Synthesis and evaluation of novel peptidomimetics bearing p -aminobenzoic acid moiety as potential antidiabetic agents.

Aim: Search for a new class of potential antidiabetic agents. Methodology: A series of novel peptidomimetics bearing the p -aminobenzoic acid moiety ( TM3 - TM6 ) were designed and synthesized. For all synthetic target molecules, the peroxisome proliferator response element (PPRE) activated activities have been evaluated and the toxicity were computed. Results & discussion: 46 new p -aminobenzoic acid derivatives have been characterized by ¹ H NMR, ¹³ C NMR and high-resolution mass spectrometry (HRMS). The results of in vitro PPRE-activated activity, molecular docking study and toxicity prediction revealed that these compounds had potential antidiabetic activities and low toxicity. In particular compound 3b had up to 87% PPRE-activated activity compared with pioglitazone. This discovery may provide new insights for finding novel PPRE lead compound.