Synthesis of indole-substituted thiosemicarbazones as an aldose reductase inhibitor: an in vitro, selectivity and in silico study.
Future Med Chem
; 13(14): 1185-1201, 2021 07.
Article
in En
| MEDLINE
| ID: mdl-34148377
ABSTRACT
Aim:
Indole is an important component of many drug molecules, and its conjugation with thiosemicarbazone moiety would be advantageous in finding lead compounds for the development of diabetic complications.Methodology:
We have designed, synthesized and evaluated a series of 17 indole-thiosemicarbazones (3a-q) as aldose reductase (ALR2) and aldehyde reductase (ALR1) inhibitors.Results:
After in vitro evaluation, all indole-thiosemicarbazones showed significant inhibition against both enzyme ALR1 and ALR2 with IC50 in range of 0.42-20.7 and 1.02-19.1 µM, respectively. The docking study was also carried out to consider the putative binding of molecules with the target enzymes.Conclusion:
Compound 3f was found to be most active and selective for ALR2. The indole-thiosemicarbazones series described here has selective hits for diabetes-mellitus-associated complications.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thiosemicarbazones
/
Aldehyde Reductase
/
Enzyme Inhibitors
/
Indoles
Limits:
Humans
Language:
En
Journal:
Future Med Chem
Year:
2021
Document type:
Article
Affiliation country: