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

Nguyen Tuan Hiep†, Yun-hyeok Choi†, Nahyun Kim†, Seong Su Hong†‡, Seung-Beom Hong§, Bang Yeon Hwang, Hak-Ju Lee, Sung-Joon Lee†, Dae Sik Jang*#, and Dongho Lee*†

^† School of Life Sciences and Biotechnology, Korea University, Seoul 136-713, Republic of Korea

^‡ Natural Products Research Institute, Gyeonggi Institute of Science & Technology Promotion, Suwon 443-270, Republic of Korea

^§ Korean Agricultural Culture Collection, National Academy of Agricultural Science, Suwon 441-707, Korea

College of Pharmacy, Chungbuk National University, Cheongju 361-763, Republic of Korea

Korea Forest Research Institute, Seoul 130-712, Korea

^# College of Pharmacy, Kyung Hee University, Seoul 130-701, Korea

J. Nat. Prod., Article ASAP

DOI: 10.1021/np200955z

Publication Date (Web): March 16, 2012

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.