Protein kinase inhibitors from the endophytic fungus stemphylium globuliferum

A. Debbab, R. Ebel, R.A. Edrada-Ebel, V. Wray, M.H.G. Kubbutat, P. Proksch

Research output: Contribution to journalConference Contribution

Abstract

The endophytic fungus Stemphylium globuliferum was isolated from stem tissues of the Moroccan medicinal plant Mentha pulegium. Extracts of the fungus, which was grown on solid rice medium, exhibited considerable cytotoxicity when tested in vitro against L5178Y cells. Chemical investigation yielded eight new secondary metabolites, alterporriol F, alterporriol G and its atropisomer H, alterporriol I and its atropisomer J, altersolanol K, altersolanol L and stemphypyrone, beside eight known compounds. The structures were determined on the basis of one- and two-dimensional NMR spectroscopy and mass spectrometry. Among the alterporriol-type anthranoid dimers, the mixture of alterporriols G and H exhibited considerable cytotoxicity against L5178Y cells with an EC50 value of 2.7 µg/mL, whereas the other congeners showed only modest activity. The compounds were also tested for protein kinase inhibitory activity in an assay involving 24 different kinases. Compounds methylalaternin, macrosporin, altersolanol A and the mixture of alterporriol G and H were the most potent and also selective inhibitors, displaying EC50 values between 0.64 and 1.4 µg/mL toward individual kinases.
LanguageEnglish
Pages884-884
Number of pages0
JournalPlanta Medica
Volume75
Issue number9
DOIs
Publication statusPublished - Jul 2009

Fingerprint

Protein Kinase Inhibitors
Cytotoxicity
Fungi
Mentha pulegium
Phosphotransferases
Anthraquinones
Medicinal Plants
Metabolites
Dimers
Protein Kinases
Nuclear magnetic resonance spectroscopy
Mass spectrometry
Assays
Mass Spectrometry
Magnetic Resonance Spectroscopy
Tissue
altersolanol A
macrosporin
In Vitro Techniques
Oryza

Keywords

  • endophytic fungus
  • stemphylium globuliferum
  • isolated
  • stem tissues
  • moroccan medicinal plant
  • mentha pulegium
  • cytotoxicity

Cite this

Debbab, A. ; Ebel, R. ; Edrada-Ebel, R.A. ; Wray, V. ; Kubbutat, M.H.G. ; Proksch, P. / Protein kinase inhibitors from the endophytic fungus stemphylium globuliferum. In: Planta Medica. 2009 ; Vol. 75, No. 9. pp. 884-884.
@article{d15cff6d61ac4dcb90e5485b05d12a93,
title = "Protein kinase inhibitors from the endophytic fungus stemphylium globuliferum",
abstract = "The endophytic fungus Stemphylium globuliferum was isolated from stem tissues of the Moroccan medicinal plant Mentha pulegium. Extracts of the fungus, which was grown on solid rice medium, exhibited considerable cytotoxicity when tested in vitro against L5178Y cells. Chemical investigation yielded eight new secondary metabolites, alterporriol F, alterporriol G and its atropisomer H, alterporriol I and its atropisomer J, altersolanol K, altersolanol L and stemphypyrone, beside eight known compounds. The structures were determined on the basis of one- and two-dimensional NMR spectroscopy and mass spectrometry. Among the alterporriol-type anthranoid dimers, the mixture of alterporriols G and H exhibited considerable cytotoxicity against L5178Y cells with an EC50 value of 2.7 µg/mL, whereas the other congeners showed only modest activity. The compounds were also tested for protein kinase inhibitory activity in an assay involving 24 different kinases. Compounds methylalaternin, macrosporin, altersolanol A and the mixture of alterporriol G and H were the most potent and also selective inhibitors, displaying EC50 values between 0.64 and 1.4 µg/mL toward individual kinases.",
keywords = "endophytic fungus, stemphylium globuliferum, isolated, stem tissues, moroccan medicinal plant, mentha pulegium, cytotoxicity",
author = "A. Debbab and R. Ebel and R.A. Edrada-Ebel and V. Wray and M.H.G. Kubbutat and P. Proksch",
year = "2009",
month = "7",
doi = "10.1055/s-0029-1234259",
language = "English",
volume = "75",
pages = "884--884",
journal = "Planta Medica",
issn = "0032-0943",
number = "9",

