TY - JOUR
T1 - Bioactive metabolites from Chaetomium aureum
T2 - Structure elucidation and inhibition of the Hsp90 machine chaperoning activity
AU - Kabbaj, Fatima Zahra
AU - Lu, Su
AU - Faouzi, My El Abbés
AU - Meddah, Bouchra
AU - Proksch, Peter
AU - Cherrah, Yahya
AU - Altenbach, Hans Josef
AU - Aly, Amal H.
AU - Chadli, Ahmed
AU - Debbab, Abdessamad
N1 - Funding Information:
This study was supported by grants of the BMBF (F.K.Z. 01DH12030) awarded to A. Debbab. This work was supported by NIH grant R01 grant GM102443-01 to A. Chadli. We would like to thank Prof. F.Z. ALAOUI Department of Botany, Faculty of Sciences, Mohamed V University, and Prof. Dr. M. IBN TATOU, Scientific Institute of Rabat, Morocco, for the plant identification.
Publisher Copyright:
© 2014 Elsevier Ltd. All rights reserved.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - Chemical investigation of the EtOAc extract of the fungus Chaetomium aureum, an endophyte of the Moroccan medicinal plant Thymelaea lythroides, afforded one new resorcinol derivative named chaetorcinol, together with five known metabolites. The structures of the isolated compounds were determined on the basis of one- and two-dimensional NMR spectroscopy and high-resolution mass spectrometry as well as by comparison with the literature. All compounds were tested for their activity towards the Hsp90 chaperoning machine in vitro using the progesterone receptor (PR) and rabbit reticulocyte lysate (RRL). Among the isolated compounds, only sclerotiorin efficiently inhibited the Hsp90 machine chaperoning activity. However, sclerotiorin showed no cytotoxic effect on breast cancer Hs578T, MDA-MB-231 and prostate cancer LNCaP cell lines. Interestingly, deacetylation of sclerotiorin increased its cytotoxicity toward the tested cell lines over a period of 48 h.
AB - Chemical investigation of the EtOAc extract of the fungus Chaetomium aureum, an endophyte of the Moroccan medicinal plant Thymelaea lythroides, afforded one new resorcinol derivative named chaetorcinol, together with five known metabolites. The structures of the isolated compounds were determined on the basis of one- and two-dimensional NMR spectroscopy and high-resolution mass spectrometry as well as by comparison with the literature. All compounds were tested for their activity towards the Hsp90 chaperoning machine in vitro using the progesterone receptor (PR) and rabbit reticulocyte lysate (RRL). Among the isolated compounds, only sclerotiorin efficiently inhibited the Hsp90 machine chaperoning activity. However, sclerotiorin showed no cytotoxic effect on breast cancer Hs578T, MDA-MB-231 and prostate cancer LNCaP cell lines. Interestingly, deacetylation of sclerotiorin increased its cytotoxicity toward the tested cell lines over a period of 48 h.
KW - Bioactive metabolites
KW - Chaetomium aureum
KW - Cytotoxicity
KW - Structure elucidation Hsp90
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U2 - 10.1016/j.bmc.2014.11.021
DO - 10.1016/j.bmc.2014.11.021
M3 - Article
C2 - 25482429
AN - SCOPUS:84918817363
SN - 0968-0896
VL - 23
SP - 126
EP - 131
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 1
ER -