ABSTRACT
Seven previously undescribed trichothecenes, named trichothecrotocins M-S (1-7), along with five known compounds, were isolated from rice cultures of the potato-associated fungus Trichothecium crotocinigenum. Their structures and absolute configurations were determined through spectroscopic methods, single-crystal X-ray diffraction, and quantum chemistry calculations on ECD. Compound 1 possesses a rare 6,11-epoxy moiety in the trichothecene family. Compound 6 exhibited strong cytotoxic activity against MCF-7 cancer cell lines with an IC50 value of 2.34 ± 0.45 µM. It promoted apoptosis induction in MCF-7 cells. Moreover, cell cycle analysis showed cell cycle arrest caused by compound 6 at the G2/M phase which resulted to cell proliferation inhibition and pro-apoptotic activity. Further quantitative real-time PCR (qRT-PCR) analysis confirmed that the G2/M arrest was accompanied by upregulation of p21 and down regulation of cyclins B1 in 6-treated MCF-7 cells.
Subject(s)
Antineoplastic Agents/pharmacology , Hypocreales/chemistry , Solanum tuberosum/chemistry , Trichothecenes/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/metabolism , Apoptosis/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Hypocreales/metabolism , MCF-7 Cells , Molecular Docking Simulation , Molecular Structure , Solanum tuberosum/metabolism , Structure-Activity Relationship , Trichothecenes/chemistry , Trichothecenes/metabolismABSTRACT
Four ergosterol derivatives, named tricholosterols A-D (1-4), have been isolated from the fruiting bodies of Tricholoma terreum. Their chemical structures have been determined using a combination of spectroscopic analysis as well as computational methods. Compound 1 possesses a rare D-ring opening ergosterol skeleton, while compounds 2-4 are rare degraded ergosterols. Compounds 1 and 4 exhibited moderate inhibitory activity against NO production with IC50 values of 27.6 and 31.8 µM, respectively. This is the first report of steroids from T. terreum.