Design, synthesis and biological evaluation of 1,5-disubstituted α-amino tetrazole derivatives as non-covalent inflammasome-caspase-1 complex inhibitors with potential application against immune and inflammatory disorders.
Eur J Med Chem
; 229: 114002, 2022 Feb 05.
Article
in English
| MEDLINE | ID: covidwho-1517139
ABSTRACT
Compounds targeting the inflammasome-caspase-1 pathway could be of use for the treatment of inflammation and inflammatory diseases. Previous caspase-1 inhibitors were in great majority covalent inhibitors and failed in clinical trials. Using a mixed modelling, computational screening, synthesis and in vitro testing approach, we identified a novel class of non-covalent caspase-1 non cytotoxic inhibitors which are able to inhibit IL-1ß release in activated macrophages in the low µM range, in line with the best activities observed for the known covalent inhibitors. Our compounds could form the basis of further optimization towards potent drugs for the treatment of inflammation and inflammatory disorders including also dysregulated inflammation in Covid 19.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Autoimmune Diseases
/
Tetrazoles
/
Viral Proteins
/
Serpins
/
Anti-Inflammatory Agents, Non-Steroidal
/
Caspase 1
/
Inflammasomes
/
Inflammation
Type of study:
Experimental Studies
/
Prognostic study
Topics:
Traditional medicine
Limits:
Humans
Language:
English
Journal:
Eur J Med Chem
Year:
2022
Document Type:
Article
Similar
MEDLINE
...
LILACS
LIS