Green asymmetric synthesis of epoxypeptidomimetics and evaluation as human cathepsin K inhibitors.
Bioorg Med Chem
; 28(15): 115597, 2020 08 01.
Article
in En
| MEDLINE
| ID: mdl-32631567
ABSTRACT
Cathepsin K (CatK) is a cysteine protease known for its potent collagenolytic activity, being recognized as an important target to the development of therapies for the treatment of bone disorders. Epoxypeptidomimetics have been reported as potent inhibitors of cathepsins, thus in this work we present a green synthesis of new peptidomimetics by using a one-pot asymmetric epoxidation/Ugi multicomponent reaction. The compounds were evaluated against CatK showing selectivity when compared with cathepsin L, with an inhibition profile in the low micromolar IC50 range. Investigation of the mechanism of action carried out for compounds LSPN428 and LSPN694 suggested a mixed inhibition mode and docking studies allowed a better understanding about interactions of inhibitors with the enzyme.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cysteine Proteinase Inhibitors
/
Epoxy Compounds
/
Cathepsin K
/
Peptidomimetics
Limits:
Humans
Language:
En
Journal:
Bioorg Med Chem
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2020
Document type:
Article
Publication country:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM