Deferasirox Derivatives as Inhibitors of Kallikrein-Related Peptidases Associated to Neurodegenerative Diseases.

ABSTRACT: Kallikrein-related peptidases are a family of serine proteases whose loss of activity regulation has been particularly linked to neurodegenerative diseases. Moreover, iron overload is also a key process in some of these leading pathological conditions, particularly Alzheimer's disease. It is identified for the first time Deferasirox, a well-known FDA-approved iron chelator (DFX) as an initial hit for kallikrein's (KLK) inhibition and proposed here the design and synthesis of a small library of molecules using DFX as chemical scaffold. Resulting subseries of compounds are evaluated against lead central nervous system KLK's, namely, KLK1, KLK6, and KLK8 using targeted pharmacomodulations on DFX. Beyond DFX, several reversible micromolar inhibitors of these KLKs have been identified as hits a

SUBMITTER: Boumali R 

PROVIDER: S-EPMC12221113 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature