Premium
Synthesis and Biological Evaluation of 2′‐Oxo‐2,3‐dihydro‐3′ H ‐ spiro[chromene‐4,5′‐[1,3]oxazolidin]‐3′yl]acetic Acid Derivatives as Aldose Reductase Inhibitors
Author(s) -
Rapposelli Simona,
Da Settimo Federico,
Digiacomo Maria,
La Motta Concettina,
Lapucci Annalina,
Sartini Stefania,
Vanni Michael
Publication year - 2011
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201000302
Subject(s) - aldose reductase , aldehyde reductase , sorbinil , chemistry , sorbitol , enzyme , stereochemistry , reductase , polyol pathway , chemical synthesis , acetic acid , aldose reductase inhibitor , enzyme inhibitor , selectivity , aldehyde , biochemistry , catalysis , in vitro
Aldose reductase (ARL2) is the first enzyme in the polyol pathway which catalyzes the NADPH‐dependent reduction of glucose to sorbitol. Its involvement on diabetic complications makes this enzyme a challenge therapeutic target widely investigated to limit and/or prevent them. On this basis, a limited series of 4‐spiro‐oxazolidinone‐benzopyran derivatives ( 1–7 ) were synthesized to evaluate them as potential ARL2 inhibitors. The activity was determined spectrophotometrically by monitoring the oxidation of NADPH catalyzed by ALR2. Within the series of compounds, the 4‐methoxy derivative 1b showed to be the most active compound, exhibiting inhibitory levels in the submicromolar range. In addition, the activity against the aldehyde reductase isoform (ARL1) was also evaluated. Unlike sorbinil (reference drug) that lack of selectivity towards the two enzyme all the tested compounds resulted to be devoid of ARL1 inhibitory activity (IC 50 > 10 µM), thus proving to be selective.