In vitro inhibition of α-Synuclein aggregation and disaggregation of preformed fibers by polyphenol hybrids with 2-conjugated benzothiazole.
Bioorg Med Chem Lett
; 105: 129752, 2024 Jun 01.
Article
in En
| MEDLINE
| ID: mdl-38631541
ABSTRACT
The misfolding and aggregation of α-Syn play a pivotal role in connecting diverse pathological pathways in Parkinson's disease (PD). Preserving α-Syn proteostasis and functionality by inhibiting its aggregation or disaggregating existing aggregates using suitable inhibitors represents a promising strategy for PD prevention and treatment. In this study, a series of benzothiazole-polyphenol hybrids was designed and synthesized. Three identified compounds exhibited notable inhibitory activities against α-Syn aggregation in vitro, with IC50 values in the low micromolar range. These inhibitors demonstrated sustained inhibitory effects throughout the entire aggregation process, stabilizing α-Syn proteostasis conformation. Moreover, the compounds effectively disintegrated preformed α-Syn oligomers and fibers, potentially by binding to specific domains within the fibers, inducing fibril instability, collapse, and ultimately resulting in smaller-sized aggregates and monomers. These findings offer valuable insights into the therapeutic potential of polyphenol hybrids with 2-conjugated benzothiazole targeting α-Syn aggregation in the treatment of PD.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Benzothiazoles
/
Alpha-Synuclein
/
Polyphenols
/
Protein Aggregates
Limits:
Humans
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
Reino Unido