Gombapyrones, new α-pyrone metabolites produced by Streptomyces griseoruber Acta 3662

Abstract

Gombapyrones A-D, new members of the a-pyrone family of secondary metabolites, were produced by Streptomyces griseoruber Acta 3662, which was isolated from bamboo tree rhizosphere. The strain was characterized by its morphological and chemotaxonomical features and by 16S rDNA sequencing as S. griseobuber. The gombapyrone structures were determined by mass spectrometry and by NMR experiments, and were found to have an inhibitory activity against protein tyrosine phosphatase 1B and glycogen synthase kinase 3b. The Journal Antibiotics ( Keywords: fermentation; isolation; a-pyrone; protein-tyrosine phosphatase inhibitor; Streptomyces; structure elucidation INTRODUCTION In our screening program to detect novel secondary metabolites from actinomycetes for pharmaceutical applications (http://www. actapha rm.org) freshly isolated strains from selected European and Malaysian ecosystems were included. The strains were grown as submerged cultures in different complex media, extracts were prepared from mycelia and from culture filtrates at various fermentation times and were screened by HPLC-diode array analysis to determine their chemical diversity. Evaluation of chromatograms was performed using our in-house developed HPLC-UV-Vis database, which contains 933 entries, most of them being antibiotics. 2 Strain Acta 3662, which was isolated from soil collected from the rhizosphere of bamboo trees in the tropical rainforest of the University of Malaya Field Station at Gombak, Selangor, Malaysia, was of interest because of the presence of a family of metabolites in the mycelium extract having nearly congruent UV-Vis spectra, which were unlike those of all reference compounds of the database. This study describes the taxonomy of the producing strain, the fermentation, isolation, structural elucidation and biological activity of the new family of metabolites from strain Acta 3662, which were named gombapyrones, composed from the collection site Gombak and the a-pyrone scaffold of their structures, which are shown in Figure 1.

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Phylogenetic Identification of Fungi Isolated from the Marine Sponge Tethya aurantium and Identification of Their Secondary Metabolites

“…In addition, cytotoxic activity of cillifuranone (50 μM) towards the human hepatocellular carcinoma cell line HepG2 and the human colon adenocarcinom cell line HT29 were performed according to Schneemann et al [62]. Inhibitory activities of cillifuranone (10 µM) against the enzymes acetylcholinesterase, phosphodiesterase (PDE-4B2), glycogen synthase kinase 3β, protein tyrosin phosphatase 1B, and HIV-1 reverse transcriptase were tested according to Helaly et al [63]. …”

Natural products possessing protein tyrosine phosphatase 1B (PTP1B) inhibitory activity found in the last decades

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