Cytotoxic polyketides containing tetramic acid moieties isolated from the fungus Myceliophthora Thermophila: elucidation of the relationship between cytotoxicity and stereoconfiguration.
Five new polyketides that contain tetramic acids, myceliothermophins A-E, were isolated from the thermophilic fungus Myceliophthora thermophila. Two sets of 5-alkyl-5-hydroxyl (or 5-methoxyl)-1H-pyrrol-2(5H)-one diastereomers, myceliothermophins A/B and C/D, were separated as pure compounds by using silica-gel column chromatography and recycling reverse-phase high-performance liquid chromatography (RP-HPLC). The relative configurations of the chiral centers in 5-alkyl-5-hydroxyl (or 5-methoxyl)-1H-pyrrol-2(5H)-one moieties were deduced from NOESY correlations. In the cytotoxic assay, the 5-(2-methylpropyldiene)-1H-pyrrol-2(5H)-one analogue (myceliothermophin E) exhibited inhibition against four cancer cell lines. In addition, the significant inhibitory effect of myceliothermophins A and C and the inactivity of myceliothermophins B and D revealed the importance of the relative configurations of 5-alkyl-5-hydroxyl (or 5-methoxyl)-1H-pyrrol-2(5H)-one moieties on their cytotoxicity potency against cancer cells.
Yang
Yu-Liang
YL
Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan.
Lu
Chun-Ping
CP
Chen
Mao-Yen
MY
Chen
Kuei-Yu
KY
Wu
Yang-Chang
YC
Wu
Shih-Hsiung
SH
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D018942:Macrolides / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D015394:Molecular Structure; D011760:Pyrrolidinones / Q000737:chemistry*; D020037:Sordariales / Q000737:chemistry*; D013237:Stereoisomerism
D018942:Macrolides; D011760:Pyrrolidinones; C009435:tetramic acid