[5-(Benzyloxy)-1H-indol-1-yl]acetic acid, an aldose reductase inhibitor and PPAR gamma ligand


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Prnova M. S. , Majekova M., Milackova I., Diez-Dacal B., Perez-Sala D., Ceyhan M. S. , ...Daha Fazla

ACTA BIOCHIMICA POLONICA, cilt.62, ss.523-528, 2015 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 62 Konu: 3
  • Basım Tarihi: 2015
  • Doi Numarası: 10.18388/abp.2014_953
  • Dergi Adı: ACTA BIOCHIMICA POLONICA
  • Sayfa Sayıları: ss.523-528

Özet

Based on overlapping structural requirements for both efficient aldose reductase inhibitors and PPAR ligands, [5-(benzyloxy)-1H-indol-1-yl] acetic acid (compound 1) was assessed for inhibition of aldose reductase and ability to interfere with PPAR gamma. Aldose reductase inhibition by 1 was characterized by IC50 in submicromolar and low micromolar range, for rat and human enzyme, respectively. Selectivity in relation to the closely related rat kidney aldehyde reductase was characterized by approx. factor 50. At organ level in isolated rat lenses, compound 1 significantly inhibited accumulation of sorbitol in a concentration-dependent manner. To identify crucial interactions within the enzyme binding site, molecular docking simulations were performed. Based on luciferase reporter assays, compound 1 was found to act as a ligand for PPAR gamma, yet with rather low activity. On balance, compound 1 is suggested as a promising lead-like scaffold for agents with the potential to interfere with multiple targets in diabetes.