Discovery of Isoquinolinoquinazolinones as a Novel Class of Potent PPAR gamma Antagonists with Anti-adipogenic Effects

作者：Jin Yifeng; Han Younho; Khadka Daulat Bikram; Zhao Chao; Lee Kwang Youl^*; Cho Won Jea^*

来源：Scientific Reports, 2016, 6(1): 34661.

DOI：10.1038/srep34661

Conformational change in helix 12 can alter ligand-induced PPAR gamma activity; based on this reason, isoquinolinoquinazolinones, structural homologs of berberine, were designed and synthesized as PPAR gamma antagonists. Computational docking and mutational study indicated that isoquinolinoquinazolinones form hydrogen bonds with the Cys285 and Arg288 residues of PPAR gamma. Furthermore, SPR results demonstrated strong binding affinity of isoquinolinoquinazolinones towards PPAR gamma. Additionally, biological assays showed that this new series of PPAR gamma antagonists more strongly inhibit adipocyte differentiation and PPAR gamma 2-induced transcriptional activity than GW9662.

• 出版日期2016-10-3