Bioactive metabolites from Chaetomium aureum: Structure elucidation and inhibition of the Hsp90 machine chaperoning activity

• Published in: Bioorganic & medicinal chemistry Vol. 23; no. 1; pp. 126 - 131
• Main Authors: Kabbaj, Fatima Zahra, Lu, Su, Faouzi, My El Abbés, Meddah, Bouchra, Proksch, Peter, Cherrah, Yahya, Altenbach, Hans-Josef, Aly, Amal H., Chadli, Ahmed, Debbab, Abdessamad
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.01.2015; Elsevier
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Bioactive metabolites; Biochemistry & Molecular Biology; Breast Neoplasms - drug therapy; Cell Line, Tumor; Chaetomium; Chaetomium - chemistry; Chaetomium aureum; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Cytotoxicity; Female; Hsp90; HSP90 Heat-Shock Proteins - antagonists & inhibitors; HSP90 Heat-Shock Proteins - metabolism; Humans; Life Sciences & Biomedicine; Magnetic Resonance Spectroscopy; Mass Spectrometry; Pharmacology & Pharmacy; Physical Sciences; Rabbits; Resorcinols - chemistry; Resorcinols - pharmacology; Science & Technology; Structure elucidation; Thymelaea; Hsp90; Cytotoxicity; Chaetomium aureum; Structure elucidation; Bioactive metabolites; APOPTOSIS; SCLEROTIORIN; PROTEIN; PENICILLIUM-FREQUENTANS; NATURAL-PRODUCTS; CANCER; ENDOPHYTIC FUNGUS; AZAPHILONES; DERIVATIVES; BINDING
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2014.11.021

[Display omitted] 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 48h.