RESUMEN
Twelve new polyketides, zosteropenillines A-L (1-12), together with known polyketide pallidopenilline A (13), were isolated from the ethylacetate extract of the fungus Penicillium thomii associated with the seagrass Zostera marina. Their structures were established based on spectroscopic methods. The absolute configuration of zosteropenilline A (1) as 4R, 5S, 8S, 9R, 10R, and 13S was determined by a combination of the modified Mosher's method, X-ray analysis, and NOESY data. Absolute configurations of zosteropenillines B-D (2-4) were determined by timedependent density functional theory (TD-DFT) calculations of ECD spectra. The effect of compounds 1-3, 7, 8, 10, and 11 on the viability of human drug-resistant prostate cancer cells PC3 as well as on autophagy in these cancer cells and inhibitory effects of compounds 1, 2, and 8-10 on NO production in LPS-induced RAW 264.7 murine macrophages were examined.
Asunto(s)
Antineoplásicos/farmacología , Organismos Acuáticos/química , Autofagia/efectos de los fármacos , Penicillium/química , Policétidos/farmacología , Animales , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Línea Celular Tumoral , Cristalografía por Rayos X , Humanos , Ratones , Estructura Molecular , Óxido Nítrico/metabolismo , Resonancia Magnética Nuclear Biomolecular , Policétidos/química , Policétidos/aislamiento & purificación , Células RAW 264.7 , Zosteraceae/microbiologíaRESUMEN
Eleven new polyketides, pallidopenillines 1-11, were isolated from the alga-derived fungus Penicillium thomii. The structures of these compounds were established based on spectroscopic methods. The absolute configuration of pallidopenilline A (1) as 4R, 5S, 8S, 9R, 10R, 13R was established using a combination of the modified Mosher's method, X-ray analysis, and NOESY data. The absolute configurations of 2-5 were determined by time-dependent density functional theory calculations of the ECD spectra and ECD and NOESY data. It was shown that 1-acetylpallidopenilline A (2) and pallidopenilline G (10) inhibit the growth of colonies of 22Rv1 cells by 40% at 2 and 1 µM, respectively.
Asunto(s)
Antineoplásicos/aislamiento & purificación , Penicillium/química , Policétidos/aislamiento & purificación , Antineoplásicos/química , Antineoplásicos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Células HCT116 , Humanos , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Policétidos/química , Policétidos/farmacología , Sargassum/microbiologíaRESUMEN
The new 6,6-spiroketal,sargassopenilline H (1), and known peneciraistin C (2) have been isolated from an EtOAc extract of the marine-derived fungus Penicillium lividumKMM 4663. The structure of the new metabolite was determined by HR ESIMS and 1D and 2D NMR spectroscopy. Sargassopenilline H (1) in non-cytotoxic concentration inhibited colony formation of RPMI-7951 and MDA-MB-231 cell lines.
Asunto(s)
Benzopiranos/química , Benzopiranos/farmacología , Penicillium/química , Compuestos de Espiro/química , Compuestos de Espiro/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Estructura MolecularRESUMEN
Seven new 6,6-spiroketals, sargassopenillines A-G (1-7) were isolated from the alga-derived fungi Penicillium thomii KMM 4645 and Penicillium lividum KMM 4663. The structures of these metabolites were determined by HR-MS and 1D and 2D NMR. The absolute configurations of compounds 1, 5 and 6 were assigned by the modified Mosher's method and by CD data. Sargassopenilline C (3) inhibited the transcriptional activity of the oncogenic nuclear factor AP-1 with an IC50 value of 15 µM.
Asunto(s)
Hongos/química , Furanos/química , Furanos/farmacología , Penicillium/química , Phaeophyceae/microbiología , Compuestos de Espiro/química , Compuestos de Espiro/farmacología , Animales , Espectroscopía de Resonancia Magnética/métodos , Ratones , Factor de Transcripción AP-1/metabolismoRESUMEN
Ten new austalide meroterpenoids (1-10) were isolated from the alga-derived fungi Penicillium thomii KMM 4645 and Penicillium lividum KMM 4663. Their structures were elucidated by extensive spectroscopic analysis and by comparison with related known compounds. The absolute configurations of some of the metabolites were assigned by the modified Mosher's method and CD data. Compounds 1, 2, 8, and 9 were able to inhibit AP-1-dependent transcriptional activity in JB6 Cl41 cell lines at noncytotoxic concentrations. Austalides 1-5, 8, and 9 exhibited significant inhibitory activity against endo-1,3-ß-D-glucanase from a crystalline stalk of the marine mollusk Pseudocardium sachalinensis.
