of the tricyclic core or the side chain. Compound 9, designated as phorbin A, has a monocyclic structure and is proposed to be a possible biogenetic precursor of the phorbaketals. Compounds 1-9 were evaluated for cytotoxicity against four human cancer cell lines (A498, ACHN, MIA-paca, and PANC-1), and a few of them were found to exhibit cytotoxic activity.
Asunto(s)
Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Poríferos/química , Sesterterpenos/aislamiento & purificación , Sesterterpenos/farmacología , Animales , Antineoplásicos/química , Ensayos de Selección de Medicamentos Antitumorales , Furanos/química , Furanos/aislamiento & purificación , Humanos , Corea (Geográfico) , Biología Marina , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Sesterterpenos/química , Compuestos de Espiro/química , Compuestos de Espiro/aislamiento & purificación , EstereoisomerismoRESUMEN
A chemical investigation of a Korean marine sponge, Phorbas sp., yielded unprecedented sesterterpenoids phorone A (1) and isophorbasone A (2) along with ansellone B (3) and phorbasone A acetate (4). Their complete structures were elucidated by the combination of spectroscopic data and chemical manipulation. Phorone A (1) and isophorbasone A (2) have the new "phorane"(5) and "isophorbasane"(6) sesterterpenoid carbon skeletons, respectively. Ansellone B (3) and phorbasone A acetate (4) exhibited potent inhibitory activity on nitric oxide production in RAW 264.7 LPS-activated mouse macrophage cells with IC(50) values of 4.5 and 2.8 µM, respectively.