Demir, Yeliz; Duran, Hatice Esra; Durmaz, Lokman; Taslimi, Parham; Beydemir, Şükrü; Gulçin, İlhami

Pain, as a sensible alarm signal of living organisms to avoid tissue damage, is a common and debilitating consequence of a lot of disorders and diseases. The management of chronic pain is particularly challenging. For pain treatment, many analgesic drugs are used for their therapeutic effects. In this study, some nonsteroidal anti-inflammatory drugs including etofenamate, meloxicam, diclofenac, and tenoxicam were tested against α-glycosidase from Saccharomyces cerevisiae, sorbitol dehydrogenase (SDH), and aldose reductase (AR) enzymes from sheep liver. Nonsteroidal anti-inflammatory drugs demonstrated useful inhibition properties against α-glycosidase, AR, and SDH enzymes. Ki values were found in the range of 11.93 ± 3.77–364.88 ± 40.01 μM for α-glycosidase, 3.36 ± 1.08μM–17.68 ± 3.39 mM for AR, and 1.68 ± 0.02 μM–30.98 ± 14.31 mM for SDH. They can be selective drugs as antidiabetic agents, because of their inhibitory properties against SDH, α-glycosidase, and AR enzymes.

Türkeş, Cüneyt; Beydemir, Şükrü

Drugs show their pharmacological effects by inhibiting or activating enzymes. Therefore, enzyme inhibitors have an essential place in the drug design for numerous different sorts of diseases, i.e., cardiovascular, cancer, metabolic, and neurological. The purpose of the current study was to contribute to the growing drug discovery and development area by analyzing functions and drug interactions of paraoxonase-I. For this purpose, the PON1 enzyme was purified from fresh human serum using simple, rapid, and different chromatographic techniques. Then, it was tested for the inhibitory effects of some antimycotic drugs on the PON1. Also, molecular docking analyses of each drug were carried out to determine the binding interactions on the active site of the PON1 enzyme. It was identified that the purified enzyme had the specific activity of 3880.83 EU/mg proteins and the molecular weight of 43 kDa by SDS-PAGE. IC50 values for PON1 were in the range of 0.037 ± 0.001–5.728 ± 0.043 mM. Ki constants for caspofungin acetate, amphotericin B, anidulafungin, and fluconazole were determined to be 0.0105 ± 0.0015 mM, 0.3206 ± 0.0196 mM, 0.1674 ± 0.0233 mM, and 2.5464 ± 0.1655 mM, respectively. The inhibition mechanism of amphotericin B was non-competitive, whereas anidulafungin was mixed type, and the others were competitive.

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.