| Autor: |
El-Kashef DH; Institute of Pharmaceutical Biology and Biotechnology, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany.; Department of Pharmacognosy, Faculty of Pharmacy, Minia University, 61519 Minia, Egypt., Obidake DD; Institute of Pharmaceutical Biology and Biotechnology, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany., Schiedlauske K; Institute of Pharmaceutical Biology and Biotechnology, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany., Deipenbrock A; Institute of Pharmaceutical Biology and Biotechnology, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany., Scharf S; Institute of Medical Microbiology and Hospital Hygiene, Medical Faculty, Heinrich Heine University, 40225 Düsseldorf, Germany., Wang H; Hainan Key Laboratory for Research and Development of Natural Products from Li Folk Medicine, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, China., Naumann D; Department of Chemistry and Biochemistry, University of Cologne, 50939 Cologne, Germany., Friedrich D; Department of Chemistry and Biochemistry, University of Cologne, 50939 Cologne, Germany., Miljanovic S; Institute of Pharmaceutical Biology and Biotechnology, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany., Haj Hassani Sohi T; Institute of Inorganic Chemistry and Structural Chemistry, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany., Janiak C; Institute of Inorganic Chemistry and Structural Chemistry, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany., Pfeffer K; Institute of Medical Microbiology and Hospital Hygiene, Medical Faculty, Heinrich Heine University, 40225 Düsseldorf, Germany., Teusch N; Institute of Pharmaceutical Biology and Biotechnology, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany. |
| Abstrakt: |
A new prenylated indole diketopiperazine alkaloid, rubrumline P ( 1 ), was isolated along with six more analogues and characterized from the fermentation culture of a marine sediment-derived fungus, Aspergillus chevalieri , collected at a depth of 15 m near the lighthouse in Dahab, Red Sea, Egypt. In the current study, a bioassay-guided fractionation allowed for the identification of an active fraction displaying significant cytotoxic activity against the human pancreatic adenocarcinoma cell line PANC-1 from the EtOAc extract of the investigated fungus compared to the standard paclitaxel. The structures of the isolated compounds from the active fraction were established using 1D/2D NMR spectroscopy and mass spectrometry, together with comparisons with the literature. The absolute configuration of the obtained indole diketopiperazines was established based on single-crystal X-ray diffraction analyses of rubrumline I ( 2 ) and comparisons of optical rotations and NMR data, as well as on biogenetic considerations. Genome sequencing indicated the formation of prenyltransferases, which was subsequently confirmed by the isolation of mono-, di-, tri-, and tetraprenylated compounds. Compounds rubrumline P ( 1 ) and neoechinulin D ( 4 ) confirmed preferential cytotoxic activity against PANC-1 cancer cells with IC 50 values of 25.8 and 23.4 µM, respectively. Although the underlying mechanism-of-action remains elusive in this study, cell cycle analysis indicated a slight increase in the sub-G1 peak after treatment with compounds 1 and 4 . |
