Synthesis and biological evaluation of [1,2,4]triazino[4,3-a] benzimidazole acetic acid derivatives as selective aldose reductase inhibitors.
The acetic acid derivatives of [1,2,4]triazino[4,3-a]benzimidazole (TBI) were synthesized and tested in vitro and in vivo as selective aldose reductase (ALR2) inhibitors. Compound PS11 showed highest inhibitory activity (IC(50)) 0.32 microM and was found to be effective in preventing cataract development in severely galactosemic rats when administered as an eyedrop solution. All the compounds investigated were selective for ALR2, since none of them inhibited appreciably aldehyde reductase, sorbitol dehydrogenase, or glutathione reductase.
Sahoo
Prasanta Kumar
PK
Sri Vasavi Institute of Pharmaceutical Sciences, Pedatadepalli, Tadepalligudem, West Godavari District 534101, Andhra Pradesh, India. psahoo.phar@gmail.com
Behera
Pritishova
P
D019342:Acetic Acid / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002386:Cataract / Q000150:complications / Q000517:prevention & control*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D005693:Galactosemias / Q000150:complications; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009281:Naphthalenes / Q000494:pharmacology; D009883:Ophthalmic Solutions / Q000494:pharmacology; D051381:Rats
D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D009883:Ophthalmic Solutions; C040550:tolrestat; D000449:Aldehyde Reductase; D019342:Acetic Acid