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

TOKALI F. S., Demir Y., Demircioglu I. H., TÜRKEŞ C., Kalay E., Sendil K., ...Daha Fazla

DRUG DEVELOPMENT RESEARCH, cilt.83, sa.3, ss.586-604, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 83 Sayı: 3
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1002/ddr.21887
  • Dergi Adı: DRUG DEVELOPMENT RESEARCH
  • Derginin Tarandığı İndeksler: 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
  • Sayfa Sayıları: ss.586-604
  • Anahtar Kelimeler: ADME-Tox, aldose reductase, epalrestat, in silico study, molecular docking, quinazolinones, CARBONIC-ANHYDRASE, MOLECULAR DOCKING, ACETYLCHOLINESTERASE, DESIGN, VITRO, ANTICONVULSANT, ANTITUMOR, PROTEIN, BUTYRYLCHOLINESTERASE, QUINAZOLINONES
  • Anadolu Üniversitesi Adresli: Evet

Özet

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, H-1-NMR, C-13-NMR, and HRMS. All the novel quinazolinones (1-21) demonstrated nanomolar levels of inhibitory activity against ALR2 (K(I)s 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 Schrodinger 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.