2-Pyrone natural products and mimetics: isolation, characterisation and biological activity

McGlacken, Gerard P.; Fairlamb, Ian J. S.

doi:10.1039/b416651p

Cited by 320 publications

(170 citation statements)

References 196 publications

(156 reference statements)

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“…8 They exhibit a wide range of biological activities, such as antifungal, cytotoxic, neurotoxic and phytotoxic properties, and treatment of Alzheimer's disease and high cholesterol is discussed. 8,9,10 Furthermore, 4-hydroxy-2-pyrones have become one of the most important classes of anti-human immunodeficiency virus (HIV) agents in recent years. 8 These non-peptide compounds seem to be promising candidates for the treatment of AIDS.…”

Section: S Helaly Et Almentioning

confidence: 99%

“…8,9,10 Furthermore, 4-hydroxy-2-pyrones have become one of the most important classes of anti-human immunodeficiency virus (HIV) agents in recent years. 8 These non-peptide compounds seem to be promising candidates for the treatment of AIDS. In comparison with peptides, small a-pyrones are interesting lead candidates for synthetic strategies because of their lack of chiral centers.…”

Section: S Helaly Et Almentioning

confidence: 99%

“…In comparison with peptides, small a-pyrones are interesting lead candidates for synthetic strategies because of their lack of chiral centers. 8,11 Recently, we described albidopyrone, a new a-pyrone metabolite substituted in position 6 with a phenyl group, produced by a marinederived Streptomyces strain. Albidopyrone showed an inhibitory activity against protein-tyrosine phosphatase B1, similar to gombapyrones.…”

Section: S Helaly Et Almentioning

confidence: 99%

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

et al. 2009

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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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Section: S Helaly Et Almentioning

confidence: 99%

Section: S Helaly Et Almentioning

confidence: 99%

Section: S Helaly Et Almentioning

confidence: 99%

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

et al. 2009

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“…3656-A1, a derivative of a class of fungal secondary metabolites known as 2-pyrones (Tomikawa et al 2000). 2-pyrones have been previously reported to have a broad range of biological activities (Hilgeroth 2002; Marrison et al 2002; McGlacken and Fairlamb 2005). Recently, rasfonin was shown to induce the death of ras-mutated pancreatic tumour (Panc-1) cells (Xiao et al 2014).…”

Section: Introductionmentioning

confidence: 99%

Fungal secondary metabolites rasfonin induces autophagy, apoptosis and necroptosis in renal cancer cell line

Sun

Che²,

Jiang

2016

Mycology

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Rasfonin (A304) is a fungal natural product isolated from the fermentation substrate of Talaromyces sp. 3656-A1, which was named according to its activity against the small G-protein Ras. In a former study, we demonstrated that it induced autophagy and apoptosis; however, whether rasfonin activated necroptosis remained unknown. Moreover, the interplay among different cell death processes induced by rasfonin was unexplored. In the present study, we revealed that, in addition of promoting autophagy and caspase-dependent apoptosis, rasfonin also activated necroptosis. Nectrostatin-1 (Nec-1), an inhibitor of necroptosis, affected rasfonin-induced autophagy in a time-dependent manner concurring with an increased caspase-dependent apoptosis. The aforementioned results were confirmed by knockdown of receptor-interacting protein 1 (RIP1), a crucial necrostatin-1-targeted adaptor kinase mediating cell death and survival. Taken together, the data presented indicate that rasfonin activates various cell death pathways, and RIP1 plays a critical role in rasfonin-induced autophagy and apoptosis.

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“…3656-A1, is a derivative of a class of fungal secondary metabolites known as 2-pyrones (Tomikawa et al 2000). 2-Pyrones have been previously reported to have a broad range of biological activities including antimicrobial, antiviral, antitumor and anti-inflammatory effects (Hilgeroth 2002; Marrison et al 2002; McGlacken & Fairlamb 2005). Coumarins, important sort of 2-pyrones derivative, target a number of pathways in cancer such as kinase inhibition, cell cycle arrest, angiogenesis inhibition and antimitotic activity (Thakur et al 2015).…”

Section: Introductionmentioning

confidence: 99%

Proteasome inhibition attenuates rasfonin-induced autophagy concurring with the upregulation of caspase-dependent apoptosis

Yan

Che²,

Jiang

2016

Mycology

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Two major protein quality control mechanisms exist in eukaryotic cells, the ubiquitin-proteasome system (UPS) and the autophagy–lysosome system. Generally, the inhibition of UPS is believed to enhance autophagic pathway; nevertheless, the crosstalk between these two degradation systems may be much more complicated. Rasfonin, a 2-pyrone derivative of fungal secondary metabolites, is demonstrated to have the antitumor effect and can function as an autophagy inducer. Here, we reported that rasfonin activated multiple cell death pathways, including caspase-dependent apoptosis. Using electroscopy and microscopy, we observed rasfonin increased the formation of autophagosome. In immunoblotting assay, rasfonin enhanced autophagic flux concomitant with the upregulation of ubiquitination. MG132, an inhibitor of proteasome, attenuated rasfonin-dependent autophagy, whereas its presentation stimulated rasfonin-induced cleavage of poly (ADP-ribose) polymerase, a marker of caspase-dependent apoptosis. Together, we demonstrated that rasfonin induced the activation of both UPS and autophagic pathway, and the inhibition of UPS attenuated rasfonin-induced autophagy and enhanced the cytotoxicity of rasonin by upregulation of caspase-dependent apoptosis.

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2-Pyrone natural products and mimetics: isolation, characterisation and biological activity

Cited by 320 publications

References 196 publications

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

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

Fungal secondary metabolites rasfonin induces autophagy, apoptosis and necroptosis in renal cancer cell line

Proteasome inhibition attenuates rasfonin-induced autophagy concurring with the upregulation of caspase-dependent apoptosis

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