Synthesis and characterization of novel acyl hydrazones derived from vanillin as potential aldose reductase inhibitors


Demir Y., TOKALI F. S., Kalay E., TÜRKEŞ C., Tokali P., ASLAN O. N., ...Daha Fazla

MOLECULAR DIVERSITY, cilt.27, sa.4, ss.1713-1733, 2023 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 27 Sayı: 4
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1007/s11030-022-10526-1
  • Dergi Adı: MOLECULAR DIVERSITY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE
  • Sayfa Sayıları: ss.1713-1733
  • Anahtar Kelimeler: Aldose reductase, Acyl hydrazones, Vanillin, Epalrestat, In silico study, ADME-Tox, Molecular docking, CALCIUM-CHANNEL BLOCKERS, CARBONIC-ANHYDRASE I, MONO-MANNICH-BASES, BIOLOGICAL EVALUATION, MOLECULAR DOCKING, OXIDATIVE STRESS, POLYOL PATHWAY, DERIVATIVES, DESIGN, ANTICANCER
  • Anadolu Üniversitesi Adresli: Evet

Özet

In the polyol pathway, aldose reductase (AR) catalyzes the formation of sorbitol from glucose. In order to detoxify some dangerous aldehydes, AR is essential. However, due to the effects of the active polyol pathway, AR overexpression in the hyperglycemic state leads to microvascular and macrovascular diabetic problems. As a result, AR inhibition has been recognized as a potential treatment for issues linked to diabetes and has been studied by numerous researchers worldwide. In the present study, a series of acyl hydrazones were obtained from the reaction of vanillin derivatized with acyl groups and phenolic Mannich bases with hydrazides containing pharmacological groups such as morpholine, piperazine, and tetrahydroisoquinoline. The resulting 21 novel acyl hydrazone compounds were investigated as an inhibitor of the AR enzyme. All the novel acyl hydrazones derived from vanillin demonstrated activity in nanomolar levels as AR inhibitors with IC50 and K-I values in the range of 94.21 +/- 2.33 to 430.00 +/- 2.33 nM and 49.22 +/- 3.64 to 897.20 +/- 43.63 nM, respectively. Compounds lie and 10b against AR enzyme activity were identified as highly potent inhibitors and showed 17.38 and 10.78-fold more effectiveness than standard drug epalrestat. The synthesized molecules' absorption, distribution, metabolism, and excretion (ADME) effects were also assessed. The probable-binding mechanisms of these inhibitors against AR were investigated using molecular-docking simulations.