| Autor: |
Tshitenge DT; Institute of Organic Chemistry, University of Würzburg , Am Hubland, D-97074 Würzburg, Germany.; Faculty of Pharmaceutical Sciences, University of Kinshasa , B.P. 212, Kinshasa XI, Democratic Republic of the Congo., Feineis D; Institute of Organic Chemistry, University of Würzburg , Am Hubland, D-97074 Würzburg, Germany., Awale S; Division of Natural Drug Discovery, Institute of Natural Medicine, University of Toyama , 2630 Sugitani, Toyama 930-0194, Japan., Bringmann G; Institute of Organic Chemistry, University of Würzburg , Am Hubland, D-97074 Würzburg, Germany. |
| Abstrakt: |
From the tropical plant Gardenia ternifolia Schumach. and Thonn. (Rubiaceae), eight stereoisomeric 2,3-dihydrobenzo[b]furan neolignans, named gardenifolins A-H (1a-d and 2a-d), were isolated and fully structurally characterized. Reversed-phase chromatography of a stem bark extract afforded two peaks, viz. mixtures I and II, each one consisting of two diastereomers and their respective enantiomers. They were resolved and stereochemically analyzed by HPLC on a chiral phase coupled to electronic circular dichroism (ECD) spectroscopy, giving single ECD spectra of all eight stereoisomers. The double-bond geometries (E or Z) of the gardenifolins A-H and their relative configurations (cis or trans) at the stereogenic centers C-7 and C-8 in the dihydrofuran ring system were assigned by 1D and 2D NMR methods, in particular, using NOE difference experiments, whereas the absolute configurations of the isolated enantiomers were established by ECD spectroscopy by applying the reversed helicity rule. The individual pure gardenifolin isomers A-H showed the most different cytotoxic effects against the human cancer HeLa cell line, with 1d and 2a displaying the highest activities, with IC 50 values of 21.0 and 32.5 μM, respectively. Morphological experiments indicated that gardenifolin D (1d) induces apoptosis of HeLa cells at 25 μM. |
