Structural diversity of new C13-polyketides produced by Chaetomium mollipilium cultivated in the presence of a NAD(+)-dependent histone deacetylase inhibitor.
Cultivation of Chaetomium mollipilium with nicotinamide, a NAD(+)-dependent HDAC inhibitor, stimulated its secondary metabolism, leading to the isolation of structurally diverse new C(13)-polyketides, mollipilin A-E (1-5) as well as two known compounds (6 and 7). Spectroscopic methods, X-ray single crystal diffraction analysis, and VCD elucidated the absolute configurations of structures 1-6, and plausible biosynthetic pathways for 1-7 were proposed based on structural relationships. Mollipilins A (1) and B (2) exhibited moderate growth inhibitory effects on HCT-116 cells.
Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-yama, Aoba-ku, Sendai 980-8578, Japan. tasai@m.tohoku.ac.jp
Teigo
T
Asai
Shuntaro
S
Morita
Naoki
N
Shirata
Tohru
T
Taniguchi
Kenji
K
Monde
Hiroaki
H
Sakurai
Tomoji
T
Ozeki
Yoshiteru
Y
Oshima
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002597:Chaetomium / Q000737:chemistry*; D018360:Crystallography, X-Ray; D056545:Group III Histone Deacetylases / Q000378:metabolism*; D045325:HCT116 Cells; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D009243:NAD / Q000378:metabolism; D009536:Niacinamide / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D061065:Polyketides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D056572:Histone Deacetylase Inhibitors; D061065:Polyketides; C578108:mollipilin A; C578109:mollipilin B; D009243:NAD; D009536:Niacinamide; D056545:Group III Histone Deacetylases