Design, synthesis, and aldose reductase inhibitory effect of some novel carboxylic acid derivatives bearing 2-substituted-6-aryloxo-pyridazinone moiety

Akdağ, Mevlüt; Özçelik, Azime Berna; Demir, Yeliz; Beydemır, Şükrü

doi:10.1016/j.molstruc.2022.132675

Cited by 28 publications

(20 citation statements)

References 52 publications

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“…In this study, the procedures applied in biological studies are provided in the Supporting Information [34–55] …”

Section: Resultsmentioning

confidence: 99%

“…The fractions from gel filtration chromatography were loaded affinity column. The enzyme was eluted by an increasing linear gradient of NaCl (0.25–2.5 mM) [39–42] . Homogenate preparation of SDH was similar with AR.…”

Section: Methodsmentioning

confidence: 99%

“…The enzyme was eluted by an increasing linear gradient of NaCl (0.25-2.5 mM). [39][40][41][42] Homogenate preparation of SDH was similar with AR. As distinct from AR homogenisation, 5 mM Kphosphate buffer was used (pH 7.0).…”

Section: Purification Of Ar and Sdhmentioning

confidence: 98%

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Investigation of The Effect of Acylthiourea Derivatives on Diabetes‐Associated Enzymes

et al. 2022

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One of the most prevalent chronic metabolic disorders, diabetes mellitus, is defined by chronic hyperglycemia and the emergence of microvascular and macrovascular pathology unique to diabetes. Several diabetes problems are primarily caused by persistent hyperglycemia. In this study, aldose reductase (AR) and sorbitol dehydrogenase (SDH) enzymes were purified using chromatographic techniques from sheep kidneys and α-glycosidase purchased commercially. The inhibitory effect of seven acylthiourea compounds on the activity of these enzymes associated with diabetes was investigated. As a result of the studies, the acyl thioureas showed an inhibition effect at the micromolar level on the activity of studied enzymes. The most active compound dimethyl 1-((4-methoxybenzoyl)carbamothioyl)-5,5-diphenylpyrrolidine-2,4-dicarboxylate (2 c) had an excellent selectivity on AR with K i : 0.200 � 0.024 μM and dimethyl 1-((2,4-dichlorobenzoyl)carbamothioyl)-5,5-diphenylpyrrolidine-2,4-dicarboxylate (2 g) on SDH and αglycosidase with K i : 0.114 � 0.01 μM and K i : 055 � 0.01 μM, respectively. The findings suggest that our study will contribute to the development of innovative and/or alternative treatment strategies in the treatment of diabetes in the future since acylthiourea compounds have an effective inhibition capacity on critical enzymes associated with diabetes.

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“…In this study, the procedures applied in biological studies are provided in the Supporting Information [34–55] …”

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Investigation of The Effect of Acylthiourea Derivatives on Diabetes‐Associated Enzymes

et al. 2022

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“…The primary enzyme in the polyol pathway, aldose reductase (AR) that catalyzes the conversion of glucose to sorbitol. 86 It is another toxic substance produced by dysfunctional metabolic processes in diabetes as a result of elevated polyol pathway activity. 87 The last common pathway of difficulties caused by issues caused by hyperglycemia and hyperlipidemia is increased nitrosative and ROS products.…”

Section: Resultsmentioning

confidence: 99%

“…The primary enzyme in the polyol pathway, aldose reductase (AR) that catalyzes the conversion of glucose to sorbitol 86 . It is another toxic substance produced by dysfunctional metabolic processes in diabetes as a result of elevated polyol pathway activity 87 .…”

Section: Resultsmentioning

confidence: 99%

Assessment of hypolipidemic and anti‐inflammatory properties of walnut (Juglans regia) seed coat extract and modulates some metabolic enzymes activity in triton WR‐1339‐induced hyperlipidemia in rat kidney, liver, and heart

Palabıyık

Sulumer

Uguz

et al. 2022

J of Molecular Recognition

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Atherosclerosis and cognitive impairment are both influenced by hyperlipidemia. Due to their high margin of safety and low cost, natural chemicals have recently attracted particular attention in the context of the treatment of disease. Hence, the purpose of this study was to investigate the possible amendatory impact of ethanol extract walnut (Juglans regia) seed coat (E‐WSC) on some metabolic enzymes (glutathione reductase (GR), paraoxonase‐1 (PON1), aldose reductase (AR), sorbitol dehydrogenase (SDH), acetylcholinesterase (AChE), glutathione S‐transferase (GST), and butyrylcholinesterase (BChE)) activity in the liver, kidney, and heart of rats with Triton WR‐1339‐induced hyperlipidemia. Rats were divided into five groups: control group, HL‐Control group (Triton WR‐1339 400 mg/kg, i.p administered group), E‐ WSC + 150 (150 mg/kg,o.d given group), E‐ WSC + 300 (E‐ WSC 300 mg/kg, o.d given group) and HL+ E‐WSC + 300 (Group receiving E‐ WSC 300 mg/kg, o.d 30 min prior to administration of Triton WR‐1339 400 mg/kg, i.p). In HL‐Control, AR, SDH, and BChE enzyme activity was significantly increased in all tissues compared to the control, while the activity of other studied enzymes was significantly decreased. The effects of hyperlipidemia on balance were improved and alterations in the activity of the investigated metabolic enzymes were prevented by E‐WSC. As a result, promising natural compounds that can be used as adjuvant therapy in the treatment of cognitive disorders and hyperlipidemia may be found in E‐WSC powder.

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A new series of hydrazones as small‐molecule aldose reductase inhibitors

Altıntop

Demir

Türkeş

et al. 2023

Archiv der Pharmazie

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In the search for small-molecule aldose reductase (AR) inhibitors, new tetrazolehydrazone hybrids (1-15) were designed. An efficient procedure was employed for the synthesis of compounds 1-15. All hydrazones were subjected to an in vitro assay to assess their AR inhibitory profiles. Compounds 1-15 caused AR inhibition with K i values ranging between 0.177 and 6.322 µM and IC 50 values ranging between 0.210 and 0.676 µM. 2-[(1-(4-Hydroxyphenyl)-1H-tetrazol-5-yl)thio]-N'-(4-fluorobenzylidene) acetohydrazide ( 4) was the most potent inhibitor of AR in this series. Compound 4 markedly inhibited AR (IC 50 = 0.297 µM) in a competitive manner (K i = 0.177 µM) compared to epalrestat (K i = 0.857 µM, IC 50 = 0.267 µM). Based on the in vitro data obtained by applying the MTT test, compound 4 showed no cytotoxic activity toward normal (NIH/3T3) cells at the tested concentrations, indicating its safety as an AR inhibitor. Compound 4 exhibited proper interactions with crucial amino acid residues within the active site of AR. In silico QikProp data of all hydrazones (1-15) were also determined to assess their pharmacokinetic profiles. Taken together, compound 4 stands out as a promising inhibitor of AR for further in vivo studies.

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Design, synthesis, and aldose reductase inhibitory effect of some novel carboxylic acid derivatives bearing 2-substituted-6-aryloxo-pyridazinone moiety

Cited by 28 publications

References 52 publications

Investigation of The Effect of Acylthiourea Derivatives on Diabetes‐Associated Enzymes

Investigation of The Effect of Acylthiourea Derivatives on Diabetes‐Associated Enzymes

Assessment of hypolipidemic and anti‐inflammatory properties of walnut (Juglans regia) seed coat extract and modulates some metabolic enzymes activity in triton WR‐1339‐induced hyperlipidemia in rat kidney, liver, and heart

A new series of hydrazones as small‐molecule aldose reductase inhibitors

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