Development of Novel Indole-Based Bifunctional Aldose Reductase Inhibitors/Antioxidants as Promising Drugs for the Treatment of Diabetic Complications


Kovacikova L., Prnova M. S. , Majekova M., Bohac A., KARASU Ç. , Stefek M.

MOLECULES, vol.26, no.10, 2021 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Review
  • Volume: 26 Issue: 10
  • Publication Date: 2021
  • Doi Number: 10.3390/molecules26102867
  • Title of Journal : MOLECULES
  • Keywords: indole, pyridoindole, triazinoindole, aldose reductase, inhibitor, diabetic complications, polyol pathway, antioxidant, PYRIDOINDOLE ANTIOXIDANT STOBADINE, IN-VIVO TREATMENT, LIPID-PEROXIDATION, OXIDATIVE STRESS, DIETARY SUPPLEMENTATION, RENAL NA,K-ATPASE, MATRIX COLLAGEN, CELLULAR-SYSTEM, POLYOL PATHWAY, SERUM-ALBUMIN

Abstract

Aldose reductase (AR, ALR2), the first enzyme of the polyol pathway, is implicated in the pathophysiology of diabetic complications. Aldose reductase inhibitors (ARIs) thus present a promising therapeutic approach to treat a wide array of diabetic complications. Moreover, a therapeutic potential of ARIs in the treatment of chronic inflammation-related pathologies and several genetic metabolic disorders has been recently indicated. Substituted indoles are an interesting group of compounds with a plethora of biological activities. This article reviews a series of indole-based bifunctional aldose reductase inhibitors/antioxidants (ARIs/AOs) developed during recent years. Experimental results obtained in in vitro, ex vivo, and in vivo models of diabetic complications are presented. Structure-activity relationships with respect to carboxymethyl pharmacophore regioisomerization and core scaffold modification are discussed along with the criteria of 'drug-likeness". Novel promising structures of putative multifunctional ARIs/AOs are designed.