title: Polyhydroxylated macrolides from Seimatosporium discosioides and their effects on the activation of peroxisome proliferator-activated receptor gamma.
abstract: Two new polyhydroxylated macrolides, seimatopolides A (1) and B (2), were isolated from an EtOAc extract of Seimatosporium discosioides culture medium. The structures of the new compounds were established on the basis of spectroscopic analysis, including 1D and 2D NMR, and their absolute configurations were determined using the modified Mosher's method. Seimatopolides A (1) and B (2) activated peroxisome proliferator-activated receptor (PPAR)-γ with EC(50) values of 1.15 and 11.05 μM, respectively. The expression of PPAR-γ target genes in HepG2 hepatocytes was significantly altered; in particular, expression of the gluconeogenic genes glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) was reduced upon stimulation with 1, supporting the proposal that compound 1 is both a PPAR-γ agonist and a possible therapeutic candidate for treatment of diabetes.
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Seoul 136-713, Republic of Korea.
authors.forename: Nguyen Tuan
authors.initials: NT
authors.lastname: Hiep
authors.forename: Yun-hyeok
authors.initials: YH
authors.lastname: Choi
authors.forename: Nahyun
authors.initials: N
authors.lastname: Kim
authors.forename: Seong Su
authors.initials: SS
authors.lastname: Hong
authors.forename: Seung-Beom
authors.initials: SB
authors.lastname: Hong
authors.forename: Bang Yeon
authors.initials: BY
authors.lastname: Hwang
authors.forename: Hak-Ju
authors.initials: HJ
authors.lastname: Lee
authors.forename: Sung-Joon
authors.initials: SJ
authors.lastname: Lee
authors.forename: Dae Sik
authors.initials: DS
authors.lastname: Jang
authors.forename: Dongho
authors.initials: D
authors.lastname: Lee
mesh_terms: D005952:Glucose-6-Phosphatase / Q000235:genetics; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D018942:Macrolides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D047495:PPAR gamma / Q000187:drug effects* / Q000235:genetics; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000235:genetics; D012313:RNA / Q000302:isolation & purification; D013237:Stereoisomerism
chemical_list: D018942:Macrolides; D047495:PPAR gamma; C573610:seimatopolide A; C573611:seimatopolide B; D012313:RNA; D005952:Glucose-6-Phosphatase; D019764:Phosphoenolpyruvate Carboxykinase (ATP)