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Synthesis and characterization of novel acyl hydrazones derived from vanillin as potential aldose reductase inhibitors    
Yazarlar
Yeliz Demir
Ardahan Üniversitesi, Türkiye
Doç. Dr. Feyzi Sinan TOKALI Doç. Dr. Feyzi Sinan TOKALI
Kafkas Üniversitesi, Türkiye
Doç. Dr. Erbay KALAY Doç. Dr. Erbay KALAY
Kafkas Üniversitesi, Türkiye
Cüneyt Türkeş
Erzincan Binali Yıldırım Üniversitesi, Türkiye
Pelin Tokalı
Türkiye
Osman Nuri Aslan
Atatürk Üniversitesi, Türkiye
Kıvılcım Şendil
Kafkas Üniversitesi, Türkiye
Şükrü Beydemir
Anadolu Üniversitesi, Türkiye
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 IC and K 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 11c 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.
Anahtar Kelimeler
Aldose reductase | Acyl hydrazones | Vanillin | Epalrestat | In silico study | ADME-Tox | Molecular docking
Makale Türü Özgün Makale
Makale Alt Türü SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale
Dergi Adı MOLECULAR DIVERSITY
Dergi ISSN 1381-1991
Dergi Tarandığı Indeksler SCI-Expanded
Dergi Grubu Q2
Makale Dili İngilizce
Basım Tarihi 08-2023
Cilt No 27
Sayı 4
Sayfalar 1713 / 1733
Doi Numarası 10.1007/s11030-022-10526-1
Makale Linki https://link.springer.com/content/pdf/10.1007/s11030-022-10526-1.pdf