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, cilt.26, sa.10, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Derleme
  • Cilt numarası: 26 Sayı: 10
  • Basım Tarihi: 2021
  • Doi Numarası: 10.3390/molecules26102867
  • Dergi Adı: MOLECULES
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Communication Abstracts, EMBASE, Food Science & Technology Abstracts, MEDLINE, Metadex, Veterinary Science Database, Directory of Open Access Journals, Civil Engineering Abstracts
  • Anahtar Kelimeler: 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
  • Gazi Üniversitesi Adresli: Evet

Özet

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.