Peroxisome proliferator-activated receptor- (PPAR) is a nuclear transcription factor which is involved
in many diseases, such as diabetes, inflammation, dyslipidemia, hypertension, and cancer. Recently, there
are many reports showing that PPAR agonists have preclinical and clinical anticancer activity, with
relatively few reports on anticancer effects of PPAR antagonists. From our compound library, a novel
3-thiazolinone-modified benzoic acid derivative HL005 is found as PPAR selective ligand through SPR
analysis (KD = 0.21M), yeast two-hybrid results suggest that HL005 antagonize the potent PPARagonist
rosiglitazone-induced recruitment of the coactivator for PPAR (IC50 = 7.97M). Different from the most
reported PPAR antagonist, HL005 can inhibit the proliferation of MCF-7 cell line in a concentrationdependent
manner and induce cell cycle arrest at G2/M phase, other than interference with cell adhesion.
In order to study the binding mode of this compound, three derivatives are synthesized to get more detail
about the structure–activity relationship, molecular docking and the NMR spectra indicate that similar
to most PPAR ligand, the carboxylic acid group is an important moiety for HL005 and contributes strong
interaction with PPAR.