Bioactive metabolites from the endophytic fungus Stemphylium globuliferum isolated from Mentha pulegium.
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 five new secondary metabolites, alterporriol G (4) and its atropisomer alterporriol H (5), altersolanol K (11), altersolanol L (12), stemphypyrone (13), and the known compounds 6-O-methylalaternin (1), macrosporin (2), altersolanol A (3), alterporriol E (6), alterporriol D (7), alterporriol A (8), alterporriol B (9), and altersolanol J (10). 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 (4/5) exhibited considerable cytotoxicity against L5178Y cells with an EC(50) value of 2.7 microg/mL, whereas the other congeners showed only modest activity. The compounds were also tested for kinase inhibitory activity in an assay involving 24 different kinases. Compounds 1, 2, 3, and the mixture of 4 and 5 were the most potent inhibitors, displaying EC(50) values between 0.64 and 1.4 microg/mL toward individual kinases.
Debbab
Abdessamad
A
Institut fur Pharmazeutische Biologie and Biotechnologie, Heinrich-Heine-Universitat, Dusseldorf, Germany.
Aly
Amal H
AH
Edrada-Ebel
Ruangelie
R
Wray
Victor
V
Müller
Werner E G
WE
Totzke
Frank
F
Zirrgiebel
Ute
U
Schächtele
Christoph
C
Kubbutat
Michael H G
MH
Lin
Wen Han
WH
Mosaddak
Mahjouba
M
Hakiki
Abdelhak
A
Proksch
Peter
P
Ebel
Rainer
R
D000818:Animals; D000880:Anthraquinones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D001203:Ascomycota / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D031335:Mentha pulegium / Q000382:microbiology*; D051379:Mice; D015394:Molecular Structure; D009018:Morocco; D018547:Plant Stems / Q000382:microbiology; D010946:Plants, Medicinal / Q000382:microbiology*; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D013237:Stereoisomerism
D000880:Anthraquinones; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C064250:alterporriol D