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

Autor: Demir Y; Department of Pharmacy Services, Nihat Delibalta Göle Vocational High School, Ardahan University, 75700, Ardahan, Turkey. yelizdemir@ardahan.edu.tr., Tokalı FS; Department of Material and Material Processing Technologies, Kars Vocational School, Kafkas University, 36100, Kars, Turkey., Kalay E; Department of Material and Material Processing Technologies, Kars Vocational School, Kafkas University, 36100, Kars, Turkey. ekalay@kafkas.edu.tr., Türkeş C; Department of Biochemistry, Faculty of Pharmacy, Erzincan Binali Yıldırım University, 24002, Erzincan, Turkey., Tokalı P; Department of Veterinary Physiology, Faculty of Veterinary Medicine, Kafkas University, 36100, Kars, Turkey., Aslan ON; East Anatolian High Technology Application and Research Center, Atatürk University, 25240, Erzurum, Turkey., Şendil K; Department of Chemistry, Faculty of Arts and Science, Kafkas University, 36100, Kars, Turkey., Beydemir Ş; Department of Biochemistry, Faculty of Pharmacy, Anadolu University, 26470, Eskisehir, Turkey.; The Rectorate of Bilecik Şeyh Edebali University, 11230, Bilecik, Turkey.
Jazyk: angličtina
Zdroj: Molecular diversity [Mol Divers] 2023 Aug; Vol. 27 (4), pp. 1713-1733. Date of Electronic Publication: 2022 Sep 14.
DOI: 10.1007/s11030-022-10526-1
Abstrakt: 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 50 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 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.
(© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
Databáze: MEDLINE
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