Synthesis, biological evaluation, and in silico study of novel library sulfonates containing quinazolin-4(3H)-one derivatives as potential aldose reductase inhibitors

Tokalı F. S., Demir Y., Demircioğlu İ. H., TÜRKEŞ C., Kalay E., Şendil K., ...More

Drug Development Research, vol.83, no.3, pp.586-604, 2022 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 83 Issue: 3
  • Publication Date: 2022
  • Doi Number: 10.1002/ddr.21887
  • Journal Name: Drug Development Research
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.586-604
  • Keywords: ADME-Tox, aldose reductase, epalrestat, in silico study, molecular docking, quinazolinones
  • Bilecik Şeyh Edebali University Affiliated: No

Abstract

© 2021 Wiley Periodicals, LLC.A series of novel sulfonates containing quinazolin-4(3H)-one ring derivatives was designed to inhibit aldose reductase (ALR2, EC 1.1.1.21). Novel quinazolinone derivatives (1–21) were synthesized from the reaction of sulfonated aldehydes with 3-amino-2-alkylquinazolin-4(3H)-ones in glacial acetic acid with good yields (85%–94%). The structures of the novel molecules were characterized using IR, 1H-NMR, 13C-NMR, and HRMS. All the novel quinazolinones (1–21) demonstrated nanomolar levels of inhibitory activity against ALR2 (KIs are in the range of 101.50–2066.00 nM). Besides, 4-[(2-isopropyl-4-oxoquinazolin-3[4H]-ylimino)methyl]phenyl benzenesulfonate (15) showed higher inhibitor activity inhibited ALR2 up to 7.7-fold compared to epalrestat, a standard inhibitor. Binding interactions between ALR2 and quinazolinones have been investigated using Schrödinger Small-Molecule Drug Discovery Suite 2021–1, reported possible inhibitor-ALR2 interactions. Both in vitro and in silico study results suggest that these quinazolin-4(3H)-one ring derivatives (1–21) require further molecular modification to improve their drug nominee potency as an ALR2 inhibitor.