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New Austalides from the Sponge‐Associated Fungus Aspergillus sp.
Author(s) -
Zhou Yaming,
Mándi Attila,
Debbab Abdessamad,
Wray Victor,
Schulz Barbara,
Müller Werner E. G.,
Lin WenHan,
Proksch Peter,
Kurtán Tibor,
Aly Amal H.
Publication year - 2011
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201100670
Subject(s) - chemistry , phthalide , circular dichroism , absolute configuration , stereochemistry , sponge , chromophore , time dependent density functional theory , mtt assay , cytotoxicity , polyketide , fungus , density functional theory , computational chemistry , organic chemistry , enzyme , biochemistry , botany , biosynthesis , cell , in vitro , biology
Chromatographic separation of a crude extract obtained from the fungus Aspergillus sp., isolated from the Mediterranean sponge Tethya aurantium , yielded five new meroterpenoid metabolites, austalides M–Q ( 1 – 5 ), together with nine known compounds ( 6 – 13 ). The structures of the new compounds were unambiguously elucidated on the basis of extensive 1D and 2D NMR methods and by mass spectral analysis. Furthermore, the absolute configurations of 1 and 4 were determined by time‐dependent density functional theory electronic circular dichroism (TDDFT ECD) calculations, allowing the assignment of the absolute configuration of analogous compounds 2 , 3 , and 5 . The calculations revealed that the conformation of the benzene‐fused phthalide chromophore, which is sensitive to even minor changes in its proximity, is decisive for the ECD parameters, rendering a simple ECD comparison of related homochiral austalides difficult. All compounds were evaluated for their cytotoxic activity against murine cancer cell line L5178Y by using the MTT method. Compounds 8 and 11 exhibited moderate to pronounced cytotoxicity, with IC 50 values of 39.4 and 0.2 μ M , respectively, whereas the remaining investigated compounds showed either weak or no activity in this assay.