Structural Congeners of Izenamides Responsible for Cathepsin D Inhibition: Insights from Synthesis-Derived Elucidation.

ABSTRACT: This study aimed to elucidate the structural congeners of natural izenamides A, B, and C (1-3) responsible for cathepsin D (CTSD) inhibition. Structurally modified izenamides were synthesized and biologically evaluated, and their biologically important core structures were identified. We confirmed that the natural statine (Sta) unit (3S,4S)-γ-amino-β-hydroxy acid is a requisite core structure of izenamides for inhibition of CTSD, which is closely related to the pathophysiological roles in numerous human diseases. Interestingly, the statine-incorporated izenamide C variant (7) and 18-epi-izenamide B variant (8) exhibited more potent CTSD-inhibitory activities than natural izenamides.

SUBMITTER: Kim HS 

PROVIDER: S-EPMC10223608 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature