2,5-Disubstituted thiadiazoles as potent ß-glucuronidase inhibitors; Synthesis, in vitro and in silico studies.
Bioorg Chem
; 91: 103126, 2019 10.
Article
in En
| MEDLINE
| ID: mdl-31349116
ABSTRACT
Twenty-five thiadiazole derivatives 1-25 were synthesized from methyl 4-methoxybenzoate via hydrazide and thio-hydrazide intermediates, and evaluated for their potential against ß-glucuronidase enzyme. Most of the compounds including 1 (IC50â¯=â¯26.05⯱â¯0.60⯵M), 2 (IC50â¯=â¯42.53⯱â¯0.80⯵M), 4 (IC50â¯=â¯38.74⯱â¯0.70⯵M), 5 (IC50â¯=â¯9.30⯱â¯0.29⯵M), 6 (IC50â¯=â¯6.74⯱â¯0.26⯵M), 7 (IC50â¯=â¯18.40⯱â¯0.66⯵M), and 15 (IC50â¯=â¯18.10⯱â¯0.53⯵M) exhibited superior activity potential than the standard d-saccharic acid-1,4-lactone (IC50â¯=â¯48.4⯱â¯1.25⯵M). Molecular docking studies were conducted to correlate the in vitro results and to identify possible mode of interaction with enzyme active site.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thiadiazoles
/
Enzyme Inhibitors
/
Glucuronidase
Limits:
Humans
Language:
En
Journal:
Bioorg Chem
Year:
2019
Document type:
Article