Metabolite Profile of Cucurbitane-Type Triterpenoids of Bitter Melon (Fruit of ) and Their Inhibitory Activity against Protein Tyrosine Phosphatases Relevant to Insulin Resistance.

Qualitative analysis of cucurbitane-type triterpenoids of bitter melon (fruit of L.) using ultraperformance liquid chromatography quadrupole time-of-flight mass spectrometry revealed 27 promising cucurbitane-type triterpenoids, and LC/MS-guided chemical analysis of fruit extract led to the isolation and structural characterization of 22 cucurbitane-type triterpenoids (), including 8 new cucurbitane-type triterpenoidal saponins, yeojoosides A-H (). The structures of the new compounds () were elucidated by spectroscopic methods, including 1D and 2D NMR and high-resolution electrospray ionization mass spectrometry. Their absolute configurations were assigned by quantum chemical electronic circular dichroism calculations, chemical reactions, and DP4+ analysis using gauge-including atomic orbital NMR chemical shift calculations. All isolated compounds () were examined for inhibitory activity against protein tyrosine phosphatases relevant to insulin resistance. Nine compounds (, , , , , , , , and ) showed selective inhibitory effects of over 70% against PTPN2. The present results suggested that these compounds would be potential antidiabetic agents.