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 (IC50 > 10 µM), thus proving to be selective.

Synthesis and Biological Evaluation of 2'-Oxo-2,3-dihydro-3'H-spiro[chromene-4,5'-[1,3]oxazolidin]3'il]acetic Acid Derivatives as Aldose reductase Inhibitors

RAPPOSELLI, SIMONA
;
DA SETTIMO PASSETTI, FEDERICO;DIGIACOMO, MARIA;LA MOTTA, CONCETTINA;LAPUCCI, ANNALINA;SARTINI, STEFANIA;
2011

Abstract

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 (IC50 > 10 µM), thus proving to be selective.
Rapposelli, Simona; DA SETTIMO PASSETTI, Federico; Digiacomo, Maria; LA MOTTA, Concettina; Lapucci, Annalina; Sartini, Stefania; Vanni, M.
File in questo prodotto:
File Dimensione Formato  
Rapposelli et al.2011.pdf

solo utenti autorizzati

Tipologia: Versione finale editoriale
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 253.54 kB
Formato Adobe PDF
253.54 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/203670
Citazioni
  • ???jsp.display-item.citation.pmc??? 5
  • Scopus 18
  • ???jsp.display-item.citation.isi??? 17
social impact