Inhibition effects of quinones on aldose reductase: Antidiabetic properties

Biotech and App Biochem

Durmaz

Taslimi

et al. 2019

Self Cite

104

Aldose reductase (AR), α‐amylase, and α‐glycosidase are vital enzymes to prevent diabetic complications. Here, AR was purified from sheep kidney using elementary methods with 111.11‐purification fold and with 0.85% purification yield. The interactions between some phenolic compounds and the AR, α‐glycosidase, and α‐amylase enzyme were determined. It was found that phenolic compounds exhibit potential inhibitor properties for these enzymes. For α‐amylase, studied phenolic compounds showed IC50 values in the range of 601.56–2,067.78 nM. For α‐glycosidase, Ki values were found in the range of 169.25 ± 27.22–572.88 ± 106.76 nM. For AR, Ki values in the range of 8.48 ± 0.56–43.26 ± 7.63 µM. However, genistein showed the best inhibition effect toward AR and α‐glycosidase, but delphinidin chloride exhibited the best inhibition effect against α‐amylase enzyme. We determined that all compounds showed noncompetitive inhibition effect against AR and α‐glycosidase. Also, studied phenolic compounds may be useful in the prevention or treatment of diabetic complications.

Section: Sodium Dodecyl Sulfate-polyacrylamide Gel Electrophoresismentioning

confidence: 99%

Antidiabetic properties of dietary phenolic compounds: Inhibition effects on α‐amylase, aldose reductase, and α‐glycosidase

Biotech and App Biochem

Durmaz

Taslimi

et al. 2019

Self Cite

104

“…In this way, a disorder in any path generates an increasingly snowball effect in all metabolism. In living organisms, enzymes have a crucial role and catalyse almost all chemical reactions in metabolism . Many drugs and chemicals impact metabolism at low concentrations by increasing or decreasing regular enzyme activity, especially by inhibiting specific enzymes with critical function, and they are essential drug targets .…”

Section: Resultsmentioning

confidence: 99%

“…IC 50 values were found to be 131. 40 Figure 3). To determine K i values and inhibition types for each antihypertension drugs, Lineweaver-Burk graphs were drawn.…”

Section: Resultsmentioning

confidence: 99%

The behaviour of some antihypertension drugs on human serum paraoxonase-1: an important protector enzyme against atherosclerosis

Journal of Pharmacy and Pharmacology

2019

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Objectives Paraoxonase‐1 (PON1) enzyme is related to high‐density lipoprotein (HDL), which is calcium dependent. It has essential roles such as protecting LDL against oxidation and detoxification of highly toxic substances. It is a significant risk to reduce the levels of this enzyme in patients with diabetes mellitus, cardiovascular diseases, hyperthyroidism and chronic renal failure. Methods Here, it was reported that the purification of human serum PON1 using straightforward methods and determination of the interactions between some antihypertension drugs and the enzyme. Key finding It was found that these drugs exhibit potential inhibitor properties for human serum PON1 with IC50 values in the range of 131.40–369.40 μm and Ki values in the range of 56.24 ± 6.75–286.74 ± 28.28 μm. These drugs showed different inhibition mechanisms. It was determined that midodrine and nadolol were exhibited competitive inhibition, but atenolol and pindolol were exhibited non‐competitive inhibition. Conclusion Usage of these drugs would be hazardous in some cases.

“…This pathway metabolizes the excess glucose, resulting in adverse impacts with raised mitogen-activated protein kinase, protein kinase C, oxidative, reductive, and glycative stress, and advanced glycation end products. [1][2][3] The polyol pathway in cells consists of two main enzymes. Aldose reductase (AR) is a monomeric oxidoreductase, which causes the reduction of glucose molecule to sorbitol using NADPH.…”

Section: Introductionmentioning

confidence: 99%

Determination of the inhibition profiles of pyrazolyl–thiazole derivatives against aldose reductase and α‐glycosidase and molecular docking studies

Taslimi

Koçyiğit

et al. 2020

Archiv der Pharmazie

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Aldose reductase (AR) is the first and rate-limiting enzyme of the polyol pathway, which converts glucose to sorbitol in an NADPH-dependent reaction. α-Glycosidase breaks down starch and disaccharides to glucose. Hence, inhibition of these enzymes can be regarded a considerable approach in the treatment of diabetic complications. AR was purified from sheep liver using simple chromatographic methods. The inhibitory effects of pyrazolyl-thiazoles ((3aR,4S,7R,7aS)-2-(4-{1-[4-(4-bromophenyl) thiazol-2-yl]-5-(aryl)-4,5-dihydro-1H-pyrazol-3-yl}phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione derivatives; 3a-i) on AR and α-glycosidase enzymes were investigated. All compounds showed a good inhibitory action against AR and α-glycosidase. Among these compounds, compound 3d exhibited the best inhibition profiles against AR, with a K i value of 7.09 ± 0.19 µM, whereas compound 3e showed the lowest inhibition effects, with a K i value of 21.89 ± 1.87 µM. Also, all compounds showed efficient inhibition profiles against α-glycosidase, with K i values in the range of 0.43 ± 0.06 to 2.30 ± 0.48 µM, whereas the K i value of acarbose was 12.60 ± 0.78 µM. Lastly, molecular modeling approaches were implemented to predict the binding affinities of compounds against AR and α-glycosidase. In addition, the ADME analysis of the molecules was performed.