Polyhydroxylated Macrolides from Seimatosporium discosioides and Their Effects on the Activation of Peroxisome Proliferator-Activated Receptor Gamma

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 configurati...

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Published in:Journal of natural products (Washington, D.C.) D.C.), 2012-04, Vol.75 (4), p.784-788
Main Authors: Hiep, Nguyen Tuan, Choi, Yun-hyeok, Kim, Nahyun, Hong, Seong Su, Hong, Seung-Beom, Hwang, Bang Yeon, Lee, Hak-Ju, Lee, Sung-Joon, Jang, Dae Sik, Lee, Dongho
Format: Article
Language:English
Subjects:
Glucose-6-Phosphatase - genetics
Hep G2 Cells
Hepatocytes - metabolism
Humans
Macrolides - chemistry
Macrolides - isolation & purification
Macrolides - pharmacology
Molecular Structure
Nuclear Magnetic Resonance, Biomolecular
Phosphoenolpyruvate Carboxykinase (ATP) - genetics
PPAR gamma - drug effects
PPAR gamma - genetics
RNA - isolation & purification
Stereoisomerism
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Summary: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 EC50 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.
ISSN:0163-3864
1520-6025
DOI:10.1021/np200955z