Oleanolic Acid Amide Derivatives as 20s Proteasome Stimulators.

ABSTRACT: Oleanolic acid (OA), a pentacyclic triterpenoid natural product, is previously identified as a proteasome stimulator using purified proteasome. Structure-activity relationship studies are carried out on OA at the C₂₈ and C₃ positions to determine if modifications at these positions can change proteasome stimulation activity. Ten amide derivatives are synthesized and tested in cells. These findings indicate that replacing the carboxylic acid with an amide at position C₂₈ does not diminish the stimulating effect, with certain functional groups making stimulation more potent. Amides with increased steric hinderance stimulate the proteasome the best, particularly amides with ortho substituted benzyl or isopropyl moieties. OA is further derivatized at the C

SUBMITTER: Osman JM 

PROVIDER: S-EPMC12687569 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature