Scopus İndeksli Yayınlar

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Browsing Scopus İndeksli Yayınlar by Subject "Aldose reductase"

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    Evaluation of rat kidney aldose reductase inhibitory activity of some N-acetyl dehydroalanine derivatives
    (2011) Süzen, Sibel; Eczacılık Fakültesi; Daş Evci̇Men, Net; Sarikaya, Mutlu; Gürkök, Gökce
    Aldose reductase (AR) is an enzyme that catalyzes the conversion of glucose to sorbitol, which is in turn converted to fructose by sorbitol dehydrogenase. Increased AR activity has been implicated in the pathogenesis of diabetic complications such as neuropathy, nephropathy, retinopathy, and cataract. Inhibitors of AR thus seem to have the potential to prevent or treat diabetic complications. At present, however, side effects and/or insufficient pharmacokinetic profiles have made most of the drug candidates undesirable. In this study, the synthesis (l-o) and ARI activity of 15 N-acetyl dehydroalanine derivatives (a-o) are described. The synthesized compounds mainly contained aliphatic and aromatic side chains. The insertion of ethyl and chloro propyl side chains were shown to be more effective than the rest of the compounds. Between the synthesized compounds N-ethyl (b) and N-propylchloride (h) derivatives showed the best ARI activities. © 2011 Springer Science+Business Media, LLC.
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    Preliminary evaluation of rat kidney aldose reductase inhibitory activity of 2-phenylindole derivatives: Affiliation to antioxidant activity
    (2007) Süzen, Sibel; Eğitim Bilimleri Fakültesi; Evci̇Men, Net Daş; Varol, Pınar; Sarikaya, Mutlu
    Diabetic complications including nephropathy, neuropathy, and cataract are leading causes of end-stage renal diseases and neurological disorders. Aldose reductase (AR), the rate-limiting enzyme of the polyol pathway, catalyzes the reduction of glucose to sorbitol via NADPH. Excessive accumulation of intracellular sorbitol found in various tissues of diabetic animals and in cells cultured under high glucose conditions has been proposed to be an important factor for the pathogenesis of diabetic complications. Indole ring-containing AR inhibitors have received considerable attention as potential treatments for diabetic complications. However, these agents have not achieved worldwide use because of limited efficacy or unacceptable adverse effects. In this study, a series of 2-phenylindole derivatives were evaluated via an in vitro spectrophotometric assay for their ability to inhibit rat kidney AR. In addition, the antioxidant and AR inhibitory activities of the compounds under study were compared.
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    Rat lung aldose reductase inhibition capacity of substituted indole hydrazide/hydrazone derivatives
    (2012) Süzen, Sibel; Eczacılık Fakültesi; Daş Evcimen, Net; Sarikaya, Mutlu; Karaaslan, Cigdem; Yilmaz, Ayşe Didem; Shirinzadeh, Hanif
    Diabetes Mellitus is one of the most serious health problem facing both developed and developing countries. Long term complications lead to morbidity and mortality in patients with diabetes. Increased polyol pathway has been implicated in the pathogenesis of microvascular complications and cataract. Aldose reductase (AR) is the key enzyme of the polyol pathway, which converts glucose to sorbitol. Excessive accumulation of sorbitol is associated to the diabetic complications. Avoidance of sorbitol accumulation by inhibiting AR would be an efficient treatment. Due to the significance of AR as a potential drug target in the treatment of diabetic complications, there are increasing interests in the design and synthesis of AR inhibitors. In this study, 2-fluorophenylindol and 5-chloroindole hydrazide/hydrazone derivatives were tested for measuring the AR enzyme inhibitory activity. The enzyme activity was assayed by spectrophotometrically monitoring NADPH oxidation, which accompanies the reduction of D,L-glyceraldehyde used as substrate. Results showed in general 52-60 % inhibitory activity in halogen substituted indole derivatives. This study proposes a new approach for the in vitro AR inhibition activity properties and structure activity relationship of 2, 3-and 5-substituted indole ring. For the inhibitory activity, not only the indole ring is important, but also is the side chain containing the amide group and halogens.
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    Relatıonshıp between aldose reductase and superoxıde dısmutase ınhıbıtıon capacıtıes of ındole-based analogs of melatonın derıvatıves
    (2009) Süzen, Sibel; Eczacılık Fakültesi; Daş Evci̇Men, Net
    Aldose reductase (AR) has been implicated in the etiology of diabetic complications. Under diabetic conditions, the elevated vascular glucose level causes an increased flux through the polyol pathway, which induces functional and morphological changes associated with secondary diabetic complications such as cataract, neuropathy, and nephropathy. Oxidative stress, antioxidants, and the polyol pathway have recently been found to be linked in pathological states. A large number of structurally different compounds have been studied as potent in vitro AR inhibitors (ARIs). However, with few exceptions, these compounds did not show clinical benefit, and some even produced serious side effects. In view of the ARI activity of certain indole derivative compounds and antioxidant properties of melatonin, we investigated some indole-based analogs of melatonin derivatives. Antioxidant and ARI activity tests were applied to nine indole derivatives that are substituted at the third and fifth positions. Also, the relationship between ARI and antioxidant enzyme activity is discussed.
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    Screening and evaluation of rat kidney aldose reductase inhibitory activity of some pyridazine derivatives
    (2007) Süzen, Sibel; Eczacılık Fakültesi; Şüküroğlü, Mürat Kadir; Çalışkan, Burcu; Daş-Evci̇Men, Net; Sarikaya, Mutlu; Banoğlu, Erden
    Aldose reductase (AR) is an enzyme that catalyzes the conversion of glucose to sorbitol, which is in turn converted to fructose by sorbitol dehydrogenase. The increased glucose flux through this metabolic pathway has been linked to the development of diabetic complications such as neuropathy, nephropathy, retinopathy, and cataract. Inhibitors of AR thus seem to have the potential to prevent or treat diabetic complications. AR inhibitors belong to different chemical classes, one of which comprises pyridazinone analogues. At present, however, side effects and/or insufficient pharmacokinetic profiles have made most of the drug candidates undesirable. We evaluated a series of 2H-pyridazine-3-one and 6-chloropyridazine analogues via an in vitro spectrophotometric assay for their ability to inhibit rat kidney AR. The study showed that the introduction of a pyrazole ring on pyridazinone led to a marked decrease in AR inhibitory potency. Moreover, introduction of an acetic acid side chain on 2H-pyridazine-3-one and 6-chloropyridazine did not improve the AR inhibitory activity, which was an unexpected result. On the basis of preliminary AR inhibitory screening results on 2H-pyridazine-3-one and 6-chloropyridazine derivatives, we embarked on the synthesis of more derivatives to discover more active molecules.