Sürdürülebilir Kalkınma Amaçları
Yayınlar
- ArticleYalnız künye2019Anti-diabetic Properties of Calcium Channel Blockers: Inhibition Effects on Aldose Reductase Enzyme Activity
Türkeş, Cüneyt; Demir, Yeliz; Beydemir, Şükrü
Aldose reductase (AR) belongs to NADPH-dependent oxidoreductases and converts glucose to sorbitol in the polyol pathway. AR inhibition is essential to prevent diabetic complications. Here, AR was purified from sheep kidney using simple methods and determined the interactions between some calcium channel blockers and the enzyme. It was found that calcium channel blockers (cinnarizine, nilvadipine, amlodipine besylate, nifedipine, isradipine, and nitrendipine) exhibit potential inhibitor properties for sheep kidney AR with IC50 values in the range of 5.87–8.77 μM and Ki constants in the range of 2.07 ± 0.72–5.62 ± 1.53 μM. The calcium channel blockers showed different inhibition mechanisms. It was determined that all studied compounds showed competitive inhibition effect except for isradipine and nitrendipine. They showed non-competitive inhibition. Among these drugs, cinnarizine was found to be the most potent AR inhibitor (Ki: 2.07 ± 0.72 μM). They may be useful in the treatment and/or prevention of diabetic complications.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2019Synthesis, biological evaluation and in silico studies of novel N-substituted phthalazine sulfonamide compounds as potent carbonic anhydrase and acetylcholinesterase inhibitors
Türkeş, Cüneyt; Arslan, Mustafa; Demir, Yeliz; Çoçaj, Liridon; Rifati Nixha, Arleta; Beydemir, Şükrü
The synthesis, characterization and biological evaluation of a series of novel N-substituted phthalazine sulfonamide (5a-l) are disclosed. Phthalazines which are nitrogen-containing heterocyclic compounds are biologically preferential scaffolds, endowed with versatile pharmacological activity, such as anti-inflammatory, cardiotonic vasorelaxant, anticonvulsant, antihypertensive, antibacterial, anti-cancer action. The compounds were investigated for the inhibition against the cytosolic hCA I, II and AChE. Most screened sulfonamides showed high potency in inhibiting hCA II, widely involved in glaucoma, epilepsy, edema, and other pathologies (Kis in the ranging from 6.32 ± 0.06 to 128.93 ± 23.11 nM). hCA I was inhibited with Kis in the range of 6.80 ± 0.10–85.91 ± 7.57 nM, whereas AChE in the range of 60.79 ± 3.51–249.55 ± 7.89 nM. ADME prediction study of the designed N-substituted phthalazine sulfonamides showed that they are not only with carbonic anhydrase and acetylcholinesterase inhibitory activities but also with appropriate pharmacokinetic, physicochemical parameters and drug-likeness properties. Also, in silico docking studies were investigated the binding modes of selected compounds, to hCA I, II, and AChE.
RDL Kalıcı Kaydıİncele