}

Protein kinase inhibitors from the endophytic fungus stemphylium globuliferum. / Debbab, A.; Ebel, R.; Edrada-Ebel, R.A.; Wray, V.; Kubbutat, M.H.G.; Proksch, P.

In: Planta Medica, Vol. 75, No. 9, 07.2009, p. 884-884.

Research output: Contribution to journalConference Contribution

TY - JOUR

T1 - Protein kinase inhibitors from the endophytic fungus stemphylium globuliferum

AU - Debbab, A.

AU - Ebel, R.

AU - Edrada-Ebel, R.A.

AU - Wray, V.

AU - Kubbutat, M.H.G.

AU - Proksch, P.

PY - 2009/7

Y1 - 2009/7

N2 - The endophytic fungus Stemphylium globuliferum was isolated from stem tissues of the Moroccan medicinal plant Mentha pulegium. Extracts of the fungus, which was grown on solid rice medium, exhibited considerable cytotoxicity when tested in vitro against L5178Y cells. Chemical investigation yielded eight new secondary metabolites, alterporriol F, alterporriol G and its atropisomer H, alterporriol I and its atropisomer J, altersolanol K, altersolanol L and stemphypyrone, beside eight known compounds. The structures were determined on the basis of one- and two-dimensional NMR spectroscopy and mass spectrometry. Among the alterporriol-type anthranoid dimers, the mixture of alterporriols G and H exhibited considerable cytotoxicity against L5178Y cells with an EC50 value of 2.7 µg/mL, whereas the other congeners showed only modest activity. The compounds were also tested for protein kinase inhibitory activity in an assay involving 24 different kinases. Compounds methylalaternin, macrosporin, altersolanol A and the mixture of alterporriol G and H were the most potent and also selective inhibitors, displaying EC50 values between 0.64 and 1.4 µg/mL toward individual kinases.

AB - The endophytic fungus Stemphylium globuliferum was isolated from stem tissues of the Moroccan medicinal plant Mentha pulegium. Extracts of the fungus, which was grown on solid rice medium, exhibited considerable cytotoxicity when tested in vitro against L5178Y cells. Chemical investigation yielded eight new secondary metabolites, alterporriol F, alterporriol G and its atropisomer H, alterporriol I and its atropisomer J, altersolanol K, altersolanol L and stemphypyrone, beside eight known compounds. The structures were determined on the basis of one- and two-dimensional NMR spectroscopy and mass spectrometry. Among the alterporriol-type anthranoid dimers, the mixture of alterporriols G and H exhibited considerable cytotoxicity against L5178Y cells with an EC50 value of 2.7 µg/mL, whereas the other congeners showed only modest activity. The compounds were also tested for protein kinase inhibitory activity in an assay involving 24 different kinases. Compounds methylalaternin, macrosporin, altersolanol A and the mixture of alterporriol G and H were the most potent and also selective inhibitors, displaying EC50 values between 0.64 and 1.4 µg/mL toward individual kinases.

KW - endophytic fungus

KW - stemphylium globuliferum

KW - isolated

KW - stem tissues

KW - moroccan medicinal plant

KW - mentha pulegium

KW - cytotoxicity

U2 - 10.1055/s-0029-1234259

DO - 10.1055/s-0029-1234259

M3 - Conference Contribution

VL - 75

SP - 884

EP - 884

JO - Planta Medica

T2 - Planta Medica

JF - Planta Medica

SN - 0032-0943

IS - 9

ER -